WorldWideScience

Sample records for branched chain amino

  1. Branched-Chain Amino Acids

    Directory of Open Access Journals (Sweden)

    Matteo Ghiringhelli

    2015-07-01

    Full Text Available Our study is focused on evaluation and use of the most effective and correct nutrients. In particular, our attention is directed to the role of certain amino acids in cachectic patients. During parenteral nutrition in humans, physician already associates in the PN-bags different formulations including amino acids, lipids and glucose solutions or essential amino acids solution alone or exclusively branched-chain amino acids (BCAA. Studies investigated the effects of dietary BCAA ingestion on different diseases and conditions such as obesity and metabolic disorders, liver disease, muscle atrophy, cancer, impaired immunity or injuries (surgery, trauma, burns, and sepsis. BCAAs have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. Oral or parenteral administration of these three amino acids will allow us to evaluate the real efficacy of these compounds during a therapy to treat malnutrition in subjects unable to feed themselves.

  2. Branched-Chain Amino Acids.

    Science.gov (United States)

    Yamamoto, Keisuke; Tsuchisaka, Atsunari; Yukawa, Hideaki

    Branched-chain amino acids (BCAAs), viz., L-isoleucine, L-leucine, and L-valine, are essential amino acids that cannot be synthesized in higher organisms and are important nutrition for humans as well as livestock. They are also valued as synthetic intermediates for pharmaceuticals. Therefore, the demand for BCAAs in the feed and pharmaceutical industries is increasing continuously. Traditional industrial fermentative production of BCAAs was performed using microorganisms isolated by random mutagenesis. A collection of these classical strains was also scientifically useful to clarify the details of the BCAA biosynthetic pathways, which are tightly regulated by feedback inhibition and transcriptional attenuation. Based on this understanding of the metabolism of BCAAs, it is now possible for us to pursue strains with higher BCAA productivity using rational design and advanced molecular biology techniques. Additionally, systems biology approaches using augmented omics information help us to optimize carbon flux toward BCAA production. Here, we describe the biosynthetic pathways of BCAAs and their regulation and then overview the microorganisms developed for BCAA production. Other chemicals, including isobutanol, i.e., a second-generation biofuel, can be synthesized by branching the BCAA biosynthetic pathways, which are also outlined.

  3. Branched-chain amino acids for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Koretz, R L; Kjaergard, L L

    2003-01-01

    Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy....

  4. Branched chain amino acids requirements and metabolism in pigs

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham

    2015-01-01

    There is an interest to reduce the dietary crude protein (CP) level to promote the gut health of piglets, eliminate the environmental nitrogen load from intensive pig farming, and to reduce diet costs. This is possible by estimating individual amino acid (AA) requirements and by optimizing the diet...... according to the ideal protein profile that is compatible with the animal AA demand for normal body function. During the past decades, it has been tried to understand and characterize branched chain amino acids (BCAA) requirements, biological importance, and mode of actions. This is interesting for two...... of the last “-omics”, is a global analysis and interpretation of metabolome in specific health or nutritional status. Non-targeted metabolomics is used for screening the metabolic profile, and the metabolic signature could be used for hypothesis generation. The results of a non-targeted LC-MS metabolomics...

  5. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao; Saksa, Kristen; Zhao, Feiyi; Qiu, Joyce; Xiong, Liming

    2010-01-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants

  6. Branched chain amino acid profile in early chronic kidney disease

    Directory of Open Access Journals (Sweden)

    M Anil Kumar

    2012-01-01

    Full Text Available The nutritional status in chronic kidney disease (CKD patients is a predictor of prognosis during the first period of dialysis. Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid profile. Of these, the plasma levels of branched chain amino acids (BCAA, especially valine and leucine, correlate well with nutritional status. Plasma BCAAs were evaluated along with albumin and C-reactive protein in 15 patients of early stages of CKD and 15 age- and sex-matched healthy controls. A significant decrease in plasma valine, leucine and albumin levels was observed in CKD patients when compared with the controls (P <0.05. No significant difference in C-reactive protein (CRP levels was observed between the two groups. Malnutrition seen in our CKD patients in the form of hypoalbuminemia and decreased concentrations of BCAA points to the need to evaluate the nutritional status in the early stages itself. Simple measures in the form of amino acid supplementation should be instituted early to decrease the morbidity and mortality before start of dialysis in these patients.

  7. Regulation of intestinal health by branched-chain amino acids.

    Science.gov (United States)

    Zhou, Hua; Yu, Bing; Gao, Jun; Htoo, John Khun; Chen, Daiwen

    2018-01-01

    Besides its primary role in the digestion and absorption of nutrients, the intestine also interacts with a complex external milieu, and is the first defense line against noxious pathogens and antigens. Dysfunction of the intestinal barrier is associated with enhanced intestinal permeability and development of various gastrointestinal diseases. The branched-chain amino acids (BCAAs) are important nutrients, which are the essential substrates for protein biosynthesis. Recently, emerging evidence showed that BCAAs are involved in maintaining intestinal barrier function. It has been reported that dietary supplementation with BCAAs promotes intestinal development, enhances enterocyte proliferation, increases intestinal absorption of amino acids (AA) and glucose, and improves the immune defenses of piglets. The underlying mechanism of these effects is mediated by regulating expression of genes and proteins associate with various signaling pathways. In addition, BCAAs promote the production of beneficial bacteria in the intestine of mice. Compelling evidence supports the notion that BCAAs play important roles in both nutrition and intestinal health. Therefore, as functional amino acids with various physiological effects, BCAAs hold key roles in promoting intestinal development and health in animals and humans. © 2017 Japanese Society of Animal Science.

  8. Branched-chain amino acids alter neurobehavioral function in rats

    Science.gov (United States)

    Coppola, Anna; Wenner, Brett R.; Ilkayeva, Olga; Stevens, Robert D.; Maggioni, Mauro; Slotkin, Theodore A.; Levin, Edward D.

    2013-01-01

    Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders. PMID:23249694

  9. Branched-chain fatty acid biosynthesis in a branched-chain amino acid aminotransferase mutant of Staphylococcus carnosus

    DEFF Research Database (Denmark)

    Beck, Hans Christian

    2005-01-01

    Fatty acid biosynthesis by a mutant strain of Staphylococcus carnosus deficient in branched-chain amino acid aminotransferase (IlvE) activity was analysed. This mutant was unable to produce the appropriate branched-chain alpha-ketoacid precursors for branched-chain fatty acid biosynthesis from...... in rich medium and growth in defined medium supplemented with 2-methylpropanoic acid lead to extensive alteration of the fatty acid composition in the cell membrane. In rich medium, a change from 51.7% to 17.1% anteiso-C15:0, and from 3.6% to 33.9% iso-C14:0 fatty acids as compared to the wild-type strain...... for 2-methylpropanoic acid production, revealing that the IlvE protein plays an important, but not essential role in the biosynthesis of branched-chain fatty acids and secondary metabolites in S. carnosus....

  10. A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids

    OpenAIRE

    Zheng, Xiaojiao; Qiu, Yunping; Zhong, Wei; Baxter, Sarah; Su, Mingming; Li, Qiong; Xie, Guoxiang; Ore, Brandon M.; Qiao, Shanlei; Spencer, Melanie D.; Zeisel, Steven H.; Zhou, Zhanxiang; Zhao, Aihua; Jia, Wei

    2013-01-01

    Research in obesity and metabolic disorders that involve intestinal microbiota demands reliable methods for the precise measurement of the short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) concentration. Here, we report a rapid method of simultaneously determining SCFAs and BCAAs in biological samples using propyl chloroformate (PCF) derivatization followed by gas chromatography mass spectrometry (GC-MS) analysis. A one-step derivatization using 100 µL of PCF in a reactio...

  11. Branched-chain amino acids for people with hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

    2015-01-01

    -chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. SEARCH METHODS: We identified trials through...

  12. Branched-chain amino acids for people with hepatic encephalopathy

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

    2017-01-01

    -chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. Objectives: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. Search methods: We identified trials through...

  13. Branched-chain amino acids for people with hepatic encephalopathy.

    Science.gov (United States)

    Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

    2017-05-18

    Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, and LILACS (May 2017). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous

  14. Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults

    OpenAIRE

    Würtz, Peter; Soininen, Pasi; Kangas, Antti J.; Rönnemaa, Tapani; Lehtimäki, Terho; Kähönen, Mika; Viikari, Jorma S.; Raitakari, Olli T.; Ala-Korpela, Mika

    2013-01-01

    OBJECTIVE Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin resistance index in healthy young adults. RESEARCH DESIGN AND METHODS Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 y...

  15. A pilot, short-term dietary manipulation of branched chain amino acids has modest influence on fasting levels of branched chain amino acids

    OpenAIRE

    Cavallaro, Nicole Landa; Garry, Jamie; Shi, Xu; Gerszten, Robert E.; Anderson, Ellen J.; Walford, Geoffrey A.

    2016-01-01

    Background: Elevated fasting levels of branched chain amino acids (BCAAs: valine, isoleucine, leucine) in venous blood are associated with a variety of metabolic impairments, including increased risk of type 2 diabetes (T2D). Fasting BCAA levels are influenced by non-dietary factors. However, it is unknown whether fasting BCAAs can be altered through manipulation of dietary intake alone.Objective: To test whether a specific dietary intervention, using differences in BCAA intake, alters fastin...

  16. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

    Science.gov (United States)

    Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

    2004-04-01

    Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (Purea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

  17. Mathematical Modeling of the Process for Microbial Production of Branched Chained Amino Acids

    Directory of Open Access Journals (Sweden)

    Todorov K.

    2009-12-01

    Full Text Available This article deals with modelling of branched chained amino acids production. One of important branched chained amino acid is L-valine. The aim of the article is synthesis of dynamic unstructured model of fed-batch fermentation process with intensive droppings for L-valine production. The presented approach of the investigation includes the following main procedures: description of the process by generalized stoichiometric equations; preliminary data processing and calculation of specific rates for main kinetic variables; identification of the specific rates takes into account the dissolved oxygen tension; establishment and optimisation of dynamic model of the process; simulation researches. MATLAB is used as a research environment.

  18. Influence of biopolymers on the solubility of branched-chain amino acids and stability of their solutions.

    Science.gov (United States)

    Hong, Chi Rac; Lee, Gyu Whan; Paik, Hyun-Dong; Chang, Pahn-Shick; Choi, Seung Jun

    2018-01-15

    This study confirmed the possibility of biopolymer-type stabilizers to increase the saturation concentration of branched-chain amino acids by preventing their crystallization/precipitation. Although microfluidization increased the initial solubility, it failed to increase the saturation concentration of the branched-chain amino acids. The saturation concentration of the branched-chain amino acids increased from 3.81% to 4.42% and 4.85% after the incorporation of food hydrocolloids and proteins, respectively. However, the branched-chain amino acids:stabilizer ratio did not affect the solubility. In the case of food hydrocolloid-based solutions, crystal formation and growth of branched-chain amino acids occurred during storage, resulting in the precipitation of branched-chain amino acid crystals. However, food proteins effectively increased the stability of the solubilized branched-chain amino acids. The improved solubility and stability of the solubilized branched-chain amino acids could be attributed to interactions between the functional groups (carboxyl, amine, sulfate, aliphatic, aromatic, etc.) of the stabilizer and the branched-chain amino acid molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Do branched chain amino acids improve hepatic encephalopathy in cirrhosis?

    Directory of Open Access Journals (Sweden)

    Maximiliano Vergara

    2016-12-01

    Full Text Available Resumen Existe controversia sobre si los aminoácidos de cadena ramificada son efectivos para el tratamiento de la encefalopatía hepática. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos siete revisiones sistemáticas que en conjunto incluyen 32 estudios aleatorizados, de los cuales 30 responden la pregunta de este resumen. Extrajimos los resultados, realizamos un metanálisis y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los aminoácidos de cadena ramificada podrían llevar a una mejoría sintomática en la encefalopatía hepática, pero probablemente tienen poco o nulo efecto sobre la mortalidad.

  20. Whole-body nitrogen and tyrosine metabolism in surgical patients receiving branched-chain amino acid solutions

    International Nuclear Information System (INIS)

    Desai, S.P.; Bistrian, B.R.; Moldawer, L.L.; Blackburn, G.L.

    1985-01-01

    Fifteen patients undergoing gastric bypass surgery for morbid obesity received preoperatively a standard crystalline amino acid solution containing 15.6% branched-chain amino acids. During the first five postoperative days, the patients were randomized to receive one of three amino acid solutions of different branched-chain amino acid content. Whole-body amino acid appearance and oxidation were estimated using a continuous intravenous infusion of L-(U- 14 C)-tyrosine preoperatively and on the third postoperative day. This study suggests that an adequate nitrogen intake of a balanced amino acid mixture, as well as a solution enriched with branched-chain amino acids, maintains protein homeostasis and supports protein synthesis similarly in well-nourished patients following major abdominal surgery. A diet containing only branched-chain amino acids in isomolar ratios was as effective at maintaining protein retention and whole-body protein synthesis and albumin renewal postoperatively when compared with a standard amino acid formula

  1. Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

    OpenAIRE

    Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

    2010-01-01

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent obse...

  2. The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism

    OpenAIRE

    Yoon, Mee-Sup

    2016-01-01

    Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs) belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or...

  3. The Complex Role of Branched Chain Amino Acids in Diabetes and Cancer

    OpenAIRE

    O’Connell, Thomas M.

    2013-01-01

    The obesity and diabetes epidemics are continuing to spread across the globe. There is increasing evidence that diabetes leads to a significantly higher risk for certain types of cancer. Both diabetes and cancer are characterized by severe metabolic perturbations and the branched chain amino acids (BCAAs) appear to play a significant role in both of these diseases. These essential amino acids participate in a wide variety of metabolic pathways, but it is now recognized that they are also crit...

  4. Branched-chain amino acids in metabolic signaling and insulin resistance

    Science.gov (United States)

    Branched-chain amino acids (BCAAs) are important directly- and indirectly-acting nutrient signals. Frequently, their actions have been reported to be anti-obesity in nature, especially in rodent models. Yet, circulating BCAAs tend to be elevated in obesity, and even associated with poorer metaboli...

  5. Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.G.; Reily, M.D.; Lehman-McKeeman, L.D.; Vaillancourt, R.R.; Cherrington, N.J.

    2015-01-01

    Roč. 47, č. 3 (2015), s. 603-615 ISSN 0939-4451 Institutional support: RVO:60077344 Keywords : Branched chain amino acid * nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * metabolomics and transcriptomics Subject RIV: CE - Biochemistry Impact factor: 3.196, year: 2015

  6. Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes

    OpenAIRE

    Zheng, Yan; Li, Yanping; Qi, Qibin; Hruby, Adela; Manson, JoAnn E; Willett, Walter C; Wolpin, Brian M; Hu, Frank B; Qi, Lu

    2016-01-01

    Background: Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little is known about whether habitual dietary intake of BCAAs affects risk of T2D.

  7. Regulation of adipose branched chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

    Science.gov (United States)

    Elevated blood branched chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes. One possibility is that under these conditions there is a reduced cellular utilization and/or lower complete oxidation of BCAAs. White adipose tissue (WAT) has become appreciated as a...

  8. Evolution of the biosynthesis of the branched-chain amino acids

    Science.gov (United States)

    Keefe, Anthony D.; Lazcano, Antonio; Miller, Stanley L.

    1995-01-01

    The origins of the biosynthetic pathways for the branched-chain amino acids cannot be understood in terms of the backwards development of the present acetolactate pathway because it contains unstable intermediates. We propose that the first biosynthesis of the branched-chain amino acids was by the reductive carboxylation of short branched chain fatty acids giving keto acids which were then transaminated. Similar reaction sequences mediated by nonspecific enzymes would produce serine and threomine from the abundant prebiotic compounds glycolic and lactic acids. The aromatic amino acids may also have first been synthesized in this way, e.g. tryptophan from indole acetic acid. The next step would have been the biosynthesis of leucine from alpha-ketoisovalerc acid. The acetolactate pathway developed subsequently. The first version of the Krebs cycle, which was used for amino acid biosynthesis, would have been assembled by making use fo the reductive carboxylation and leucine biosynthesis enzymes, and completed with the development of a single new enzyme, succinate dehydrogenase. This evolutionary scheme suggests that there may be limitations to inferring the origins of metabolism by a simple back extrapolation of current pathways.

  9. Branched-chain amino acid supplementation and the immune response of long-distance athletes.

    Science.gov (United States)

    Bassit, Reinaldo A; Sawada, Letícia A; Bacurau, Reury F P; Navarro, Franciso; Martins, Eivor; Santos, Ronaldo V T; Caperuto, Erico C; Rogeri, Patrícia; Costa Rosa, Luís F B P

    2002-05-01

    Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.

  10. A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids.

    Science.gov (United States)

    Zheng, Xiaojiao; Qiu, Yunping; Zhong, Wei; Baxter, Sarah; Su, Mingming; Li, Qiong; Xie, Guoxiang; Ore, Brandon M; Qiao, Shanlei; Spencer, Melanie D; Zeisel, Steven H; Zhou, Zhanxiang; Zhao, Aihua; Jia, Wei

    2013-08-01

    Research in obesity and metabolic disorders that involve intestinal microbiota demands reliable methods for the precise measurement of the short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) concentration. Here, we report a rapid method of simultaneously determining SCFAs and BCAAs in biological samples using propyl chloroformate (PCF) derivatization followed by gas chromatography mass spectrometry (GC-MS) analysis. A one-step derivatization using 100 µL of PCF in a reaction system of water, propanol, and pyridine (v/v/v = 8:3:2) at pH 8 provided the optimal derivatization efficiency. The best extraction efficiency of the derivatized products was achieved by a two-step extraction with hexane. The method exhibited good derivatization efficiency and recovery for a wide range of concentrations with a low limit of detection for each compound. The relative standard deviations (RSDs) of all targeted compounds showed good intra- and inter-day (within 7 days) precision (< 10%), and good stability (< 20%) within 4 days at room temperature (23-25 °C), or 7 days when stored at -20 °C. We applied our method to measure SCFA and BCAA levels in fecal samples from rats administrated with different diet. Both univariate and multivariate statistics analysis of the concentrations of these target metabolites could differentiate three groups with ethanol intervention and different oils in diet. This method was also successfully employed to determine SCFA and BCAA in the feces, plasma and urine from normal humans, providing important baseline information of the concentrations of these metabolites. This novel metabolic profile study has great potential for translational research.

  11. Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD.

    Science.gov (United States)

    S Sonnet, Davis; N O'Leary, Monique; A Gutierrez, Mark; M Nguyen, Steven; Mateen, Samiha; Hsu, Yuehmei; P Mitchell, Kylie; J Lopez, Antonio; Vockley, Jerry; K Kennedy, Brian; Ramanathan, Arvind

    2016-07-04

    Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production.

  12. Interplay between Lipids and Branched-Chain Amino Acids in Development of Insulin Resistance

    OpenAIRE

    Newgard, Christopher B.

    2012-01-01

    Fatty acids (FA) and FA-derived metabolites have long been implicated in the development of insulin resistance and type 2 diabetes. Surprisingly, application of metabolomics technologies has revealed that branched-chain amino acids (BCAA) and related metabolites are more strongly associated with insulin resistance than many common lipid species. Moreover, the BCAA-related signature is predictive of incident diabetes and intervention outcomes, and uniquely responsive to therapeutic interventio...

  13. Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations

    OpenAIRE

    Tianlu Chen; Yan Ni; Xiaojing Ma; Yuqian Bao; Jiajian Liu; Fengjie Huang; Cheng Hu; Guoxiang Xie; Aihua Zhao; Weiping Jia; Wei Jia

    2016-01-01

    Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 C...

  14. Novel metabolic and physiological functions of branched chain amino acids: a review

    OpenAIRE

    Zhang, Shihai; Zeng, Xiangfang; Ren, Man; Mao, Xiangbing; Qiao, Shiyan

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining ...

  15. Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)

    OpenAIRE

    Lee, C. Christine; Watkins, Steve M.; Lorenzo, Carlos; Wagenknecht, Lynne E.; Il?yasova, Dora; Chen, Yii-Der I.; Haffner, Steven M.; Hanley, Anthony J.

    2016-01-01

    OBJECTIVE Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance ...

  16. Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats

    Science.gov (United States)

    Jaspers, Stephen R.; Henriksen, Erik; Jacob, Stephan; Tischler, Marc E.

    1989-01-01

    The effects of muscle unloading, adrenalectomy, and cortisol treatment on the metabolism of branched-chain amino acids in the soleus and extensor digitorum longus of tail-cast suspended rats were investigated using C-14-labeled lucine, isoleucine, and valine in incubation studies. It was found that, compared to not suspended controls, the degradation of branched-chain amino acids in hind limb muscles was accelerated in tail-cast suspended rats. Adrenalectomy was found to abolish the aminotransferase flux and to diminish the dehydrogenase flux in the soleus. The data also suggest that cortisol treatment increases the rate of metabolism of branched-chain amino acids at the dehydrogenase step.

  17. Regulation of taste-active components of meat by dietary branched-chain amino acids; effects of branched-chain amino acid antagonism.

    Science.gov (United States)

    Imanari, M; Kadowaki, M; Fujimura, S

    2008-05-01

    1. The effects of dietary branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) on taste-active components, especially free glutamate (Glu), in meat were investigated. 2. Broiler chickens (28 d old) were given varied dietary BCAA levels for 10 d before marketing. Dietary BCAA content ratios were either 100:100:100 (Low Leu group), 150:100:100 (Control group) or 150:150:150 (High Ile + Val group) for Leu:Ile:Val (% of each BCAA requirement according to NRC, 1994). Taste-related components of meat (free amino acids and ATP metabolites) and sensory scores of meat soup were estimated. 3. Free Glu content, the main taste-active component of meat, was significantly increased by dietary BCAA. Compared to the Control group, free Glu content increased by 30% in the High Ile + Val group. However, the inosine monophosphate (IMP) content in meat did not change among groups. 4. Sensory evaluation of meat soups showed that Control and High Ile + Val groups had different meat flavours. The sensory score of overall taste intensity was significantly higher in the High Ile + Val group. 5. These results suggest that dietary BCAA concentrations regulate free Glu in meat. Increasing dietary Ile + Val induces an increase in free Glu content of meat, improves meat taste and is more effective for increasing free Glu content in meat than decreasing dietary Leu level.

  18. The Complex Role of Branched Chain Amino Acids in Diabetes and Cancer

    Directory of Open Access Journals (Sweden)

    Thomas M. O'Connell

    2013-10-01

    Full Text Available The obesity and diabetes epidemics are continuing to spread across the globe. There is increasing evidence that diabetes leads to a significantly higher risk for certain types of cancer. Both diabetes and cancer are characterized by severe metabolic perturbations and the branched chain amino acids (BCAAs appear to play a significant role in both of these diseases. These essential amino acids participate in a wide variety of metabolic pathways, but it is now recognized that they are also critical regulators of a number of cell signaling pathways. An elevation in branched chain amino acids has recently been shown to be significantly correlated with insulin resistance and the future development of diabetes. In cancer, the normal demands for BCAAs are complicated by the conflicting needs of the tumor and the host. The severe muscle wasting syndrome experience by many cancer patients, known as cachexia, has motivated the use of BCAA supplementation. The desired improvement in muscle mass must be balanced by the need to avoid providing materials for tumor proliferation. A better understanding of the complex functions of BCAAs could lead to their use as biomarkers of the progression of certain cancers in diabetic patients.

  19. Interplay between lipids and branched-chain amino acids in development of insulin resistance

    Science.gov (United States)

    Newgard, Christopher B.

    2013-01-01

    Summary Fatty acids (FA) and FA-derived metabolites have long been implicated in the development of insulin resistance and type 2 diabetes. Surprisingly, application of metabolomics technologies has revealed that branched-chain amino acids (BCAA) and related metabolites are more strongly associated with insulin resistance than many common lipid species. Moreover, the BCAA-related signature is predictive of incident diabetes and intervention outcomes, and uniquely responsive to therapeutic interventions. Nevertheless, in animal feeding studies, BCAA supplementation requires the background of a high-fat diet to promote insulin resistance. This article develops a model to explain how lipids and BCAA may synergize to promote metabolic diseases. PMID:22560213

  20. Effects of Branched-chain Amino Acids on Ruminal Fermentation of Wheat Straw

    OpenAIRE

    Hui Ling Zhang; Yong Chen; Xiao Li Xu; Yu Xia Yang

    2013-01-01

    This study investigates the effects of three branched-chain amino acids (BCAA; valine, leucine, and isoleucine) on the in vitro ruminal fermentation of wheat straw using batch cultures of mixed ruminal microorganisms. BCAA were added to the buffered ruminal fluid at a concentration of 0, 2, 4, 7, or 10 mmol/L. After 72 h of anaerobic incubation, pH, volatile fatty acids (VFA), and ammonia nitrogen (NH3-N) in the ruminal fluid were determined. Dry matter (DM) and neutral detergent fiber (NDF) ...

  1. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    OpenAIRE

    Lerin, Carles; Goldfine, Allison B.; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M.; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R.; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J.; Beebe, Kirk; Gall, Walt

    2016-01-01

    Objective: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sen...

  2. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    Energy Technology Data Exchange (ETDEWEB)

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  3. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    International Nuclear Information System (INIS)

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-01-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH 4 Cl x 100 g body wt -1 x day -1 . Epitrochlearis muscles were incubated with L-[1- 14 C]-valine and L-[1- 14 C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain α-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain α-keto acid dehydrogenase

  4. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

    Directory of Open Access Journals (Sweden)

    Luigi Fontana

    2016-07-01

    Full Text Available Protein-restricted (PR, high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

  5. The effect of supplementation with branched-chain amino acids in patients with liver cirrhosis.

    Science.gov (United States)

    Urata, Yohei; Okita, Kosuke; Korenaga, Keiko; Uchida, Koichi; Yamasaki, Takahiro; Sakaida, Isao

    2007-07-01

    We investigated the effect of supplementation with branched-chain amino acids (BCAA) in patients with liver cirrhosis on the change of energy metabolism as well as glucose tolerance. Thirty liver cirrhosis patients underwent nutrient supervision by a dietician for one week. They were then prescribed oral supplementation with three packs of a BCAA nutrient (Livact 4.15 g/pack; Ajinomoto Pharma, Tokyo, Japan), taken three times a day: after breakfast, dinner and before sleep. The change in energy metabolism and glucose tolerance was examined using an indirect calorimeter and 75 g oral glucose tolerance test (75 g OGTT). Non-protein respiratory quotient (npRQ) as well as branched-chain amino acid/tyrosine ratio (BTR) showed significant improvement, especially in patients with a creatinine height index (CHI) greater than 80. There was also a significant correlation between npRQ after one week of BCAA supplementation and the CHI. The patients with CHI greater than 80 and those with borderline pattern assessed by 75 g OGTT showed significant improvement in impaired glucose tolerance. Liver cirrhosis patients with CHI greater than 80 are the first candidates for BCAA supplementation. These patients showed improvement not only in energy metabolism and BTR, but also glucose tolerance.

  6. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.

    Science.gov (United States)

    Mansfeld, Johannes; Urban, Nadine; Priebe, Steffen; Groth, Marco; Frahm, Christiane; Hartmann, Nils; Gebauer, Juliane; Ravichandran, Meenakshi; Dommaschk, Anne; Schmeisser, Sebastian; Kuhlow, Doreen; Monajembashi, Shamci; Bremer-Streck, Sibylle; Hemmerich, Peter; Kiehntopf, Michael; Zamboni, Nicola; Englert, Christoph; Guthke, Reinhard; Kaleta, Christoph; Platzer, Matthias; Sühnel, Jürgen; Witte, Otto W; Zarse, Kim; Ristow, Michael

    2015-12-01

    Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.

  7. Effects of squat exercise and branched-chain amino acid supplementation on plasma free amino acid concentrations in young women.

    Science.gov (United States)

    Shimomura, Yoshiharu; Kobayashi, Hisamine; Mawatari, Kazunori; Akita, Keiichi; Inaguma, Asami; Watanabe, Satoko; Bajotto, Gustavo; Sato, Juichi

    2009-06-01

    The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

  8. Cloning and inactivation of a branched-chain-amino-acid aminotransferase gene from Staphylococcus carnosus and characterization of the enzyme

    DEFF Research Database (Denmark)

    Madsen, Søren M; Beck, Hans Christian; Ravn, Peter

    2002-01-01

    Staphylococcus carnosus and Staphylococcus xylosus are widely used as aroma producers in the manufacture of dried fermented sausages. Catabolism of branched-chain amino acids (BCAAs) by these strains contributes to aroma formation by production of methyl-branched aldehydes and carboxy acids. The ...

  9. Effects of a branched-chain amino acid-enriched diet on chronic hepatic encephalopathy in dogs

    NARCIS (Netherlands)

    Meyer, H. P.; Chamuleau, R. A.; Legemate, D. A.; Mol, J. A.; Rothuizen, J.

    1999-01-01

    A decreased ratio of branched-chain amino acids (BCAA) to aromatic amino acids (AAA) is considered an important pathogenetic factor in hepatic encephalopathy (HE). A relationship between the deranged BCAA/AAA ratio and dopaminergic dysfunction through the formation of "false" neurotransmitters has

  10. Purification and characterization of a branched-chain amino acid aminotransferase from Lactobacillus paracasei subsp paracasei CHCC 2115

    DEFF Research Database (Denmark)

    Thage, B.V.; Rattray, F.P.; Laustsen, M.W.

    2004-01-01

    Purification and characterization of an aminotransferase (AT) specific for the degradation of branched-chain amino acids from Lactobacillus paracasei subsp. paracasei CHCC 2115. Methods and Results: The purification protocol consisted of anion exchange chromatography, affinity chromatography...... of other metal ions, thiol- and carbonyl-binding agents. The N-terminal sequence of the enzyme was SVNIDWNNLGFDYMQLPYRYVAHXKDGVXD, and had at the amino acid level, 60 and 53% identity to a branched-chain amino acid AT of Lact. plantarum and Lactococcus lactis, respectively. Conclusions: The results suggest...

  11. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

    Science.gov (United States)

    Wang, Wei; Zhang, Fuyang; Xia, Yunlong; Zhao, Shihao; Yan, Wenjun; Wang, Helin; Lee, Yan; Li, Congye; Zhang, Ling; Lian, Kun; Gao, Erhe; Cheng, Hexiang; Tao, Ling

    2016-11-01

    Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF. Copyright © 2016 the American Physiological Society.

  12. Branched-chain amino acid supplementation during bed rest: effect on recovery

    Science.gov (United States)

    Stein, T. P.; Donaldson, M. R.; Leskiw, M. J.; Schluter, M. D.; Baggett, D. W.; Boden, G.

    2003-01-01

    Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine (group 1) or with 30 mmol/day each of the three BCAAs (group 2). Whole body protein synthesis was determined with U-(15)N-labeled amino acids, muscle, and selected plasma protein synthesis with l-[(2)H(5)]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-(13)C(3)]alanine and [6,6-(2)H(2)]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 +/- 6 vs. 26 +/- 12 mg N. kg(-1). day(-1), P BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 +/- 0.066 vs. 0.088 +/- 0.12 nmol/mg protein, P BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.

  13. Branched-chain amino acid supplementation during bed rest: effect on recovery

    Science.gov (United States)

    Stein, T. P.; Donaldson, M. R.; Leskiw, M. J.; Schluter, M. D.; Baggett, D. W.; Boden, G.

    2003-01-01

    Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine (group 1) or with 30 mmol/day each of the three BCAAs (group 2). Whole body protein synthesis was determined with U-(15)N-labeled amino acids, muscle, and selected plasma protein synthesis with l-[(2)H(5)]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-(13)C(3)]alanine and [6,6-(2)H(2)]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 +/- 6 vs. 26 +/- 12 mg N. kg(-1). day(-1), P < 0.05). There was no effect of BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 +/- 0.066 vs. 0.088 +/- 0.12 nmol/mg protein, P < 0.05). Total glucose production and gluconeogenesis from alanine were unchanged with bed rest but were significantly reduced (P < 0.05) with the BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.

  14. A pilot, short-term dietary manipulation of branched chain amino acids has modest influence on fasting levels of branched chain amino acids.

    Science.gov (United States)

    Cavallaro, Nicole Landa; Garry, Jamie; Shi, Xu; Gerszten, Robert E; Anderson, Ellen J; Walford, Geoffrey A

    2016-01-01

    Elevated fasting levels of branched chain amino acids (BCAAs: valine, isoleucine, leucine) in venous blood are associated with a variety of metabolic impairments, including increased risk of type 2 diabetes (T2D). Fasting BCAA levels are influenced by non-dietary factors. However, it is unknown whether fasting BCAAs can be altered through manipulation of dietary intake alone. To test whether a specific dietary intervention, using differences in BCAA intake, alters fasting BCAA levels independent of other factors. Five healthy male volunteers underwent 4 days of a low and 4 days of a high BCAA content dietary intervention (ClinicalTrials.gov [NCT02110602]). All food and supplements were provided. Fasting BCAAs were measured from venous blood samples by mass spectrometry at baseline and after each intervention. Diets were isocaloric; contained equal percentages of calories from carbohydrate, fats, and protein; and differed from each other in BCAA content (1.5±0.1 vs. 14.0±0.6 g for valine; 4.5±0.9 g vs. 13.8±0.5 g for isoleucine; 2.1±0.2 g vs. 27.1±1.0 g for leucine; pBCAA content vs. the high BCAA content diet levels. The inter-individual response to the dietary interventions was variable and not explained by adherence. Short-term dietary manipulation of BCAA intake led to modest changes in fasting levels of BCAAs. The approach from our pilot study can be expanded to test the metabolic implications of dietary BCAA manipulation.

  15. Impact of the branched-chain amino acid to tyrosine ratio and branched-chain amino acid granule therapy in patients with hepatocellular carcinoma: A propensity score analysis.

    Science.gov (United States)

    Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Kitabatake, Shusuke; Yama, Tsuyoki

    2015-09-01

    It has been reported that the branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is a useful indicator of liver function and BCAA therapy is associated with a decreased incidence of hepatocellular carcinoma (HCC). However, there has not been sufficient research on the relationship between BTR and the effects of BCAA therapy after initial treatment of HCC. We investigated the impact of BTR and BCAA therapy on survival in patients with HCC. A total of 315 patients with HCC who were treated (n = 66) or not treated (n = 249) with BCAA were enrolled; of these, 66 were selected from each group using propensity score matching. Survival from liver-related mortality was analyzed. In patients who did not receive BCAA therapy (n = 249), multivariate analysis for factors associated with survival indicated that low BTR (≤ 4.4) was independently associated with poor prognosis in patients with HCC (hazard ratio, 1.880; 95% confidence interval, 1.125-3.143; P = 0.016). In addition, among patients selected by propensity score matching (n = 132), multivariate analysis indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio, 0.524; 95% confidence interval, 0.282-0.973; P = 0.041). BTR was not significantly associated with survival. Intervention involving BCAA therapy improved survival in patients with HCC versus untreated controls, regardless of BTR. In addition, low BTR was associated with poor prognosis in patients who did not receive BCAA therapy. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  16. A pilot, short-term dietary manipulation of branched chain amino acids has modest influence on fasting levels of branched chain amino acids

    Directory of Open Access Journals (Sweden)

    Nicole Landa Cavallaro

    2016-01-01

    Full Text Available Background: Elevated fasting levels of branched chain amino acids (BCAAs: valine, isoleucine, leucine in venous blood are associated with a variety of metabolic impairments, including increased risk of type 2 diabetes (T2D. Fasting BCAA levels are influenced by non-dietary factors. However, it is unknown whether fasting BCAAs can be altered through manipulation of dietary intake alone. Objective: To test whether a specific dietary intervention, using differences in BCAA intake, alters fasting BCAA levels independent of other factors. Design: Five healthy male volunteers underwent 4 days of a low and 4 days of a high BCAA content dietary intervention (ClinicalTrials.gov [NCT02110602]. All food and supplements were provided. Fasting BCAAs were measured from venous blood samples by mass spectrometry at baseline and after each intervention. Results: Diets were isocaloric; contained equal percentages of calories from carbohydrate, fats, and protein; and differed from each other in BCAA content (1.5±0.1 vs. 14.0±0.6 g for valine; 4.5±0.9 g vs. 13.8±0.5 g for isoleucine; 2.1±0.2 g vs. 27.1±1.0 g for leucine; p<0.0001 for all. Fasting valine was significantly lower (p=0.02 and fasting isoleucine and leucine were numerically lower following the low BCAA content vs. the high BCAA content diet levels. The inter-individual response to the dietary interventions was variable and not explained by adherence. Conclusion: Short-term dietary manipulation of BCAA intake led to modest changes in fasting levels of BCAAs. The approach from our pilot study can be expanded to test the metabolic implications of dietary BCAA manipulation.

  17. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Yukino Hatazawa

    Full Text Available Peroxisome proliferator-activated receptor (PPAR γ coactivator 1α (PGC-1α is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT 2, branched-chain α-keto acid dehydrogenase (BCKDH, which catabolize BCAA. The expression of BCKDH kinase (BCKDK, which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  18. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    Science.gov (United States)

    Hatazawa, Yukino; Tadaishi, Miki; Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

    2014-01-01

    Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  19. Branched-chain amino acids in metabolic signalling and insulin resistance

    Science.gov (United States)

    Lynch, Christopher J.; Adams, Sean H.

    2015-01-01

    Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM. PMID:25287287

  20. Branched-chain amino acid supplementation: impact on signaling and relevance to critical illness.

    Science.gov (United States)

    Mattick, John S A; Kamisoglu, Kubra; Ierapetritou, Marianthi G; Androulakis, Ioannis P; Berthiaume, Francois

    2013-01-01

    The changes that occur in mammalian systems following trauma and sepsis, termed systemic inflammatory response syndrome, elicit major changes in carbohydrate, protein, and energy metabolism. When these events persist for too long they result in a severe depletion of lean body mass, multiple organ dysfunction, and eventually death. Nutritional supplementation has been investigated to offset the severe loss of protein, and recent evidence suggests that diets enriched in branched-chain amino acids (BCAAs) may be especially beneficial. BCAAs are metabolized in two major steps that are differentially expressed in muscle and liver. In muscle, BCAAs are reversibly transaminated to the corresponding α-keto acids. For the complete degradation of BCAAs, the α-keto acids must travel to the liver to undergo oxidation. The liver, in contrast to muscle, does not significantly express the branched-chain aminotransferase. Thus, BCAA degradation is under the joint control of both liver and muscle. Recent evidence suggests that in liver, BCAAs may perform signaling functions, more specifically via activation of mTOR (mammalian target of rapamycin) signaling pathway, influencing a wide variety of metabolic and synthetic functions, including protein translation, insulin signaling, and oxidative stress following severe injury and infection. However, understanding of the system-wide effects of BCAAs that integrate both metabolic and signaling aspects is currently lacking. Further investigation in this respect will help rationalize the design and optimization of nutritional supplements containing BCAAs for critically ill patients. Copyright © 2013 Wiley Periodicals, Inc.

  1. Branched-chain amino acid supplementation promotes aerobic growth of Salmonella Typhimurium under nitrosative stress conditions.

    Science.gov (United States)

    Park, Yoon Mee; Lee, Hwa Jeong; Jeong, Jae-Ho; Kook, Joong-Ki; Choy, Hyon E; Hahn, Tae-Wook; Bang, Iel Soo

    2015-12-01

    Nitric oxide (NO) inactivates iron-sulfur enzymes in bacterial amino acid biosynthetic pathways, causing amino acid auxotrophy. We demonstrate that exogenous supplementation with branched-chain amino acids (BCAA) can restore the NO resistance of hmp mutant Salmonella Typhimurium lacking principal NO-metabolizing enzyme flavohemoglobin, and of mutants further lacking iron-sulfur enzymes dihydroxy-acid dehydratase (IlvD) and isopropylmalate isomerase (LeuCD) that are essential for BCAA biosynthesis, in an oxygen-dependent manner. BCAA supplementation did not affect the NO consumption rate of S. Typhimurium, suggesting the BCAA-promoted NO resistance independent of NO metabolism. BCAA supplementation also induced intracellular survival of ilvD and leuCD mutants at wild-type levels inside RAW 264.7 macrophages that produce constant amounts of NO regardless of varied supplemental BCAA concentrations. Our results suggest that the NO-induced BCAA auxotrophy of Salmonella, due to inactivation of iron-sulfur enzymes for BCAA biosynthesis, could be rescued by bacterial taking up exogenous BCAA available in oxic environments.

  2. Prognostic Impact of Visceral Fat Amount and Branched-Chain Amino Acids (BCAA) in Hepatocellular Carcinoma.

    Science.gov (United States)

    Higashi, Takaaki; Hayashi, Hiromitsu; Kaida, Takayoshi; Arima, Kota; Takeyama, Hideaki; Taki, Katsunobu; Izumi, Daisuke; Tokunaga, Ryuma; Kosumi, Keisuke; Nakagawa, Shigeki; Okabe, Hirohisa; Imai, Katsunobu; Nitta, Hidetoshi; Hashimoto, Daisuke; Chikamoto, Akira; Beppu, Toru; Baba, Hideo

    2015-12-01

    Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI (P BCAA levels (P BCAA, serum albumin, and prognostic nutritional index were not. High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC.

  3. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao

    2010-08-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

  4. Study on color identification for monitoring and controlling fermentation process of branched chain amino acid

    Science.gov (United States)

    Ma, Lei; Wang, Yizhong; Chen, Ning; Liu, Tiegen; Xu, Qingyang; Kong, Fanzhi

    2008-12-01

    In this paper, a new method for monitoring and controlling fermentation process of branched chain amino acid (BCAA) was proposed based on color identification. The color image of fermentation broth of BCAA was firstly taken by a CCD camera. Then, it was changed from RGB color model to HIS color model. Its histograms of hue H and saturation S were calculated, which were used as the input of a designed BP network. The output of the BP network was the description of the color of fermentation broth of BCAA. After training, the color of fermentation broth was identified by the BP network according to the histograms of H and S of a fermentation broth image. Along with other parameters, the fermentation process of BCAA was monitored and controlled to start the stationary phase of fermentation soon. Experiments were conducted with satisfied results to show the feasibility and usefulness of color identification of fermentation broth in fermentation process control of BCAA.

  5. Branched Chain Amino Acid Oxidation in Cultured Rat Skeletal Muscle Cells

    Science.gov (United States)

    Pardridge, William M.; Casanello-Ertl, Delia; Duducgian-Vartavarian, Luiza

    1980-01-01

    Leucine metabolism in skeletal muscle is linked to protein turnover. Since clofibrate is known both to cause myopathy and to decrease muscle protein content, the present investigations were designed to examine the effects of acute clofibrate treatment on leucine oxidation. Rat skeletal muscle cells in tissue culture were used in these studies because cultivated skeletal muscle cells, like muscle in vivo, have been shown to actively utilize branched chain amino acids and to produce alanine. The conversion of [1-14C]leucine to 14CO2 or to the [1-14C]keto-acid of leucine (α-keto-isocaproate) was linear for at least 2 h of incubation; the production of 14CO2 from [1-14C]leucine was saturable with a Km = 6.3 mM and a maximum oxidation rate (Vmax) = 31 nmol/mg protein per 120 min. Clofibric acid selectively inhibited the oxidation of [1-14C]leucine (Ki = 0.85 mM) and [U-14C]isoleucine, but had no effect on the oxidation of [U-14C]glutamate, -alanine, -lactate, or -palmitate. The inhibition of [1-14C]leucine oxidation by clofibrate was also observed in the rat quarter-diaphragm preparation. Clofibrate primarily inhibited the production of 14CO2 and had relatively little effect on the production of [1-14C]keto-acid of leucine. A physiological concentration—3.0 g/100 ml—of albumin, which actively binds clofibric acid, inhibited but did not abolish the effects of a 2-mM concentration of clofibric acid on leucine oxidation. Clofibrate treatment stimulated the net consumption of pyruvate, and inhibited the net production of alanine. The drug also increased the cytosolic NADH/NAD+ ratio as reflected by an increase in the lactate/pyruvate ratio, in association with a decrease in cell aspartate levels. The changes in pyruvate metabolism and cell redox state induced by the drug were delayed compared with the nearly immediate inhibition of leucine oxidation. These studies suggest that clofibric acid, in concentrations that approximate high therapeutic levels of the drug

  6. Diabetes and branched-chain amino acids: What is the link?

    Science.gov (United States)

    Bloomgarden, Zachary

    2018-05-01

    Branched-chain amino acids (BCAA) have increasingly been studied as playing a role in diabetes, with the PubMed search string "diabetes" AND "branched chain amino acids" showing particular growth in studies of the topic over the past decade (Fig. ). In the Young Finn's Study, BCAA and, to a lesser extent, the aromatic amino acids phenylalanine and tyrosine were associated with insulin resistance (IR) in men but not in women, whereas the gluconeogenic amino acids alanine, glutamine, or glycine, and several other amino acids (i.e. histidine, arginine, and tryptophan) did not show an association with IR. Obesity may track more strongly than metabolic syndrome and diabetes with elevated BCAA. In a study of 1302 people aged 40-79; higher levels of BCAA tracked with older age, male sex, and metabolic syndrome, as well as with obesity, cardiovascular risk, dyslipidemia, hypertension, and uric acid. Medium- and long-chain acylcarnitines, by-products of mitochondrial catabolism of BCAAs, as well as branched-chain keto acids and the BCAA themselves distinguished obese people having versus not having features of IR, and in a study of 898 patients with essential hypertension, the BCAA and tyrosine and phenylalanine were associated with metabolic syndrome and impaired fasting glucose. In a meta-analysis of three genome-wide association studies, elevations in BCAA and, to a lesser extent, in alanine tracked with IR, whereas higher levels of glutamine and glycine were associated with lesser likelihood of IR. Given these associations with IR, it is not surprising that a number of studies have shown higher BCAA levels in people with and prior to development of type 2 diabetes (T2D), although this has particularly been shown in Caucasian and Asian ethnic groups while not appearing to occur in African Americans. Similarly, higher BCAA levels track with cardiovascular disease. [Figure: see text] The metabolism of BCAA involves two processes: (i) a reversible process catalysed by a

  7. Impact of Branched-Chain Amino Acid Catabolism on Fatty Acid and Alkene Biosynthesis in Micrococcus luteus.

    Science.gov (United States)

    Surger, Maximilian J; Angelov, Angel; Stier, Philipp; Übelacker, Maria; Liebl, Wolfgang

    2018-01-01

    Micrococcus luteus naturally produces alkenes, unsaturated aliphatic hydrocarbons, and represents a promising host to produce hydrocarbons as constituents of biofuels and lubricants. In this work, we identify the genes for key enzymes of the branched-chain amino acid catabolism in M. luteus , whose first metabolic steps lead also to the formation of primer molecules for branched-chain fatty acid and olefin biosynthesis, and demonstrate how these genes can be used to manipulate the production of specific olefins in this organism. We constructed mutants of several gene candidates involved in the branched-chain amino acid metabolism or its regulation and investigated the resulting changes in the cellular fatty acid and olefin profiles by GC/MS. The gene cluster encoding the components of the branched-chain α-keto acid dehydrogenase (BCKD) complex was identified by deletion and promoter exchange mutagenesis. Overexpression of the BCKD gene cluster resulted in about threefold increased olefin production whereas deletion of the cluster led to a drastic reduction in branched-chain fatty acid content and a complete loss of olefin production. The specificities of the acyl-CoA dehydrogenases of the branched amino acid degradation pathways were deduced from the fatty acid and olefin profiles of the respective deletion mutant strains. In addition, growth experiments with branched amino acids as the only nitrogen source were carried out with the mutants in order to confirm our annotations. Both the deletion mutant of the BCKD complex, responsible for the further degradation of all three branched-chain amino acids, as well as the deletion mutant of the proposed isovaleryl-CoA dehydrogenase (specific for leucine degradation) were not able to grow on leucine in contrast to the parental strain. In conclusion, our experiments allow the unambigous assignment of specific functions to the genes for key enzymes of the branched-chain amino acid metabolism of M. luteus . We also show how

  8. Novel metabolic and physiological functions of branched chain amino acids: a review

    Institute of Scientific and Technical Information of China (English)

    Shihai Zhang; Xiangfang Zeng; Man Ren; Xiangbing Mao; Shiyan Qiao

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans.BCAA (isoleucine,leucine and valine) regulate many key signaling pathways,the most classic of which is the activation of the mTOR signaling pathway.This signaling pathway connects many diverse physiological and metabolic roles.Recent years have witnessed many striking developments in determining the novel functions of BCAA including:(1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis.(2) BCAA,especially isoleucine,play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters.(3)Supplementation of leucine in the diet enhances meat quality in finishing pigs.(4) BCAA are beneficial for mammary health,milk quality and embryo growth.(5) BCAA enhance intestinal development,intestinal amino acid transportation and mucin production.(6) BCAA participate in up-regulating innate and adaptive immune responses.In addition,abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity,diabetes and other metabolic diseases.This review will provide some insights into these novel metabolic and physiological functions of BCAA.

  9. Novel metabolic and physiological functions of branched chain amino acids: a review.

    Science.gov (United States)

    Zhang, Shihai; Zeng, Xiangfang; Ren, Man; Mao, Xiangbing; Qiao, Shiyan

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

  10. Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

    Science.gov (United States)

    Stein, T. P.; Schluter, M. D.; Leskiw, M. J.; Boden, G.

    1999-01-01

    Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P BCAA supplementation attenuates the N loss during short-term bed rest.

  11. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  12. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Full Text Available Objective: Plasma levels of branched-chain amino acids (BCAA are consistently elevated in obesity and type 2 diabetes (T2D and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28. We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. Keywords: Insulin sensitivity, BCAA, Fatty acid oxidation, TCA cycle

  13. The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism

    Directory of Open Access Journals (Sweden)

    Mee-Sup Yoon

    2016-07-01

    Full Text Available Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or type 2 diabetes mellitus (T2DM. The activation of mammalian target of rapamycin complex 1 (mTORC1 by BCAAs has been suggested to cause insulin resistance. In addition, defective BCAA oxidative metabolism might occur in obesity, leading to a further accumulation of BCAAs and toxic intermediates. This review provides the current understanding of the mechanism of BCAA-induced mTORC1 activation, as well as the effect of mTOR activation on metabolic health in terms of insulin sensitivity. Furthermore, the effects of impaired BCAA metabolism will be discussed in detail.

  14. Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

    Science.gov (United States)

    Stein, T. P.; Schluter, M. D.; Leskiw, M. J.; Boden, G.

    1999-01-01

    Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest.

  15. Effects of Branched-chain Amino Acids on In vitro Ruminal Fermentation of Wheat Straw

    Science.gov (United States)

    Zhang, Hui Ling; Chen, Yong; Xu, Xiao Li; Yang, Yu Xia

    2013-01-01

    This study investigates the effects of three branched-chain amino acids (BCAA; valine, leucine, and isoleucine) on the in vitro ruminal fermentation of wheat straw using batch cultures of mixed ruminal microorganisms. BCAA were added to the buffered ruminal fluid at a concentration of 0, 2, 4, 7, or 10 mmol/L. After 72 h of anaerobic incubation, pH, volatile fatty acids (VFA), and ammonia nitrogen (NH3-N) in the ruminal fluid were determined. Dry matter (DM) and neutral detergent fiber (NDF) degradability were calculated after determining the DM and NDF in the original material and in the residue after incubation. The addition of valine, leucine, or isoleucine increased the total VFA yields (p≤0.001). However, the total VFA yields did not increase with the increase of BCAA supplement level. Total branched-chain VFA yields linearly increased as the supplemental amount of BCAA increased (p<0.001). The molar proportions of acetate and propionate decreased, whereas that of butyrate increased with the addition of valine and isoleucine (p<0.05). Moreover, the proportions of propionate and butyrate decreased (p<0.01) with the addition of leucine. Meanwhile, the molar proportions of isobutyrate were increased and linearly decreased (p<0.001) by valine and leucine, respectively. The addition of leucine or isoleucine resulted in a linear (p<0.001) increase in the molar proportions of isovalerate. The degradability of NDF achieved the maximum when valine or isoleucine was added at 2 mmol/L. The results suggest that low concentrations of BCAA (2 mmol/L) allow more efficient regulation of ruminal fermentation in vitro, as indicated by higher VFA yield and NDF degradability. Therefore, the optimum initial dose of BCAA for in vitro ruminal fermentation is 2 mmol/L. PMID:25049818

  16. Effects of Branched-chain Amino Acids on Ruminal Fermentation of Wheat Straw

    Directory of Open Access Journals (Sweden)

    Hui Ling Zhang

    2013-04-01

    Full Text Available This study investigates the effects of three branched-chain amino acids (BCAA; valine, leucine, and isoleucine on the in vitro ruminal fermentation of wheat straw using batch cultures of mixed ruminal microorganisms. BCAA were added to the buffered ruminal fluid at a concentration of 0, 2, 4, 7, or 10 mmol/L. After 72 h of anaerobic incubation, pH, volatile fatty acids (VFA, and ammonia nitrogen (NH3-N in the ruminal fluid were determined. Dry matter (DM and neutral detergent fiber (NDF degradability were calculated after determining the DM and NDF in the original material and in the residue after incubation. The addition of valine, leucine, or isoleucine increased the total VFA yields (p≤0.001. However, the total VFA yields did not increase with the increase of BCAA supplement level. Total branched-chain VFA yields linearly increased as the supplemental amount of BCAA increased (p<0.001. The molar proportions of acetate and propionate decreased, whereas that of butyrate increased with the addition of valine and isoleucine (p<0.05. Moreover, the proportions of propionate and butyrate decreased (p<0.01 with the addition of leucine. Meanwhile, the molar proportions of isobutyrate were increased and linearly decreased (p<0.001 by valine and leucine, respectively. The addition of leucine or isoleucine resulted in a linear (p<0.001 increase in the molar proportions of isovalerate. The degradability of NDF achieved the maximum when valine or isoleucine was added at 2 mmol/L. The results suggest that low concentrations of BCAA (2 mmol/L allow more efficient regulation of ruminal fermentation in vitro, as indicated by higher VFA yield and NDF degradability. Therefore, the optimum initial dose of BCAA for in vitro ruminal fermentation is 2 mmol/L.

  17. Clofibric acid stimulates branched-chain amino acid catabolism by three mechanisms.

    Science.gov (United States)

    Kobayashi, Rumi; Murakami, Taro; Obayashi, Mariko; Nakai, Naoya; Jaskiewicz, Jerzy; Fujiwara, Yoko; Shimomura, Yoshiharu; Harris, Robert A

    2002-11-15

    Clofibrate promotes catabolism of branched-chain amino acids by increasing the activity of the branched-chain alpha-keto acid dehydrogenase [BCKDH] complex. Depending upon the sex of the rats, nutritional state, and tissue being studied, clofibrate can affect BCKDH complex activity by three different mechanisms. First, by directly inhibiting BCKDH kinase activity, clofibrate can increase the proportion of the BCKDH complex in the active, dephosphorylated state. This occurs in situations in which the BCKDH complex is largely inactive due to phosphorylation, e.g., in the skeletal muscle of chow-fed rats or in the liver of female rats late in the light cycle. Second, by increasing the levels at which the enzyme components of the BCKDH complex are expressed, clofibrate can increase the total enzymatic activity of the BCKDH complex. This is readily demonstrated in livers of rats fed a low-protein diet, a nutritional condition that induces a decrease in the level of expression of the BCKDH complex. Third, by decreasing the amount of BCKDH kinase expressed and therefore its activity, clofibrate induces an increase in the percentage of the BCKDH complex in the active, dephosphorylated state. This occurs in the livers of rats fed a low-protein diet, a nutritional condition that causes inactivation of the BCKDH complex due to upregulation of the amount of BCKDH kinase. WY-14,643, which, like clofibric acid, is a ligand for the peroxisome-proliferator-activated receptor alpha [PPARalpha], does not directly inhibit BCKDH kinase but produces the same long-term effects as clofibrate on expression of the BCKDH complex and its kinase. Thus, clofibrate is unique in its capacity to stimulate BCAA oxidation through inhibition of BCKDH kinase activity, whereas PPARalpha activators in general promote BCAA oxidation by increasing expression of components of the BCKDH complex and decreasing expression of the BCKDH kinase.

  18. Higher concentrations of branched-chain amino acids in breast milk of obese mothers.

    Science.gov (United States)

    De Luca, Arnaud; Hankard, Régis; Alexandre-Gouabau, Marie-Cécile; Ferchaud-Roucher, Véronique; Darmaun, Dominique; Boquien, Clair-Yves

    2016-01-01

    Nutrition during fetal life and early childhood is thought to play a crucial role in the risk for developing metabolic syndrome and cardiovascular diseases in the future adult and branched-chain amino acids (BCAA) intake may play a role in the development of obesity. The aim of this study was to compare the breast milk amino acid profiles of obese and normal weight (control) breast-feeding mothers. Fifty obese and 50 control breast-feeding mothers were enrolled. Age and parity were similar in both groups. Breast milk samples were collected at the end of the first month of lactation. Free amino acid (FAA) concentrations in breast milk were determined by ultra-performance liquid chromatography tandem mass spectrometry. Comparisons between groups were performed using a two-tailed paired t test. We analyzed 45 breast milk samples from each group. Body mass index was 34.3 ± 3.9 kg/m(2) in the obese group and 21.6 ± 1.4 kg/m(2) in the control group (P milk of obese mothers (95.5 ± 38.2 μM versus 79.8 ± 30.9 μM; P = 0.037), as was tyrosine concentration (13.8 ± 7.1 μM versus 10.6 ± 5.2 μM; P = 0.016). The mature breast milk of obese mothers contained 20% more BCAA and 30% more tyrosine than breast milk of control mothers. Whether altered breast milk FAA profile affects metabolic risk in the breast-fed child remains to be explored. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

    OpenAIRE

    Yunxia Liu; Weibing Dong; Jing Shao; Yibin Wang; Meiyi Zhou; Haipeng Sun

    2017-01-01

    Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively cont...

  20. Associations among circulating branched-chain amino acids and tyrosine with muscle volume and glucose metabolism in individuals without diabetes

    OpenAIRE

    Honda, Tatsuro

    2016-01-01

    Background and Aims: Amino acid metabolites including branched chain amino acids (BCAA) and tyrosine (Tyr) affect glucose metabolism. The effects of BCAA on insulin resistance in patients with diabetes seem to conflict with mechanisms determined in animal models and cultured cells. We investigated the physiological effects of BCAA and Tyr on glucose metabolism among healthy community dwellers to clarify the controversy surrounding the effects of BCAA. Participant and methods: We investigated ...

  1. Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km

    DEFF Research Database (Denmark)

    Madsen, Klavs; MacLean, David A; Kiens, Bente

    1996-01-01

    This study was undertaken to determine the effects of ingesting either glucose (trial G) or glucose plus branched-chain amino acids (BCAA: trial B), compared with placebo (trial P), during prolonged exercise. Nine well-trained cyclists with a maximal oxygen uptake of 63.1 +/- 1.5 ml O2. min-1.kg-...

  2. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis

    DEFF Research Database (Denmark)

    Vilstrup, Hendrik; Gluud, C; Hardt, F

    1990-01-01

    We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients...

  3. Branched-chain amino acids enhance cyst development in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Yamamoto, Junya; Nishio, Saori; Hattanda, Fumihiko; Nakazawa, Daigo; Kimura, Toru; Sata, Michio; Makita, Minoru; Ishikawa, Yasunobu; Atsumi, Tatsuya

    2017-08-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1 flox/flox :Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age. The BCAA group showed significantly greater kidney/body weight ratio and higher cystic index in both the kidney and liver compared to the placebo-treated mice. We found that the L-type amino acid transporter 1 that facilitates BCAA entry into cells is strongly expressed in cells lining the cysts. We also found increased cyst-lining cell proliferation and upregulation of mTOR and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways in the BCAA group. In vitro, we cultured renal epithelial cell lines from Pkd1 null mice with or without leucine. Leucine was found to stimulate cell proliferation, as well as activate mTOR and MAPK/ERK pathways in these cells. Thus, BCAA accelerated disease progression by mTOR and MAPK/ERK pathways. Hence, BCAA may be harmful to patients with ADPKD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    Science.gov (United States)

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  5. Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

    Science.gov (United States)

    Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

    2014-01-01

    Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Branched-chain amino acids and ammonia metabolism in liver disease: therapeutic implications.

    Science.gov (United States)

    Holecek, Milan

    2013-10-01

    The rationale for recommendation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in treatment of liver failure is based on their unique pharmacologic properties, stimulatory effect on ammonia detoxification to glutamine (GLN), and decreased concentrations in liver cirrhosis. Multiple lines of evidence have shown that the main cause of the BCAA deficiency in liver cirrhosis is their consumption in skeletal muscle for synthesis of glutamate, which acts as a substrate for ammonia detoxification to GLN and that the BCAA administration to patients with liver failure may exert a number of positive effects that may be more pronounced in patients with marked depression of BCAA levels. On the other hand, due to the stimulatory effect of BCAA on GLN synthesis, BCAA supplementation may lead to enhanced ammonia production from GLN breakdown in the intestine and the kidneys and thus exert harmful effects on the development of hepatic encephalopathy. Therefore, to enhance therapeutic effectiveness of the BCAA in patients with liver injury, their detrimental effect on ammonia production, which is negligible in healthy people and/or patients with other disorders, should be avoided. In treatment of hepatic encephalopathy, simultaneous administration of the BCAA (to correct amino acid imbalance and promote ammonia detoxification to GLN) with α-ketoglutarate (to inhibit GLN breakdown to ammonia in enterocytes) and/or phenylbutyrate (to enhance GLN excretion by the kidneys) is suggested. Attention should be given to the type of liver injury, gastrointestinal bleeding, signs of inflammation, and the dose of BCAA. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Efficacy, Dosage, and Duration of Action of Branched Chain Amino Acid Therapy for Traumatic Brain Injury

    Science.gov (United States)

    Elkind, Jaclynn A.; Lim, Miranda M.; Johnson, Brian N.; Palmer, Chris P.; Putnam, Brendan J.; Kirschen, Matthew P.; Cohen, Akiva S.

    2015-01-01

    Traumatic brain injury (TBI) results in long-lasting cognitive impairments for which there is currently no accepted treatment. A well-established mouse model of mild to moderate TBI, lateral fluid percussion injury (FPI), shows changes in network excitability in the hippocampus including a decrease in net synaptic efficacy in area CA1 and an increase in net synaptic efficacy in dentate gyrus. Previous studies identified a novel therapy consisting of branched chain amino acids (BCAAs), which restored normal mouse hippocampal responses and ameliorated cognitive impairment following FPI. However, the optimal BCAA dose and length of treatment needed to improve cognitive recovery is unknown. In the current study, mice underwent FPI then consumed 100 mM BCAA supplemented water ad libitum for 2, 3, 4, 5, and 10 days. BCAA therapy ameliorated cognitive impairment at 5 and 10 days duration. Neither BCAA supplementation at 50 mM nor BCAAs when dosed 5 days on then 5 days off was sufficient to ameliorate cognitive impairment. These results suggest that brain injury causes alterations in hippocampal function, which underlie and contribute to hippocampal cognitive impairment, which are reversible with at least 5 days of BCAA treatment, and that sustaining this effect is dependent on continuous treatment. Our findings have profound implications for the clinical investigation of TBI therapy. PMID:25870584

  8. Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids.

    Science.gov (United States)

    Gojda, Jan; Straková, Radka; Plíhalová, Andrea; Tůma, Petr; Potočková, Jana; Polák, Jan; Anděl, Michal

    2017-01-01

    Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p BCAA tests with no change in the placebo group. An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent. © 2017 S. Karger AG, Basel.

  9. Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

    Science.gov (United States)

    Nakamura, Ikuo

    2014-01-01

    It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article. PMID:24966600

  10. Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations

    Science.gov (United States)

    Chen, Tianlu; Ni, Yan; Ma, Xiaojing; Bao, Yuqian; Liu, Jiajian; Huang, Fengjie; Hu, Cheng; Xie, Guoxiang; Zhao, Aihua; Jia, Weiping; Jia, Wei

    2016-01-01

    Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 Chinese participants at different stages of diabetes development, using an ultra-performance liquid chromatography triple quadruple mass spectrometry platform. The alterations of the five AAs in Chinese populations are well in accordance with previous reports. Early elevation of the five AAs and their combined score was closely associated with future development of diabetes, suggesting an important role of these metabolites as early markers of diabetes. On the other hand, the five AAs were not as good as existing clinical markers in differentiating diabetic patients from their healthy counterparts. Our findings verified the close correlation of BCAAs and AAAs with insulin resistance and future development of diabetes in Chinese populations and highlighted the predictive value of these markers for future development of diabetes. PMID:26846565

  11. Efficacy, dosage and duration of action of branched chain amino acid therapy for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jaclynn eElkind

    2015-03-01

    Full Text Available Traumatic brain injury (TBI results in long-lasting cognitive impairments for which there is currently no accepted treatment. A well-established mouse model of mild to moderate TBI, lateral fluid percussion injury (FPI, shows changes in network excitability in the hippocampus including a decrease in net synaptic efficacy in area CA1 and an increase in net synaptic efficacy in dentate gyrus. Previous studies identified a novel therapy consisting of branched chain amino acids (BCAAs which restored normal mouse hippocampal responses and ameliorated cognitive impairment following FPI. However, the optimal BCAA dose and length of treatment needed to improve cognitive recovery is unknown. In the current study mice underwent FPI then consumed 100 mM BCAA supplemented water ad libitum for 2, 3, 4, 5 and 10 days. BCAA therapy ameliorated cognitive impairment at 5 and 10 days duration. Neither BCAA supplementation at 50 mM, nor BCAAs when dosed 5 days on then 5 days off, was sufficient to ameliorate cognitive impairment. These results suggest that brain injury causes alterations in hippocampal function which underlie and contribute to hippocampal cognitive impairment which are reversible with at least 5 days of BCAA treatment, and that sustaining this effect is dependent on continuous treatment. Our findings have profound implications for the clinical investigation of TBI therapy.

  12. Branched-chain Amino Acid Biosensing Using Fluorescent Modified Engineered Leucine/Isoleucine/Valine Binding Protein

    Directory of Open Access Journals (Sweden)

    Koji Sode

    2007-06-01

    Full Text Available A novel fluorescence sensing system for branched-chain amino acids (BCAAswas developed based on engineered leucine/isoleucine/valine-binding proteins (LIVBPsconjugated with environmentally sensitive fluorescence probes. LIVBP was cloned fromEscherichia coli and Gln149Cys, Gly227Cys, and Gln254Cys mutants were generated bygenetic engineering. The mutant LIVBPs were then modified with environmentallysensitive fluorophores. Based on the fluorescence intensity change observed upon thebinding of the ligands, the MIANS-conjugated Gln149Cys mutant (Gln149Cys-M showedthe highest and most sensitive response. The BCAAs Leu, Ile, and Val can each bemonitored at the sub-micromolar level using Gln149Cys-M. Measurements were alsocarried out on a mixture of BCAFAs and revealed that Gln149Cys-M-based measurementis not significantly affected by the change in the molar ratio of Leu, Ile and Val in thesample. Its high sensitivity and group-specific molecular recognition ability make the newsensing system ideally suited for the measurement of BCAAs and the determination of theFischer ratio, an indicator of hepatic disease involving metabolic dysfunction.

  13. Effects of infusion of branched chain amino-acids enriched TPN solutions on plasma amino-acid profiles in sepsis and trauma patients

    NARCIS (Netherlands)

    Vente, J. P.; von Meyenfeldt, M. F.; van Eijk, H. M.; van Berlo, C. L.; Gouma, D. J.; van der Linden, C. J.; Soeters, P. B.

    1990-01-01

    Total parenteral nutrition with branched chain amino-acids enriched solutions has been advocated in patients with sepsis and stress because of favourable effects on nitrogen balance, protein synthesis and immune competence. The rationale for the use of BCAA-enriched solutions is based on their

  14. Inflammation and ER Stress Regulate Branched-Chain Amino Acid Uptake and Metabolism in Adipocytes

    Science.gov (United States)

    Burrill, Joel S.; Long, Eric K.; Reilly, Brian; Deng, Yingfeng; Armitage, Ian M.; Scherer, Philipp E.

    2015-01-01

    Inflammation plays a critical role in the pathology of obesity-linked insulin resistance and is mechanistically linked to the effects of macrophage-derived cytokines on adipocyte energy metabolism, particularly that of the mitochondrial branched-chain amino acid (BCAA) and tricarboxylic acid (TCA) pathways. To address the role of inflammation on energy metabolism in adipocytes, we used high fat-fed C57BL/6J mice and lean controls and measured the down-regulation of genes linked to BCAA and TCA cycle metabolism selectively in visceral but not in subcutaneous adipose tissue, brown fat, liver, or muscle. Using 3T3-L1 cells, TNFα, and other proinflammatory cytokine treatments reduced the expression of the genes linked to BCAA transport and oxidation. Consistent with this, [14C]-leucine uptake and conversion to triglycerides was markedly attenuated in TNFα-treated adipocytes, whereas the conversion to protein was relatively unaffected. Because inflammatory cytokines lead to the induction of endoplasmic reticulum stress, we evaluated the effects of tunicamycin or thapsigargin treatment of 3T3-L1 cells and measured a similar down-regulation in the BCAA/TCA cycle pathway. Moreover, transgenic mice overexpressing X-box binding protein 1 in adipocytes similarly down-regulated genes of BCAA and TCA metabolism in vivo. These results indicate that inflammation and endoplasmic reticulum stress attenuate lipogenesis in visceral adipose depots by down-regulating the BCAA/TCA metabolism pathway and are consistent with a model whereby the accumulation of serum BCAA in the obese insulin-resistant state is linked to adipose inflammation. PMID:25635940

  15. Comparative Genomics of Regulation of Fatty Acid and Branched-chain Amino Acid Utilization in Proteobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Kazakov, Alexey E.; Rodionov, Dmitry A.; Arkin, Adam Paul; Dubchak, Inna; Gelfand, Mikhail S.; Alm, Eric

    2008-10-31

    Bacteria can use branched-chain amino acids (ILV, i.e. isoleucine, leucine, valine) and fatty acids (FA) as sole carbon and energy sources convering ILV into acetyl-CoA, propanoyl-CoA and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR and GntR families binding to eleven distinct DNA motifs. The ILV degradation genes in gamma- and beta-proteobacteria are mainly regulated by anovel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species), in addition, the TetR-type regulator LiuQ was identified in some beta-proteobacteria (8 species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in the Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gamma-proteobacteria (34 species), PsrA in gamma- and beta-proteobacteria (45 species), FadP in beta-proteobacteria (14 species), and LiuR orthologs in alpha-proteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from the functional and evolutionary points of view.

  16. The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population.

    Science.gov (United States)

    Yang, Panpan; Hu, Wen; Fu, Zhenzhen; Sun, Luning; Zhou, Ying; Gong, Yingyun; Yang, Tao; Zhou, Hongwen

    2016-07-25

    It has been suggested that serum branched-chain amino acids (BCAAs) are associated with the incident, progression and prognostic of type 2 diabetes. However, the role of BCAAs in metabolic dyslipidemia (raised triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C)) remains poorly understood. This study aims to investigate 1) the association of serum BCAAs with total cholesterol (TC), TG, HDL-C and low-density lipoprotein cholesterol (LDL-C) and 2) the association between serum BCAAs levels and risk of metabolic dyslipidemia in a community population with different glucose homeostasis. Demographics data and blood samples were collected from 2251 Chinese subjects from the Huaian Diabetes Protective Program (HADPP) study. After exclusion for cardiovascular disease (CVD), serious hepatic or nephritic diseases and others, 1320 subjects remained for analysis (789 subjects with hemoglobin A1c (HbA1c) > 5.7, 521 with HbA1c ≤ 5.7). Serum BCAAs level was measured by liquid chromatography-tandem mass spectrometry (LC MS/MS). The association of BCAAs with lipids or with the risk of metabolic dyslipidemia was analyzed. Elevated serum BCAAs (both total and individual BCAA) were positively associated with TG and inversely associated with HDL-C in the whole population. These correlations were still significant even after adjustment for confounding factors (r = 0.165, p dyslipidemia was 3.703 (2.261, 6.065) and 3.702 (1.877, 7.304), respectively (all p dyslipidemia. In addition, glucose homeostasis could play a certain role in BCAAs-related dyslipidemia.

  17. Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis following Resistance Exercise in Humans

    Directory of Open Access Journals (Sweden)

    Sarah R. Jackman

    2017-06-01

    Full Text Available The ingestion of intact protein or essential amino acids (EAA stimulates mechanistic target of rapamycin complex-1 (mTORC1 signaling and muscle protein synthesis (MPS following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients following resistance exercise in humans. Ten young (20.1 ± 1.3 years, resistance-trained men completed two trials, ingesting either 5.6 g BCAA or a placebo (PLA drink immediately after resistance exercise. Myofibrillar-MPS was measured during exercise recovery with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre and 4 h-post drink ingestion. Blood samples were collected at time-points before and after drink ingestion. Western blotting was used to measure the phosphorylation status of mTORC1 signaling proteins in biopsies collected pre, 1-, and 4 h-post drink. The percentage increase from baseline in plasma leucine (300 ± 96%, isoleucine (300 ± 88%, and valine (144 ± 59% concentrations peaked 0.5 h-post drink in BCAA. A greater phosphorylation status of S6K1Thr389 (P = 0.017 and PRAS40 (P = 0.037 was observed in BCAA than PLA at 1 h-post drink ingestion. Myofibrillar-MPS was 22% higher (P = 0.012 in BCAA (0.110 ± 0.009%/h than PLA (0.090 ± 0.006%/h. Phenylalanine Ra was ~6% lower in BCAA (18.00 ± 4.31 μmol·kgBM−1 than PLA (21.75 ± 4.89 μmol·kgBM−1; P = 0.028 after drink ingestion. We conclude that ingesting BCAAs alone increases the post-exercise stimulation of myofibrillar-MPS and phosphorylation status mTORC1 signaling.

  18. Branched-Chain Amino Acids Are Required for the Survival and Virulence of Actinobacillus pleuropneumoniae in Swine▿

    OpenAIRE

    Subashchandrabose, Sargurunathan; LeVeque, Rhiannon M.; Wagner, Trevor K.; Kirkwood, Roy N.; Kiupel, Matti; Mulks, Martha H.

    2009-01-01

    In Actinobacillus pleuropneumoniae, which causes porcine pleuropneumonia, ilvI was identified as an in vivo-induced (ivi) gene and encodes the enzyme acetohydroxyacid synthase (AHAS) required for branched-chain amino acid (BCAA) biosynthesis. ilvI and 7 of 32 additional ivi promoters were upregulated in vitro when grown in chemically defined medium (CDM) lacking BCAA. Based on these observations, we hypothesized that BCAA would be found at limiting concentrations in pulmonary secretions and t...

  19. Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

    OpenAIRE

    Darren G. Candow; Scott C. Forbes; Jonathan P. Little; Ralph J. Manders

    2012-01-01

    The loss of muscle mass and strength with aging (i.e., sarcopenia) has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA), primarily leucine, increases the activation of pathways involved in muscl...

  20. Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease

    OpenAIRE

    Sunny, Nishanth E.; Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J.; Nautiyal, Manisha; Mathew, Justin T.; Williams, Caroline M.; Cusi, Kenneth

    2015-01-01

    Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperin...

  1. Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes

    OpenAIRE

    Katagiri, Ryoko; Goto, Atsushi; Budhathoki, Sanjeev; Yamaji, Taiki; Yamamoto, Hiroshi; Kato, Yumiko; Iwasaki, Motoki; Tsugane, Shoichiro

    2018-01-01

    Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-α [TNF-α]) concentratio...

  2. Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

    OpenAIRE

    Urho M Kujala; Markku Peltonen; Merja K. Laine; Merja K. Laine; Jaakko Kaprio; Jaakko Kaprio; Jaakko Kaprio; Olli. J. Heinonen; Jouko Sundvall; Johan G. Eriksson; Johan G. Eriksson; Johan G. Eriksson; Antti Jula; Seppo Sarna; Heikki Kainulainen

    2016-01-01

    Aims/hypothesis Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid (TCA) cycle, intramyocellular lipid storage and oxidation thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed wheth...

  3. Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise

    DEFF Research Database (Denmark)

    Moberg, Marcus; Apró, William; Ekblom, Björn

    2016-01-01

    Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution...... of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo...

  4. Interactions among the branched-chain amino acids and their effects on methionine utilization in growing pigs: effects on plasma amino- and keto-acid concentrations and branched-chain keto-acid dehydrogenase activity.

    Science.gov (United States)

    Langer, S; Scislowski, P W; Brown, D S; Dewey, P; Fuller, M F

    2000-01-01

    The present experiment was designed to elucidate the mechanism of the methionine-sparing effect of excess branched-chain amino acids (BCAA) reported in the previous paper (Langer & Fuller, 2000). Twelve growing gilts (30-35 kg) were prepared with arterial catheters. After recovery, they received for 7 d a semipurified diet with a balanced amino acid pattern. On the 7th day blood samples were taken before (16 h postabsorptive) and after the morning meal (4 h postprandial). The animals were then divided into three groups and received for a further 7 d a methionine-limiting diet (80% of requirement) (1) without any amino acid excess; (2) with excess leucine (50% over requirement); or (3) with excesses of all three BCAA (leucine, isoleucine, valine, each 50% over the requirement). On the 7th day blood samples were taken as in the first period, after which the animals were killed and liver and muscle samples taken. Plasma amino acid and branched-chain keto acid (BCKA) concentrations in the blood and branched-chain keto-acid dehydrogenase (BCKDH; EC 1.2.4.4) activity in liver and muscle homogenates were determined. Compared with those on the balanced diet, pigs fed on methionine-limiting diets had significantly lower (P < 0.05) plasma methionine concentrations in the postprandial but not in the postabsorptive state. There was no effect of either leucine or a mixture of all three BCAA fed in excess on plasma methionine concentrations. Excess dietary leucine reduced (P < 0.05) the plasma concentrations of isoleucine and valine in both the postprandial and postabsorptive states. Plasma concentrations of the BCKA reflected the changes in the corresponding amino acids. Basal BCKDH activity in the liver and total BCKDH activity in the biceps femoris muscle were significantly (P < 0.05) increased by excesses of leucine or all BCAA.

  5. Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution

    DEFF Research Database (Denmark)

    Maida, Adriano; Chan, Jessica S K; Sjøberg, Kim Anker

    2017-01-01

    OBJECTIVE: Dietary protein dilution (PD) has been associated with metabolic advantages such as improved glucose homeostasis and increased energy expenditure. This phenotype involves liver-induced release of FGF21 in response to amino acid insufficiency; however, it has remained unclear whether...... dietary dilution of specific amino acids (AAs) is also required. Circulating branched chain amino acids (BCAAs) are sensitive to protein intake, elevated in the serum of obese humans and mice and thought to promote insulin resistance. We tested whether replenishment of dietary BCAAs to an AA-diluted (AAD......) diet is sufficient to reverse the glucoregulatory benefits of dietary PD. METHODS: We conducted AA profiling of serum from healthy humans and lean and high fat-fed or New Zealand obese (NZO) mice following dietary PD. We fed wildtype and NZO mice one of three amino acid defined diets: control, total...

  6. Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial.

    Science.gov (United States)

    Fouré, Alexandre; Nosaka, Kazunori; Gastaldi, Marguerite; Mattei, Jean-Pierre; Boudinet, Hélène; Guye, Maxime; Vilmen, Christophe; Le Fur, Yann; Bendahan, David; Gondin, Julien

    2016-02-01

    Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  7. Associations between plasma branched-chain amino acids, β-aminoisobutyric acid and body composition.

    Science.gov (United States)

    Rietman, Annemarie; Stanley, Takara L; Clish, Clary; Mootha, Vamsi; Mensink, Marco; Grinspoon, Steven K; Makimura, Hideo

    2016-01-01

    Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 (se 0·08) (×10(7)) v. 1·3 (se 0·06) (×10(7)) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT (R 0·49; P = 0·0006) and trended to an association with SAT (R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling (P BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R -0·50, P = 0·0004; glucose AUC: R 0·53, P BCAA were not associated with B-AIBA (R -0·04; P = 0·79). B-AIBA was negatively associated with SAT (R -0·37; P = 0·01) but only trended to an association with VAT (R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling (P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R -0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance.

  8. Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

    Science.gov (United States)

    Ji, L L; Miller, R H; Nagle, F J; Lardy, H A; Stratman, F W

    1987-08-01

    The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

  9. Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Kayo Ikeda

    2017-11-01

    Full Text Available Summary: Foxp3+ regulatory T (Treg cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs, including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3+ Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp3+ Treg cells showed impaired in vivo replication and decreased numbers of Treg cells. Slc3a2-deficient Treg cells showed impaired isoleucine-induced activation of the mTORC1 pathway and an altered metabolic state. Slc3a2 mutant mice did not show an isoleucine-induced increase of Treg cells in vivo and exhibited multi-organ inflammation. Taken together, these findings demonstrate that BCAA controls Treg cell maintenance via Slc3a2-dependent metabolic regulation. : Treg cells regulate excess immune responses and are highly proliferative in vivo. Ikeda et al. find that branched-chain amino acids (BCAAs are essentially required to maintain expansion and the suppressive capacity of Treg cells via Slc3a2 and mTORC1. Keywords: Treg cells, amino acids, immunometabolism, immune regulation, transporter

  10. Aspectos atuais sobre aminoácidos de cadeia ramificada e exercício físico Current aspects of branched chain amino acid and exercise

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Rogero

    2008-12-01

    Full Text Available Em humanos saudáveis, nove aminoácidos são considerados essenciais, uma vez que não podem ser sintetizados endogenamente e, portanto, devem ser ingeridos por meio da dieta. Dentre os aminoácidos essenciais, se incluem os três aminoácidos de cadeia ramificada, ou seja, leucina, valina e isoleucina. Esses aminoácidos participam da regulação do balanço protéico corporal além de serem fonte de nitrogênio para a síntese de alanina e glutamina. No tocante à regulação da síntese protéica muscular, verifica-se que a leucina age estimulando a fase de iniciação da tradução do RNA-mensageiro em proteína, por mecanismos tanto dependentes quanto independentes de insulina. No que concerne ao exercício físico, supõe-se que esses aminoácidos estejam envolvidos na fadiga central, no balanço protéico muscular, na secreção de insulina, na modulação da imunocompetência, no aumento da performance de indivíduos que se exercitam em ambientes quentes e na diminuição do grau de lesão muscular. Nesse contexto, essa revisão aborda os aspectos atuais do metabolismo e da suplementação de aminoácidos de cadeia ramificada no exercício físico.In healthy humans, nine amino acids are considered to be essential once they cannot be endogenously synthesised and must therefore be ingested in the diet. Amongst the essential amino acids are the three branched chain amino acids, namely, leucine, valine and isoleucine. These amino acids participate in the regulation of protein balance in addition to being nitrogen sources for the synthesis of alanine and glutamine. As to the regulation of muscle protein synthesis, leucine acts in the stimulation of initiation of mRNA translation into protein, both through mechanisms that are dependent and independent of insulin. In the physiology of physical exercise, these branched amino acids play a role in central fatigue hypothesis, in muscle protein balance, in the secretion of insulin, in the

  11. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

    Science.gov (United States)

    Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

    2017-05-01

    Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION

  12. Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells.

    Science.gov (United States)

    Lu, Gang; Sun, Haipeng; She, Pengxiang; Youn, Ji-Youn; Warburton, Sarah; Ping, Peipei; Vondriska, Thomas M; Cai, Hua; Lynch, Christopher J; Wang, Yibin

    2009-06-01

    The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibition of the branched-chain-alpha-ketoacid dehydrogenase (BCKD) complex, the rate-limiting step in their metabolism. BCKD is inhibited by phosphorylation of its E1alpha subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates. Loss of PP2Cm completely abolished substrate-induced E1alpha dephosphorylation both in vitro and in vivo. PP2Cm-deficient mice exhibited BCAA catabolic defects and a metabolic phenotype similar to the intermittent or intermediate types of human maple syrup urine disease (MSUD), a hereditary disorder caused by defects in BCKD activity. These results indicate that PP2Cm is the endogenous BCKD phosphatase required for nutrient-mediated regulation of BCKD activity and suggest that defects in PP2Cm may be responsible for a subset of human MSUD.

  13. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Directory of Open Access Journals (Sweden)

    Roze Ludmila V

    2010-08-01

    Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

  14. Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

    Directory of Open Access Journals (Sweden)

    Darren G. Candow

    2012-11-01

    Full Text Available The loss of muscle mass and strength with aging (i.e., sarcopenia has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA, primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis.

  15. Identification of branched-chain amino acid aminotransferases active towards (R)-(+)-1-phenylethylamine among PLP fold type IV transaminases.

    Science.gov (United States)

    Bezsudnova, Ekaterina Yu; Dibrova, Daria V; Nikolaeva, Alena Yu; Rakitina, Tatiana V; Popov, Vladimir O

    2018-04-10

    New class IV transaminases with activity towards L-Leu, which is typical of branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)-(+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)-amine:pyruvate transaminases, were identified by bioinformatics analysis, obtained in recombinant form, and analyzed. The values of catalytic activities in the reaction with L-Leu and (R)-PEA are comparable to those measured for characteristic transaminases with the corresponding specificity. Earlier, (R)-selective class IV transaminases were found to be active, apart from (R)-PEA, only with some other (R)-primary amines and D-amino acids. Sequences encoding new transaminases with mixed type of activity were found by searching for changes in the conserved motifs of sequences of BCAT by different bioinformatics tools. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

    Science.gov (United States)

    Barceló, Antonia; Morell-Garcia, Daniel; Salord, Neus; Esquinas, Cristina; Pérez, Gerardo; Pérez, Antonio; Monasterio, Carmen; Gasa, Merce; Fortuna, Ana Maria; Montserrat, Josep Maria; Mayos, Mercedes

    2017-12-01

    There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea. © 2017 European Sleep Research Society.

  17. Transamination of branched chain amino acids (BCAA) in rat adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Frick, G.P.; Goodman, H.M.

    1986-03-05

    Like most extrahepatic tissues, adipose tissue can transaminate the BCAA faster than they are oxidized. Catabolism of the BCAA by adipose tissue appears to be limited by the activity of branched chain ..cap alpha..-keto acid dehydrogenase (BCDH). Conditions which stimulate the activity of this intramitochondrial enzyme in tissue extracts also increase the rate at which (1-/sup 14/C)leucine (L) and (1-/sup 14/C)valine (V) are oxidized by tissue segments. However, when maximum rates of oxidation were measured, 10 mM L was oxidized to /sup 14/CO/sub 2/ 5 times faster than 10 mM V (30 +/- 2 vs. 6 +/- 1 nmol min/sup -1/ g tis/sup -1/). In contrast, the ..cap alpha..-keto analogs of L and V were oxidized by tissue segments at nearly equal rates which slightly exceeded the rate of L oxidation. These results suggested that transamination might limit the catabolism of V, perhaps due to its inaccessibility to transaminase. The distribution of transaminase activity in tissue extracts was determined after centrifugation to obtain mitochondrial and cytosolic fractions. L and V were transaminated at similar rates by enzymes in both fractions. Transaminase activity in the mitochondrial fraction was greater than that of the cytosol and exceeded the capacity of the tissue to oxidize L. Catabolism of BCAA may depend upon intramitochondrial transamination and oxidation of V may be slower than that of L because uptake of V by mitochondria may be slower than that of L.

  18. Transamination of branched chain amino acids (BCAA) in rat adipose tissue

    International Nuclear Information System (INIS)

    Frick, G.P.; Goodman, H.M.

    1986-01-01

    Like most extrahepatic tissues, adipose tissue can transaminate the BCAA faster than they are oxidized. Catabolism of the BCAA by adipose tissue appears to be limited by the activity of branched chain α-keto acid dehydrogenase (BCDH). Conditions which stimulate the activity of this intramitochondrial enzyme in tissue extracts also increase the rate at which [1- 14 C]leucine (L) and [1- 14 C]valine (V) are oxidized by tissue segments. However, when maximum rates of oxidation were measured, 10 mM L was oxidized to 14 CO 2 5 times faster than 10 mM V (30 +/- 2 vs. 6 +/- 1 nmol min -1 g tis -1 ). In contrast, the α-keto analogs of L and V were oxidized by tissue segments at nearly equal rates which slightly exceeded the rate of L oxidation. These results suggested that transamination might limit the catabolism of V, perhaps due to its inaccessibility to transaminase. The distribution of transaminase activity in tissue extracts was determined after centrifugation to obtain mitochondrial and cytosolic fractions. L and V were transaminated at similar rates by enzymes in both fractions. Transaminase activity in the mitochondrial fraction was greater than that of the cytosol and exceeded the capacity of the tissue to oxidize L. Catabolism of BCAA may depend upon intramitochondrial transamination and oxidation of V may be slower than that of L because uptake of V by mitochondria may be slower than that of L

  19. Metabolic reconstructions identify plant 3-methylglutaconyl-CoA hydratase that is crucial for branched-chain amino acid catabolism in mitochondria

    Science.gov (United States)

    The proteinogenic branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are essential nutrients for mammals. In plants, they double as alternative energy sources when carbohydrates become limiting, the catabolism of BCAAs providing electrons to the respiratory chain and intermediates...

  20. Branched-chain amino acid (BCAA) supplementation enhances adaptability to exercise training of mice with a muscle-specific defect in the control of BCAA catabolism.

    Science.gov (United States)

    Xu, Minjun; Kitaura, Yasuyuki; Shindo, Daichi; Shimomura, Yoshiharu

    2018-03-01

    Branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BDK) suppresses the branched-chain amino acid (BCAA) catabolism by inactivation of the BCKDH complex. The muscle-specific BDK-deficient (BDK-mKO) mice showed accelerated BCAA oxidation in muscle and decreased endurance capacity after training (Xu et al. PLoS One. 12 (2017) e0180989). We here report that BCAA supplementation overcompensated endurance capacity in BDK-mKO mice after training.

  1. Color identification and fuzzy reasoning based monitoring and controlling of fermentation process of branched chain amino acid

    Science.gov (United States)

    Ma, Lei; Wang, Yizhong; Xu, Qingyang; Huang, Huafang; Zhang, Rui; Chen, Ning

    2009-11-01

    The main production method of branched chain amino acid (BCAA) is microbial fermentation. In this paper, to monitor and to control the fermentation process of BCAA, especially its logarithmic phase, parameters such as the color of fermentation broth, culture temperature, pH, revolution, dissolved oxygen, airflow rate, pressure, optical density, and residual glucose, are measured and/or controlled and/or adjusted. The color of fermentation broth is measured using the HIS color model and a BP neural network. The network's input is the histograms of hue H and saturation S, and output is the color description. Fermentation process parameters are adjusted using fuzzy reasoning, which is performed by inference rules. According to the practical situation of BCAA fermentation process, all parameters are divided into four grades, and different fuzzy rules are established.

  2. Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Raaymakers, J S; Saris, W H

    1995-01-01

    1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched-chain amino acids (BCAAs......) affect performance. Ten endurance-trained male athletes were studied during cycle exercise at 70-75% maximal power output, while ingesting, ad random and double-blind, drinks that contained 6% sucrose (control) or 6% sucrose supplemented with (1) tryptophan (3 g l-1), (2) a low dose of BCAA (6 g l-1...... tryptophan ingestion caused a 7- to 20-fold increase. Exercise time to exhaustion was not different between treatments (122 +/- 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise...

  3. Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

    Directory of Open Access Journals (Sweden)

    da Luz Claudia R

    2011-12-01

    Full Text Available Abstract Branched-chain amino acids (BCAA supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE-derived biochemical markers of muscle soreness (creatine kinase (CK, aldolase, myoglobin, soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

  4. Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Humberto Nicastro

    2012-01-01

    Full Text Available Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs, especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

  5. Branched-Chain Amino Acids Are the Primary Limiting Amino Acids in the Diets of Endurance-Trained Men after a Bout of Prolonged Exercise.

    Science.gov (United States)

    Kato, Hiroyuki; Suzuki, Katsuya; Bannai, Makoto; Moore, Daniel R

    2018-05-09

    The indicator amino acid oxidation (IAAO) method estimates the protein intake required to maximize whole-body protein synthesis and identify the daily protein requirement in a variety of populations. However, it is unclear whether the greater requirements for endurance athletes previously determined by the IAAO reflect an increased demand for all or only some amino acids. The aim of this study was to determine the primary rate-limiting amino acids in endurance-trained athletes after prolonged exercise, by measuring the oxidation of ingested [1-13C]phenylalanine in response to variable amino acid intake. Five endurance-trained men (means ± SDs: age, 26 ± 7 y; body weight, 66.9 ± 9.5 kg; maximal oxygen consumption, 63.3 ± 4.3 mL · kg-1 · min-1) performed 5 trials that involved 2 d of controlled diet (1.4 g protein · kg-1 · d-1) and running (10 km on day 1 and 5 km on day 2) prior to performing an acute bout of endurance exercise (20-km treadmill run) on day 3. During recovery on day 3, participants consumed test diets as 8 isocaloric hourly meals providing sufficient energy and carbohydrate but a variable amino acid intake. The test diets, consumed in random order, were deficient (BASE: 0.8 g · kg-1 · d-1) and sufficient (SUF; 1.75 g · kg-1 · d-1) amino acid diets modeled after egg protein, and BASE supplemented with branched-chain amino acids (BCAA diet; 1.03 g · kg-1 · d-1), essential amino acids (EAA diet; 1.23 g · kg-1 · d-1), or nonessential amino acids (NEAA diet; 1.75 g · kg-1 · d-1). Whole-body phenylalanine flux (Q), 13CO2 excretion (F13CO2), and phenylalanine oxidation (OX) were determined according to standard IAAO methodology. There was no effect of amino acid intake on Q (P = 0.43). F13CO2 was significantly (all P amino acids in the greater daily protein requirement of endurance trained men. This trial was registered at clinicaltrial.gov as NCT02628249.

  6. Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Scott B Crown

    Full Text Available The branched chain amino acids (BCAA valine, leucine and isoleucine have been implicated in a number of diseases including obesity, insulin resistance, and type 2 diabetes mellitus, although the mechanisms are still poorly understood. Adipose tissue plays an important role in BCAA homeostasis by actively metabolizing circulating BCAA. In this work, we have investigated the link between BCAA catabolism and fatty acid synthesis in 3T3-L1 adipocytes using parallel 13C-labeling experiments, mass spectrometry and model-based isotopomer data analysis. Specifically, we performed parallel labeling experiments with four fully 13C-labeled tracers, [U-13C]valine, [U-13C]leucine, [U-13C]isoleucine and [U-13C]glutamine. We measured mass isotopomer distributions of fatty acids and intracellular metabolites by GC-MS and analyzed the data using the isotopomer spectral analysis (ISA framework. We demonstrate that 3T3-L1 adipocytes accumulate significant amounts of even chain length (C14:0, C16:0 and C18:0 and odd chain length (C15:0 and C17:0 fatty acids under standard cell culture conditions. Using a novel GC-MS method, we demonstrate that propionyl-CoA acts as the primer on fatty acid synthase for the production of odd chain fatty acids. BCAA contributed significantly to the production of all fatty acids. Leucine and isoleucine contributed at least 25% to lipogenic acetyl-CoA pool, and valine and isoleucine contributed 100% to lipogenic propionyl-CoA pool. Our results further suggest that low activity of methylmalonyl-CoA mutase and mass action kinetics of propionyl-CoA on fatty acid synthase result in high rates of odd chain fatty acid synthesis in 3T3-L1 cells. Overall, this work provides important new insights into the connection between BCAA catabolism and fatty acid synthesis in adipocytes and underscores the high capacity of adipocytes for metabolizing BCAA.

  7. Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Sunny, Nishanth E; Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J; Nautiyal, Manisha; Mathew, Justin T; Williams, Caroline M; Cusi, Kenneth

    2015-08-15

    Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperinsulinemic clamps (insulin stimulation) were measured in 94 human subjects with varying degrees of insulin sensitivity to identify their relationships with insulin resistance. Furthermore, the impact of elevated BCAA on hepatic TCA cycle was determined in a diet-induced mouse model of NAFLD, utilizing targeted metabolomics and nuclear magnetic resonance (NMR)-based metabolic flux analysis. Insulin stimulation revealed robust relationships between human plasma BCAA and indices of insulin resistance, indicating chronic metabolic overload from BCAA. Human plasma BCAA and long-chain acylcarnitines also showed a positive correlation, suggesting modulation of mitochondrial metabolism by BCAA. Concurrently, mice with NAFLD failed to optimally induce hepatic mTORC1, plasma ketones, and hepatic long-chain acylcarnitines, following acute elevation of plasma BCAA. Furthermore, elevated BCAA failed to induce multiple fluxes through hepatic TCA cycle in mice with NAFLD. Our data suggest that BCAA are essential to mediate efficient channeling of carbon substrates for oxidation through mitochondrial TCA cycle. Impairment of BCAA-mediated upregulation of the TCA cycle could be a significant contributor to mitochondrial dysfunction in NAFLD.

  8. Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

    Science.gov (United States)

    Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2017-04-01

    Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

  9. Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

    Science.gov (United States)

    Liu, Yunxia; Dong, Weibing; Shao, Jing; Wang, Yibin; Zhou, Meiyi; Sun, Haipeng

    2017-01-01

    Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

  10. Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

    Directory of Open Access Journals (Sweden)

    Yunxia Liu

    2017-10-01

    Full Text Available Recent studies have linked branched-chain amino acid (BCAA with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15 is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

  11. A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Martina Goffredo

    2017-06-01

    Full Text Available Dysregulation of several metabolite pathways, including branched-chain amino acids (BCAAs, are associated with Non-Alcoholic Fatty Liver Disease (NAFLD and insulin resistance in adults, while studies in youth reported conflicting results. We explored whether, independently of obesity and insulin resistance, obese adolescents with NAFLD display a metabolomic signature consistent with disturbances in amino acid and lipid metabolism. A total of 180 plasma metabolites were measured by a targeted metabolomic approach in 78 obese adolescents with (n = 30 or without (n = 48 NAFLD assessed by magnetic resonance imaging (MRI. All subjects underwent an oral glucose tolerance test and subsets of patients underwent a two-step hyperinsulinemic-euglycemic clamp and/or a second MRI after a 2.2 ± 0.8-year follow-up. Adolescents with NAFLD had higher plasma levels of valine (p = 0.02, isoleucine (p = 0.03, tryptophan (p = 0.02, and lysine (p = 0.02 after adjustment for confounding factors. Circulating BCAAs were negatively correlated with peripheral and hepatic insulin sensitivity. Furthermore, higher baseline valine levels predicted an increase in hepatic fat content (HFF at follow-up (p = 0.01. These results indicate that a dysregulation of BCAA metabolism characterizes obese adolescents with NAFLD independently of obesity and insulin resistance and predict an increase in hepatic fat content over time.

  12. Isolation and Characterization of a Gene Specific to Lager Brewing Yeast That Encodes a Branched-Chain Amino Acid Permease

    Science.gov (United States)

    Kodama, Yukiko; Omura, Fumihiko; Ashikari, Toshihiko

    2001-01-01

    We found two types of branched-chain amino acid permease gene (BAP2) in the lager brewing yeast Saccharomyces pastorianus BH-225 and cloned one type of BAP2 gene (Lg-BAP2), which is identical to that of Saccharomyces bayanus (by-BAP2-1). The other BAP2 gene of the lager brewing yeast (cer-BAP2) is very similar to the Saccharomyces cerevisiae BAP2 gene. This result substantiates the notion that lager brewing yeast is a hybrid of S. cerevisiae and S. bayanus. The amino acid sequence homology between S. cerevisiae Bap2p and Lg-Bap2p was 88%. The transcription of Lg-BAP2 was not induced by the addition of leucine to the growth medium, while that of cer-BAP2 was induced. The transcription of Lg-BAP2 was repressed by the presence of ethanol and weak organic acid, while that of cer-BAP2 was not affected by these compounds. Furthermore, Northern analysis during beer fermentation revealed that the transcription of Lg-BAP2 was repressed at the beginning of the fermentation, while cer-BAP2 was highly expressed throughout the fermentation. These results suggest that the transcription of Lg-BAP2 is regulated differently from that of cer-BAP2 in lager brewing yeasts. PMID:11472919

  13. Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia

    OpenAIRE

    Ottosson, Filip; Ericson, Ulrika; Almgren, Peter; Nilsson, Jeanette; Magnusson, Martin; Fernandez, Céline; Melander, Olle

    2016-01-01

    High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover desig...

  14. Branched-Chain Amino and Keto Acid Biochemistry and Cellular Biology in Central Nervous System Diseases

    Science.gov (United States)

    2009-05-21

    proceeded through the BCKDC, they result in ubiquitously produced small molecules involved in various metabolic pathways, such as gluconeogenesis ...I. Nissim, L. Hertz, Precursors of glutamic acid nitrogen in primary neuronal cultures: studies with 15N, Neurochem Res 15 (1990) 1191-1196. 35...amino acid transamination. J Neurochem 66(1):378-85. Yudkoff M, Nissim I, Hertz L. 1990. Precursors of glutamic acid nitrogen in primary neuronal

  15. Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.

    Science.gov (United States)

    Wubetu, Gizachew Yismaw; Utsunomiya, Tohru; Ishikawa, Daichi; Ikemoto, Tetsuya; Yamada, Shinichiro; Morine, Yuji; Iwahashi, Shuichi; Saito, Yu; Arakawa, Yusuke; Imura, Satoru; Arimochi, Hideki; Shimada, Mitsuo

    2014-09-01

    Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise.

    Science.gov (United States)

    Moberg, Marcus; Apró, William; Ekblom, Björn; van Hall, Gerrit; Holmberg, Hans-Christer; Blomstrand, Eva

    2016-06-01

    Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo, leucine, BCAA, or EAA (including the BCAA) in random order. Muscle biopsies were taken at rest, immediately after exercise, and following 90 and 180 min of recovery. Following 90 min of recovery the activity of S6 kinase 1 (S6K1) was greater than at rest in all four trials (PlaceboBCAABCAA. However, after 180 min of recovery this difference between EAA and BCAA had disappeared, although with both these supplements the increases were still higher than with leucine (40%, P BCAA. Copyright © 2016 the American Physiological Society.

  17. Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

    Science.gov (United States)

    Gojda, J; Rossmeislová, L; Straková, R; Tůmová, J; Elkalaf, M; Jaček, M; Tůma, P; Potočková, J; Krauzová, E; Waldauf, P; Trnka, J; Štich, V; Anděl, M

    2017-05-01

    Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3-0 months: -1.64 [-2.5; -0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

  18. Rapid and Precise Measurement of Serum Branched-Chain and Aromatic Amino Acids by Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry

    OpenAIRE

    Yang, Ruiyue; Dong, Jun; Guo, Hanbang; Li, Hongxia; Wang, Shu; Zhao, Haijian; Zhou, Weiyan; Yu, Songlin; Wang, Mo; Chen, Wenxiang

    2013-01-01

    BACKGROUND: Serum branched-chain and aromatic amino acids (BCAAs and AAAs) have emerged as predictors for the future development of diabetes and may aid in diabetes risk assessment. However, the current methods for the analysis of such amino acids in biological samples are time consuming. METHODS: An isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) method for serum BCAAs and AAAs was developed. The serum was mixed with isotope-labeled BCAA and AAA internal standar...

  19. Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial

    NARCIS (Netherlands)

    von Meyenfeldt, M. F.; Soeters, P. B.; Vente, J. P.; van Berlo, C. L.; Rouflart, M. M.; de Jong, K. P.; van der Linden, C. J.; Gouma, D. J.

    1990-01-01

    Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double

  20. Prospective randomized double-blind trial of branched chain amino acid enriched versus standard parenteral nutrition solutions in traumatized and septic patients

    NARCIS (Netherlands)

    Vente, J. P.; Soeters, P. B.; von Meyenfeldt, M. F.; Rouflart, M. M.; van der Linden, C. J.; Gouma, D. J.

    1991-01-01

    The addition of branched chain amino acids (BCAA) to total parenteral nutrition (TPN) solutions of balanced aminoacid composition has been reported to result in improved nitrogen balance, preservation of plasma protein levels, and improved immune function; however, only a few large clinical studies

  1. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance

    NARCIS (Netherlands)

    Connelly, Margery A.; Wolak-Dinsmore, Justyna; Dullaart, Robin P. F.

    Background: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the

  2. Effect of a high-protein, high-fiber diet plus supplementation with branched-chain amino acids on the nutritional status of patients with cirrhosis

    Directory of Open Access Journals (Sweden)

    A. Ruiz-Margáin

    2018-01-01

    Conclusion: Supplementation with branched-chain amino acids plus a high-fiber, high-protein diet is a safe intervention in patients with cirrhosis. It helps increase muscle mass and does not raise the levels of ammonia or glucose, nor is it associated with the development of hepatic encephalopathy.

  3. Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord

    2011-01-01

    Branched-chain amino acids (BCAA) are used in attempts to reduce blood ammonia in patients with cirrhosis and intermittent hepatic encephalopathy based on the hypothesis that BCAA stimulate muscle ammonia detoxification. We studied the effects of an oral dose of BCAA on the skeletal muscle...

  4. Nontargeted LC–MS Metabolomics Approach for Metabolic Profiling of Plasma and Urine from Pigs Fed Branched Chain Amino Acids for Maximum Growth Performance

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham; Hedemann, Mette Skou; Poulsen, Hanne Damgaard

    2016-01-01

    The metabolic response in plasma and urine of pigs when feeding an optimum level of branched chain amino acids (BCAAs) for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAAs intake level that could be linked to ...

  5. A novel branched chain amino acids responsive transcriptional regulator, BCARR, negatively acts on the proteolytic system in Lactobacillus helveticus.

    Directory of Open Access Journals (Sweden)

    Taketo Wakai

    Full Text Available Transcriptional negative regulation of the proteolytic system of Lactobacillus helveticus CM4 in response to amino acids seems to be very important for the control of antihypertensive peptide production; however, it remains poorly understood. A 26-kDa protein with N-terminal cystathionine β-synthase domains (CBS domain protein, which seems to be involved in the regulatory system, was purified by using a DNA-sepharose bound 300-bp DNA fragment corresponding to the upstream regions of the six proteolytic genes that are down-regulated by amino acids. The CBS domain protein bound to a DNA fragment corresponding to the region upstream of the pepV gene in response to branched chain amino acids (BCAAs. The expression of the pepV gene in Escherichia coli grown in BCAA-enriched medium was repressed when the CBS domain protein was co-expressed. These results reveal that the CBS domain protein acts as a novel type of BCAA-responsive transcriptional regulator (BCARR in L. helveticus. From comparative analysis of the promoter regions of the six proteolysis genes, a palindromic AT-rich motif, 5'-AAAAANNCTWTTATT-3', was predicted as the consensus DNA motif for the BCARR protein binding. Footprint analysis using the pepV promotor region and gel shift analyses with the corresponding short DNA fragments strongly suggested that the BCARR protein binds adjacent to the pepV promoter region and affects the transcription level of the pepV gene in the presence of BCAAs. Homology search analysis of the C-terminal region of the BCARR protein suggested the existence of a unique βαββαβ fold structure that has been reported in a variety of ACT (aspartate kinase-chorismate mutase-tyrA domain proteins for sensing amino acids. These results also suggest that the sensing of BCAAs by the ACT domain might promote the binding of the BCARR to DNA sequences upstream of proteolysis genes, which affects the gene expression of the proteolytic system in L. helveticus.

  6. Time-course changes in circulating branched-chain amino acid levels and metabolism in obese Yucatan minipig.

    Science.gov (United States)

    Polakof, Sergio; Rémond, Didier; David, Jérémie; Dardevet, Dominique; Savary-Auzeloux, Isabelle

    2018-06-01

    High-fat high-sucrose diet (HFHS) overfeeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated levels of branched-chain amino acids (BCAAs) have been associated with metabolic dysfunctions, including insulin resistance (IR). The aim of this study was to elucidate whether elevated BCAA levels are the cause or the consequence of IR and to determine the mechanisms and tissues involved in such a phenotype. We performed a 2-mo follow-up on minipigs overfed an HFHS diet and focused on kinetics fasting and postprandial (PP) BCAA levels and BCAA catabolism in key tissues. The study of the fasting BCAA elevation reveals that BCAA accumulation in the plasma compartment is well correlated with IR markers and body weight. Furthermore, the PP excursion of BCAA levels after the last HFHS meal was exacerbated when compared with that of the first meal, suggesting a reduced amino acid oxidation potential. Although only minor changes in BCAA metabolism were observed in liver, muscle, and the visceral adipose tissue, the oxidative deamination potential of the subcutaneous adipose tissue was blunted after 60 d of HFHS feeding. To our knowledge, the present results demonstrated for the first time in a swine model of obesity and IR, the existence of a phenotype related to high-circulating BCAA levels and metabolic dysregulation. The oxidative BCAA capacity reduction specifically in the subcutaneous adipose tissue emerges, at least in the present swine model, as the more plausible metabolic explanation for the elevated blood BCAA phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Associations among circulating branched-chain amino acids and tyrosine with muscle volume and glucose metabolism in individuals without diabetes.

    Science.gov (United States)

    Honda, Tatsuro; Kobayashi, Yoshinao; Togashi, Kenji; Hasegawa, Hiroshi; Iwasa, Motoh; Taguchi, Osamu; Takei, Yoshiyuki; Sumida, Yasuhiro

    2016-05-01

    Amino acid metabolites, including branched-chain amino acids (BCAA) and tyrosine (Tyr), affect glucose metabolism. The effects of BCAA on insulin resistance in patients with diabetes seem to conflict with mechanisms determined in animal models and cultured cells. The aim of this study was to clarify the controversy surrounding the effects of BCAA by investigating the physiological effects of BCAA and Tyr on glucose metabolism in healthy community dwellers. We investigated associations among BCAA and Tyr and metabolic parameters in 78 residents (median age, 52 y) of Mie, Japan, who did not have prediabetes, diabetes, or a body mass index >30 kg/m(2). Muscle volume, serum BCAA, and Tyr levels were higher in men than in women (n = 32 and 46, respectively; all P BCAA positively with muscle volume (regression coefficient/t/p/95% confidence interval, 281.8/3.7/0.0004/129.7-433.8), fasting blood glucose (FBG; 12699.4/3.22/0.0020/4830.9-20567.8), fasting immunoreactive insulin (IRI; 8505.1/2.75/0.0078/2322.5-14687.6), and homeostasis model assessment of β-cell function (HOMA-β; 893.6/2.58/0.0122/201.8-1585.5), and negatively with the HOMA-insulin resistance (HOMA-IR; -9294.1/-2.89/0.0052/-15711.0 to -2877.1). Tyr positively correlated with fasting IRI (26/2.77/0.0072/7.3-44.7). Insulin sensitivity and muscle volume are positively associated with BCAA in individuals without diabetes. In turn, BCAA correlate with increased FBG and fasting IRI levels. Tyr correlated with fasting IRI, but not with insulin sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy.

    Science.gov (United States)

    Zhang, Fuyang; Zhao, Shihao; Yan, Wenjun; Xia, Yunlong; Chen, Xiyao; Wang, Wei; Zhang, Jinglong; Gao, Chao; Peng, Cheng; Yan, Feng; Zhao, Huishou; Lian, Kun; Lee, Yan; Zhang, Ling; Lau, Wayne Bond; Ma, Xinliang; Tao, Ling

    2016-11-01

    The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD+BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD+BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte. Copyright © 2016. Published by Elsevier

  9. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

    Directory of Open Access Journals (Sweden)

    Fuyang Zhang

    2016-11-01

    Full Text Available The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD + BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR, inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA in the HFD + BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.

  10. Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

    Science.gov (United States)

    Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

    2013-01-01

    Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (PBCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

  11. Is administrating branched-chain amino acid-enriched nutrition achieved symptom-free in malnourished cirrhotic patients?

    Science.gov (United States)

    Tsuda, Yasuhiro; Fukui, Hideo; Sujishi, Tetsuya; Ohama, Hideko; Tsuchimoto, Yusuke; Asai, Akira; Fukunisi, Shinya; Higuchi, Kazuhide

    2014-01-01

    Administration of branched-chain amino acids (BCAA) has been reported to improve liver function, quality of life (QOL). However, in some malnourished patients, serum albumin levels do not improve in response to BCAA granules. In this study, we examined the effects of BCAA-enriched enteral nutrition in patients unresponsive to BCAA granules. Thirty-two decompensated cirrhotic patients at Osaka Medical College were enrolled in this study. Since all patients showed no improvement in serum albumin levels despite 3 months of BCAA granule administration, they were administered 50 g of a flavored BCAA-enriched enteral nutrient twice daily, i.e., during the daytime and late evening. Serum albumin levels and major cirrhotic symptoms were examined 1, 3, and 5 months after treatment initiation. Serum albumin levels improved significantly 3 months after treatment initiation (3.14 ± 0.32 g/dl vs 3.5 ± 0.31 g/dl, pBCAA-enriched nutrients improves QOL of cirrhotic patients unresponsive to BCAA granules.

  12. Branched-chain amino acid-enriched nutrient increases blood platelet count in patients after endoscopic injection sclerotherapy.

    Science.gov (United States)

    Furuichi, Yoshihiro; Imai, Yasuharu; Miyata, Yuki; Sugimoto, Katsutoshi; Sano, Takatomo; Taira, Junichi; Kojima, Mayumi; Kobayashi, Yoshiyuki; Nakamura, Ikuo; Moriyasu, Fuminori

    2016-10-01

    Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched-chain amino acid (BCAA)-enriched nutrient are prospectively investigated. A total of 61 LC patients were randomly divided into an EIS monotherapy group (non-BCAA group, n = 31) and an EIS combined with BCAA therapy group (n = 30). Platelet count, blood chemistry and somatometry values were prospectively measured at five time points. The platelet counts before treatment were at the same level in both groups (P = 0.72). Three months after treatment, the counts decreased in the non-BCAA group; however, they increased in the BCAA group (P = 0.019). Body mass index, triceps skin fold thickness and arm muscle circumference significantly decreased in both groups. The BCAA and tyrosine ratio value increased only in the BCAA group (P BCAA group (P BCAA. Administration of BCAA had some effect in maintaining the nutritional state, and may improve the platelet count. Taking a greater amount of nutrients and shorter dietary restriction period or hospitalization was desirable. © 2016 The Japan Society of Hepatology.

  13. Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

    Science.gov (United States)

    Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

    2014-04-01

    Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

  14. High Glucose-Induced Cardiomyocyte Death May Be Linked to Unbalanced Branched-Chain Amino Acids and Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    2018-04-01

    Full Text Available High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by 1H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo. However, we also identified a series of common metabolic changes, including increases in branched-chain amino acids (BCAAs: leucine, isoleucine and valine as well as decreases in aspartate and creatine under high glucose condition. Moreover, a reduced energy metabolism could also be a common metabolic characteristic, as indicated by decreases in ATP in vitro as well as AMP, fumarate and succinate in vivo. Therefore, this study reveals that a decrease in energy metabolism and an increase in BCAAs metabolism could be implicated in high glucose-induced cardiomyocyte death.

  15. NUTRITIONAL INTERACTIONS BETWEEN ZINC AND BRANCHED CHAIN AMINO ACID (BCAA SUPPLEMENT IN RATS: A MULTICOMPARTMENT MODELING APPROACH

    Directory of Open Access Journals (Sweden)

    JAIR RODRIGUES GARCIA-JÊNIOR

    2009-07-01

    Full Text Available

    The influence of supplementary-branched chain amino acids (BCAA on 65Zn metabolism in rats was investigated in this study. Nutritional indicators of Zn, as absorption, body retention and secretion, were estimated using a multicompartment model. Two groups of eight male rats were force-fed a zinc-adequate diet (control group and a zinc-adequate diet plus 0.52 9 BCAA/kg diet during 15 days. There was no significant difference for intake of Zn, absorption (34%, intestinal transit (tso and the leveI of Zn in the intravascular compartment (plasma. On the other hand the extravascular compartment (organs and specific concentration of Zn per 9 of tissue decreased after experimental period (p < 0.05 The rats supplememted with BCAA secreted Zn by urine twice faster than controls, but the secrotion of zinc by endogen feces were not decreased in this group. Thus, BCAA supplement changed the kinetic of Zn, increasing the urinary secretion and the loss of Zn from the body.

  16. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Motoh Iwasa

    Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

  17. The Supplementation of Branched-Chain Amino Acids, Arginine, and Citrulline Improves Endurance Exercise Performance in Two Consecutive Days

    Directory of Open Access Journals (Sweden)

    I-Shiung Cheng, Yi-Wen Wang, I-Fan Chen, Gi-Sheng Hsu, Chun-Fang Hsueh, Chen-Kang Chang

    2016-09-01

    Full Text Available The central nervous system plays a crucial role in fatigue during endurance exercise. Branched-chain amino acids (BCAA could reduce cerebral serotonin synthesis by competing with its precursor tryptophan for crossing the blood brain barrier. Arginine and citrulline could prevent excess hyperammonemia accompanied by BCAA supplementation. This study investigated the combination of BCAA, arginine, and citrulline on endurance performance in two consecutive days. Seven male and three female endurance runners ingested 0.17 g·kg-1 BCAA, 0.05 g·kg-1 arginine and 0.05 g·kg-1 citrulline (AA trial or placebo (PL trial in a randomized cross-over design. Each trial contained a 5000 m time trial on the first day, and a 10000 m time trial on the second day. The AA trial had significantly better performance in 5000 m (AA: 1065.7 ± 33.9 s; PL: 1100.5 ± 40.4 s and 10000 m (AA: 2292.0 ± 211.3 s; PL: 2375.6 ± 244.2 s. The two trials reported similar ratings of perceived exertion. After exercise, the AA trial had significantly lower tryptophan/BCAA ratio, similar NH3, and significantly higher urea concentrations. In conclusion, the supplementation could enhance time-trial performance in two consecutive days in endurance runners, possibly through the inhibition of cerebral serotonin synthesis by BCAA and the prevention of excess hyperammonemia by increased urea genesis.

  18. Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma.

    Science.gov (United States)

    Ishikawa, Toru

    2012-05-07

    The prognosis of hepatocellular carcinoma (HCC) depends on tumor extension as well as hepatic function. Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC; the Child-Pugh classification system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease, using serum albumin level to achieve accurate assessment of the status of protein metabolism. However, insufficient attention has been given to the status of amino acid (AA) metabolism in chronic liver disease and HCC. Fischer's ratio is the molar ratio of branched-chain AAs (BCAAs: leucine, valine, isoleucine) to aromatic AAs (phenylalanine, tyrosine) and is important for assessing liver metabolism, hepatic functional reserve and the severity of liver dysfunction. Although this ratio is difficult to determine in clinical situations, BCAAs/tyrosine molar concentration ratio (BTR) has been proposed as a simpler substitute. BTR correlates with various liver function examinations, including markers of hepatic fibrosis, hepatic blood flow and hepatocyte function, and can thus be considered as reflecting the degree of hepatic impairment. This manuscript examines the literature to clarify whether BTR can serve as a prognostic factor for treatment of HCC.

  19. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

    Science.gov (United States)

    Lackey, Denise E.; Lynch, Christopher J.; Olson, Kristine C.; Mostaedi, Rouzbeh; Ali, Mohamed; Smith, William H.; Karpe, Fredrik; Humphreys, Sandy; Bedinger, Daniel H.; Dunn, Tamara N.; Thomas, Anthony P.; Oort, Pieter J.; Kieffer, Dorothy A.; Amin, Rajesh; Bettaieb, Ahmed; Haj, Fawaz G.; Permana, Paska; Anthony, Tracy G.

    2013-01-01

    Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35–50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals. PMID:23512805

  20. Maintenance of plasma branched-chain amino acid concentrations during glucose infusion directs essential amino acids to extra-mammary tissues in lactating dairy cows.

    Science.gov (United States)

    Curtis, Richelle V; Kim, Julie J M; Doelman, John; Cant, John P

    2018-05-01

    of non-branched-chain essential amino acids by BCAA led to a decrease in milk protein yield. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states.

    Science.gov (United States)

    Holecek, Milan; Siman, Pavel; Vodenicarovova, Melita; Kandar, Roman

    2016-01-01

    Many people believe in favourable effects of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), especially leucine, on muscle protein balance and consume BCAAs for many years. We determined the effects of the chronic intake of a BCAA- or leucine-enriched diet on protein and amino acid metabolism in fed and postabsorptive states. Rats were fed a standard diet, a diet with a high content of valine, leucine, and isoleucine (HVLID), or a high content of leucine (HLD) for 2 months. Half of the animals in each group were sacrificed in the fed state on the last day, and the other half were sacrificed after overnight fast. Protein synthesis was assessed using the flooding dose method (L-[3,4,5-(3)H]phenylalanine), proteolysis on the basis of chymotrypsin-like activity (CHTLA) of proteasome and cathepsin B and L activities. Chronic intake of HVLID or HLD enhanced plasma levels of urea, alanine and glutamine. HVLID also increased levels of all three BCAA and branched-chain keto acids (BCKA), HLD increased leucine, ketoisocaproate and alanine aminotransferase and decreased valine, ketovaline, isoleucine, ketoisoleucine, and LDL cholesterol. Tissue weight and protein content were lower in extensor digitorum longus muscles in the HLD group and higher in kidneys in the HVLID and HLD groups. Muscle protein synthesis in postprandial state was higher in the HVLID group, and CHTLA was lower in muscles of the HVLID and HLD groups compared to controls. Overnight starvation enhanced alanine aminotransferase activity in muscles, and decreased protein synthesis in gastrocnemius (in HVLID group) and extensor digitorum longus (in HLD group) muscles more than in controls. Effect of HVLID and HLD on CHTLA in muscles in postabsorptive state was insignificant. The results failed to demonstrate positive effects of the chronic consumption of a BCAA-enriched diet on protein balance in skeletal muscle and indicate rather negative effects from a leucine-enriched diet. The primary

  2. Analysis of the LIV system of Campylobacter jejuni reveals alternative roles for LivJ and LivK in commensalism beyond branched-chain amino acid transport.

    Science.gov (United States)

    Ribardo, Deborah A; Hendrixson, David R

    2011-11-01

    Campylobacter jejuni is a leading cause of diarrheal disease in humans and an intestinal commensal in poultry and other agriculturally important animals. These zoonotic infections result in significant amounts of C. jejuni present in the food supply to contribute to disease in humans. We previously found that a transposon insertion in Cjj81176_1038, encoding a homolog of the Escherichia coli LivJ periplasmic binding protein of the leucine, isoleucine, and valine (LIV) branched-chain amino acid transport system, reduced the commensal colonization capacity of C. jejuni 81-176 in chicks. Cjj81176_1038 is the first gene of a six-gene locus that encodes homologous components of the E. coli LIV system. By analyzing mutants with in-frame deletions of individual genes or pairs of genes, we found that this system constitutes a LIV transport system in C. jejuni responsible for a high level of leucine acquisition and, to a lesser extent, isoleucine and valine acquisition. Despite each LIV protein being required for branched-chain amino acid transport, only the LivJ and LivK periplasmic binding proteins were required for wild-type levels of commensal colonization of chicks. All LIV permease and ATPase components were dispensable for in vivo growth. These results suggest that the biological functions of LivJ and LivK for colonization are more complex than previously hypothesized and extend beyond a role for binding and acquiring branched-chain amino acids during commensalism. In contrast to other studies indicating a requirement and utilization of other specific amino acids for colonization, acquisition of branched-chain amino acids does not appear to be a determinant for C. jejuni during commensalism.

  3. Branched Chain Amino Acid Suppresses Hepatocellular Cancer Stem Cells through the Activation of Mammalian Target of Rapamycin

    Science.gov (United States)

    Nishitani, Shinobu; Horie, Mayumi; Ishizaki, Sonoko; Yano, Hirohisa

    2013-01-01

    Differentiation of cancer stem cells (CSCs) into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb). mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy. PMID:24312415

  4. Effects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: A randomized trial.

    Science.gov (United States)

    Nojiri, Shunsuke; Fujiwara, Kei; Shinkai, Noboru; Iio, Etsuko; Joh, Takashi

    2017-01-01

    Maintenance of liver function is important for better outcomes after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study was to examine the effects of oral branched-chain amino acid (BCAA) supplementation on liver function, intrahepatic recurrence rate, and incidence of complications after RFA for HCC. Patients with cirrhosis who underwent RFA were enrolled between August 2009 and April 2012, randomized to oral supplementation with Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and health status. Patients in the BCAA group were instructed to ingest a packet of Aminoleban EN twice daily. Levels of physical and mental stress were assessed using the Short Form-8 health survey. Oral BCAA and dietary interventions were initiated 2 wk before local therapy, and contrast-enhanced computed tomography was performed every 3 mo to assess recurrence. We evaluated 25 patients in the BCAA group and 26 in the control group. The median follow-up period was 3.9 y (736-1818 d). There were no significant differences between the two groups in basal characteristics. Complications were less frequent in the BCAA group (P = 0.03). Event-free survival was significantly higher in the BCAA group, whereas the intrahepatic recurrence rate was significantly lower (P = 0.04 and 0.036, respectively). A significant improvement in the Short Form-8 mental component score was observed in the BCAA group only (P < 0.01). Aminoleban EN may be beneficial for cirrhotic patients after RFA to relieve mental stress and reduce the risks for intrahepatic recurrence and complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice

    Science.gov (United States)

    Korenaga, Masaaki; Nishina, Sohji; Korenaga, Keiko; Tomiyama, Yasuyuki; Yoshioka, Naoko; Hara, Yuichi; Sasaki, Yusuke; Shimonaka, Yasushi; Hino, Keisuke

    2015-01-01

    Background & Aims Branched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis. Methods Male HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months. Results For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels. Conclusions BCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients. PMID:25156780

  6. Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women's Health Initiative.

    Science.gov (United States)

    Isanejad, Masoud; LaCroix, Andrea Z; Thomson, Cynthia A; Tinker, Lesley; Larson, Joseph C; Qi, Qibin; Qi, Lihong; Cooper-DeHoff, Rhonda M; Phillips, Lawrence S; Prentice, Ross L; Beasley, Jeannette M

    2017-06-01

    Knowledge regarding association of dietary branched-chain amino acid (BCAA) and type 2 diabetes (T2D), and the contribution of BCAA from meat to the risk of T2D are scarce. We evaluated associations between dietary BCAA intake, meat intake, interaction between BCAA and meat intake and risk of T2D. Data analyses were performed for 74 155 participants aged 50-79 years at baseline from the Women's Health Initiative for up to 15 years of follow-up. We excluded from analysis participants with treated T2D, and factors potentially associated with T2D or missing covariate data. The BCAA and total meat intake was estimated from FFQ. Using Cox proportional hazards models, we assessed the relationship between BCAA intake, meat intake, and T2D, adjusting for confounders. A 20 % increment in total BCAA intake (g/d and %energy) was associated with a 7 % higher risk for T2D (hazard ratio (HR) 1·07; 95 % CI 1·05, 1·09). For total meat intake, a 20 % increment was associated with a 4 % higher risk of T2D (HR 1·04; 95 % CI 1·03, 1·05). The associations between BCAA intake and T2D were attenuated but remained significant after adjustment for total meat intake. These relations did not materially differ with or without adjustment for BMI. Our results suggest that dietary BCAA and meat intake are positively associated with T2D among postmenopausal women. The association of BCAA and diabetes risk was attenuated but remained positive after adjustment for meat intake suggesting that BCAA intake in part but not in full is contributing to the association of meat with T2D risk.

  7. Effects of carbohydrate, branched-chain amino acids, and arginine in recovery period on the subsequent performance in wrestlers

    Directory of Open Access Journals (Sweden)

    Jang Tsong-Rong

    2011-11-01

    Full Text Available Abstract Many athletes need to participate in multiple events in a single day. The efficient post-exercise glycogen recovery may be critical for the performance in subsequent exercise. This study examined whether post-exercise carbohydrate supplementation could restore the performance in the subsequent simulated wrestling match. The effect of branched-chain amino acids and arginine on glucose disposal and performance was also investigated. Nine well-trained male wrestlers participated in 3 trials in a random order. Each trial contained 3 matches with a 1-hr rest between match 1 and 2, and a 2-hr rest between match 2 and 3. Each match contained 3 exercise periods interspersed with 1-min rests. The subjects alternated 10-s all-out sprints and 20-s rests in each exercise period. At the end of match 2, 3 different supplementations were consumed: 1.2 g/kg glucose (CHO trial, 1 g/kg glucose + 0.1 g/kg Arg + 0.1 g/kg BCAA (CHO+AA trial, or water (placebo trial. The peak and average power in the 3 matches was similar in the 3 trials. After the supplementation, CHO and CHO+AA trial showed significantly higher glucose and insulin, and lower glycerol and non-esterified fatty acid concentrations than the placebo trial. There was no significant difference in these biochemical parameters between the CHO and CHO+AA trials. Supplementation of carbohydrate with or without BCAA and arginine during the post-match period had no effect on the performance in the following simulated match in wrestlers. In addition, BCAA and arginine did not provide additional insulinemic effect.

  8. Branched chain amino acid suppresses hepatocellular cancer stem cells through the activation of mammalian target of rapamycin.

    Directory of Open Access Journals (Sweden)

    Shinobu Nishitani

    Full Text Available Differentiation of cancer stem cells (CSCs into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR leads to CSC survival, the effect of branched chain amino acids (BCAAs, an mTOR complex 1 (mTORC1 activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb. mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2 or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy.

  9. Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

    Directory of Open Access Journals (Sweden)

    Urho M Kujala

    2016-11-01

    Full Text Available Aims/hypothesis Existing studies suggest that decreased branched-chain amino acid (BCAA catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid (TCA cycle, intramyocellular lipid storage and oxidation thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. Methods Older Finnish men enriched with individuals having been athletes in young adulthood (n=593; mean age 72.6 ± 5.9 years responded to questionnaires, participated in a clinical examination including assessment of body composition with bioimpedance and gave fasting blood samples for various analytes as well as participated in a 2 hour 75 g oral glucose tolerance test. Metabolomics measurements from serum included BCAAs (isoleucine, leucine and valine.Results Out of the 593 participants 59 had previously known type 2 diabetes, further 67 had screen-detected type 2 diabetes, 127 IGT and 125 IFG while 214 had normal glucose regulation. There were group differences in all of the BCAA concentrations (p≤0.005 for all BCAAs, such that those with normal glucose tolerance had the lowest and those with diabetes mellitus had the highest BCAA concentrations. All BCAA levels correlated positively with body fat percentage (r=.29 - .34, p<.0001 for all. Expected associations with high BCAA concentrations and unfavorable metabolic profile indicators from metabolomics analysis were found. Except for glucose concentrations, the associations were stronger with isoleucine and leucine than with valine. Conclusions/interpretation The findings provided further support for our hypothesis by strengthening the idea that the efficiency of BCAA catabolism

  10. Changes in body composition in heart failure patients after a resistance exercise program and branched chain amino acid supplementation.

    Science.gov (United States)

    Pineda-Juárez, Juan Antonio; Sánchez-Ortiz, Néstor Alonso; Castillo-Martínez, Lilia; Orea-Tejeda, Arturo; Cervantes-Gaytán, Rocío; Keirns-Davis, Candace; Pérez-Ocampo, Carlos; Quiroz-Bautista, Karla; Tenorio-Dupont, Mónica; Ronquillo-Martínez, Alberto

    2016-02-01

    Heart Failure (HF) is a complex syndrome, which can include the physiological, neural hormonal and metabolic complications known as "Cardiac Cachexia" (CC). In the development of CC there is a release of catabolic cytokines (Tumor Necrosis Factor-α, interleukins 1 and 6) that cause a decrease of fat free mass and fat mass. These changes in body composition might be reversed with a therapeutic combination of resistance exercise and branched chain amino acid supplementation (BCAA). Evaluate changes in body composition after a resistance exercise program and BCAA supplementation in patients with HF. In a randomized clinical trial with 3 month of follow-up anthropometric body composition analysis and stress tests were evaluated at the beginning and in the end of the study. Patients were divided into two groups; the experimental group performed the resistance exercise program and received 10 g/day BCAA supplementation, and the control group only performed the resistance exercise program. Both groups were provided with individualized diets and conventional medical treatment. Changes were found in hip circumference between the groups (p = 0.02), and muscle strength was increased in the experimental group (8%) and the control group (11.4%) with no difference between them. METS and VO2Max also increased in experimental and control groups (16.6% and 50.1% respectively). Regarding changes in symptoms, improvements in fatigue (45.4%), decubitus intolerance (21.8%) and dyspnea (25.4%) were observed in the overall sample. Improvements in physical and functional capacities are attributed to resistance exercise program but not to the BCAA supplementation. NCT02240511. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  11. Supplemental branched-chain amino acids improve performance and immune response of newly-received feedlot calves

    Science.gov (United States)

    Supplemental branched-chain AA (BCAA) improved N balance of steers during a simulated pathogen challenge. The objective of this study was to determine the effect of supplemental BCAA on growth and health of newly-received feedlot steers. Steers (n = 120; initial BW = 376 ± 5 kg) were blocked by BW a...

  12. Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors.

    Directory of Open Access Journals (Sweden)

    Ruiyue Yang

    Full Text Available BACKGROUND: Recent studies have determined that branched-chain (BCAAs and aromatic (AAAs amino acids are strongly correlated with obesity and atherogenic dyslipidemia and are strong predictors of diabetes. However, it is not clear if these amino acids are capable of identifying subjects with coronary artery disease (CAD, particularly with subclinical atherosclerosis who are at risk of developing CAD. METHODS: Four hundred and seventy two Chinese subjects (272 males and 200 females, 42-97 y of age undergoing physical exams were recruited at random for participation in the cross-sectional study. Serum BCAAs and AAAs were measured using our previously reported isotope dilution liquid chromatography tandem mass spectrometry method. Bilateral B-mode carotid artery images for carotid intima-media thickness (cIMT were acquired at end diastole and cIMT values more than 0.9 mm were categorized as increased. Correlations of BCAAs with cIMT and other CAD risk factors were analyzed. RESULTS: BCAAs and AAAs were significantly and positively associated with risk factors of CAD, e.g., cIMT, BMI, waist circumference, blood pressure, fasting blood glucose, TG, apoB, apoB/apoAI ratio, apoCII, apoCIII and hsCRP, and were significantly and negatively associated with HDL-C and apoAI. Stepwise multiple linear regression analysis revealed that age (β = 0.175, P<0.001, log BCAA (β = 0.147, P<0.001 and systolic blood pressure (β = 0.141, P = 0.012 were positively and independently associated with cIMT. In the logistic regression model, the most and only powerful laboratory factor correlated with increased cIMT was BCAA (the odds ratio of the fourth quartile compared to the first quartile was 2.679; P = 0.009. CONCLUSION: BCAAs are independently correlated with increased cIMT. This correlation would open a new field of research in the mechanistic understanding and risk assessment of CAD.

  13. Is Branched-Chain Amino Acids Supplementation an Efficient Nutritional Strategy to Alleviate Skeletal Muscle Damage? A Systematic Review

    Directory of Open Access Journals (Sweden)

    Alexandre Fouré

    2017-09-01

    Full Text Available Amino acids and more precisely, branched-chain amino acids (BCAAs, are usually consumed as nutritional supplements by many athletes and people involved in regular and moderate physical activities regardless of their practice level. BCAAs have been initially shown to increase muscle mass and have also been implicated in the limitation of structural and metabolic alterations associated with exercise damage. This systematic review provides a comprehensive analysis of the literature regarding the beneficial effects of BCAAs supplementation within the context of exercise-induced muscle damage or muscle injury. The potential benefit of a BCAAs supplementation was also analyzed according to the supplementation strategy—amount of BCAAs, frequency and duration of the supplementation—and the extent of muscle damage. The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42017073006 and followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Literature search was performed from the date of commencement until August 2017 using four online databases (Medline, Cochrane library, Web of science and ScienceDirect. Original research articles: (i written in English; (ii describing experiments performed in Humans who received at least one oral BCAAs supplementation composed of leucine, isoleucine and valine mixture only as a nutritional strategy and (iii reporting a follow-up of at least one day after exercise-induced muscle damage, were included in the systematic review analysis. Quality assessment was undertaken independently using the Quality Criteria Checklist for Primary Research. Changes in indirect markers of muscle damage were considered as primary outcome measures. Secondary outcome measures were the extent of change in indirect markers of muscle damage. In total, 11 studies were included in the analysis. A high heterogeneity was found regarding the

  14. Genetic predisposition to an impaired metabolism of the branched chain amino acids and risk of type 2 diabetes: A Mendelian randomisation analysis

    OpenAIRE

    Lotta, LA; Scott, RA; Sharp, SJ; Burgess, S; Luan, J; Tillin, T; Schmidt, AF; Imamura, F; Stewart, ID; Perry, JRB; Marney, L; Koulman, A; Karoly, ED; Forouhi, NG; Sjögren, RJO

    2016-01-01

    $\\textbf{BACKGROUND}$: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. $\\textbf{METHODS AND FINDINGS}$: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < ...

  15. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export

    OpenAIRE

    White, Phillip J.; Lapworth, Amanda L.; An, Jie; Wang, Liping; McGarrah, Robert W.; Stevens, Robert D.; Ilkayeva, Olga; George, Tabitha; Muehlbauer, Michael J.; Bain, James R.; Trimmer, Jeff K.; Brosnan, M. Julia; Rolph, Timothy P.; Newgard, Christopher B.

    2016-01-01

    Objective: A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. Methods: Zucker-lean rats (ZLR) and Zucker-fatty rats (Z...

  16. Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: A twin study ?

    OpenAIRE

    Jennings, Amy; MacGregor, Alex; Pallister, Tess; Spector, Tim; Cassidy, Aed?n

    2016-01-01

    Background: Conflicting data exist on the impact of dietary and circulating levels of branched chain amino acids (BCAA) on cardiometabolic health and it is unclear to what extent these relations are mediated by genetics. Methods: In a cross-sectional study of 1997 female twins we examined associations between BCAA intake, measured using food frequency-questionnaires, and a range of markers of cardiometabolic health, including DXA-measured body fat, blood pressure, HOMA-IR, highsensitivity C-r...

  17. The effects of high-fat diet, branched-chain amino acids and exercise on female C57BL/6 mouse Achilles tendon biomechanical properties

    OpenAIRE

    Boivin, G. P.; Platt, K. M.; Corbett, J.; Reeves, J.; Hardy, A. L.; Elenes, E. Y.; Charnigo, R. J.; Hunter, S. A.; Pearson, K. J.

    2013-01-01

    Objectives The goals of this study were: 1) to determine if high-fat diet (HFD) feeding in female mice would negatively impact biomechanical and histologic consequences on the Achilles tendon and quadriceps muscle; and 2) to investigate whether exercise and branched-chain amino acid (BCAA) supplementation would affect these parameters or attenuate any negative consequences resulting from HFD consumption. Methods We examined the effects of 16 weeks of 60% HFD feeding, voluntary exercise (free ...

  18. Abscisic acid-regulated protein degradation causes osmotic stress-induced accumulation of branched-chain amino acids in Arabidopsis thaliana.

    Science.gov (United States)

    Huang, Tengfang; Jander, Georg

    2017-10-01

    Whereas proline accumulates through de novo biosynthesis in plants subjected to osmotic stress, leucine, isoleucine, and valine accumulation in drought-stressed Arabidopsis thaliana is caused by abscisic acid-regulated protein degradation. In response to several kinds of abiotic stress, plants greatly increase their accumulation of free amino acids. Although stress-induced proline increases have been studied the most extensively, the fold-increase of other amino acids, in particular branched-chain amino acids (BCAAs; leucine, isoleucine, and valine), is often higher than that of proline. In Arabidopsis thaliana (Arabidopsis), BCAAs accumulate in response to drought, salt, mannitol, polyethylene glycol, herbicide treatment, and nitrogen starvation. Plants that are deficient in abscisic acid signaling accumulate lower amounts of BCAAs, but not proline and most other amino acids. Previous bioinformatic studies had suggested that amino acid synthesis, rather than protein degradation, is responsible for the observed BCAA increase in osmotically stressed Arabidopsis. However, whereas treatment with the protease inhibitor MG132 decreased drought-induced BCAA accumulation, inhibition of BCAA biosynthesis with the acetolactate synthase inhibitors chlorsulfuron and imazapyr did not. Additionally, overexpression of BRANCHED-CHAIN AMINO ACID TRANSFERASE2 (BCAT2), which is upregulated in response to osmotic stress and functions in BCAA degradation, decreased drought-induced BCAA accumulation. Together, these results demonstrate that BCAA accumulation in osmotically stressed Arabidopsis is primarily the result of protein degradation. After relief of the osmotic stress, BCAA homeostasis is restored over time by amino acid degradation involving BCAT2. Thus, drought-induced BCAA accumulation is different from that of proline, which is accumulated due to de novo synthesis in an abscisic acid-independent manner and remains elevated for a more prolonged period of time after removal of

  19. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    OpenAIRE

    Lotta, L. A.; Scott, R. A.; Sharp, S. J.; Burgess, S.; Luan, J.; Tillin, T.; Schmidt, A. F.; Imamura, F.; Stewart, I. D.; Perry, J. R.; Marney, L.; Koulman, A.; Karoly, E. D.; Forouhi, N. G.; Sjögren, R. J.

    2016-01-01

    BACKGROUND: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. METHODS AND FINDINGS: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8). The strongest si...

  20. The Effects of Adding Whey Protein and Branched-chain Amino Acid to Carbohydrate Beverages on Indices of Muscle Damage after Eccentric Resistance Exercise in Untrained Young Males

    OpenAIRE

    Foad Asjodi; Hamid Mohebi; Ebrahim Mirzajani; Azimeh Izadi

    2017-01-01

    Abstract Background: The aim of this study was to evaluate the effects of supplementation of Branched-Chain Amino Acids (BCAAs) plus carbohydrate (CHO) and whey protein plus CHO on muscle damage indices after eccentric resistant exercise. Materials and Methods: Twenty four untrained healthy males participated in this study. They were randomly divided into three groups, BCAA +glucose (0.1+0.1g/kg) supplement group (n=8), Whey+glucose (0.1+0.1g/kg) supplement group (n=8), and placebo (ma...

  1. Arabidopsis and Maize RidA Proteins Preempt Reactive Enamine/Imine Damage to Branched-Chain Amino Acid Biosynthesis in Plastids[C][W][OPEN

    Science.gov (United States)

    Niehaus, Thomas D.; Nguyen, Thuy N.D.; Gidda, Satinder K.; ElBadawi-Sidhu, Mona; Lambrecht, Jennifer A.; McCarty, Donald R.; Downs, Diana M.; Cooper, Arthur J.L.; Fiehn, Oliver; Mullen, Robert T.; Hanson, Andrew D.

    2014-01-01

    RidA (for Reactive Intermediate Deaminase A) proteins are ubiquitous, yet their function in eukaryotes is unclear. It is known that deleting Salmonella enterica ridA causes Ser sensitivity and that S. enterica RidA and its homologs from other organisms hydrolyze the enamine/imine intermediates that Thr dehydratase forms from Ser or Thr. In S. enterica, the Ser-derived enamine/imine inactivates a branched-chain aminotransferase; RidA prevents this damage. Arabidopsis thaliana and maize (Zea mays) have a RidA homolog that is predicted to be plastidial. Expression of either homolog complemented the Ser sensitivity of the S. enterica ridA mutant. The purified proteins hydrolyzed the enamines/imines formed by Thr dehydratase from Ser or Thr and protected the Arabidopsis plastidial branched-chain aminotransferase BCAT3 from inactivation by the Ser-derived enamine/imine. In vitro chloroplast import assays and in vivo localization of green fluorescent protein fusions showed that Arabidopsis RidA and Thr dehydratase are chloroplast targeted. Disrupting Arabidopsis RidA reduced root growth and raised the root and shoot levels of the branched-chain amino acid biosynthesis intermediate 2-oxobutanoate; Ser treatment exacerbated these effects in roots. Supplying Ile reversed the root growth defect. These results indicate that plastidial RidA proteins can preempt damage to BCAT3 and Ile biosynthesis by hydrolyzing the Ser-derived enamine/imine product of Thr dehydratase. PMID:25070638

  2. Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

    Science.gov (United States)

    Xu, Minjun; Kitaura, Yasuyuki; Ishikawa, Takuya; Kadota, Yoshihiro; Terai, Chihaya; Shindo, Daichi; Morioka, Takashi; Ota, Miki; Morishita, Yukako; Ishihara, Kengo; Shimomura, Yoshiharu

    2017-01-01

    It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

  3. Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

    Directory of Open Access Journals (Sweden)

    Minjun Xu

    Full Text Available It is known that the catabolism of branched-chain amino acids (BCAAs in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK. In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

  4. Rapid and precise measurement of serum branched-chain and aromatic amino acids by isotope dilution liquid chromatography tandem mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Ruiyue Yang

    Full Text Available BACKGROUND: Serum branched-chain and aromatic amino acids (BCAAs and AAAs have emerged as predictors for the future development of diabetes and may aid in diabetes risk assessment. However, the current methods for the analysis of such amino acids in biological samples are time consuming. METHODS: An isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS method for serum BCAAs and AAAs was developed. The serum was mixed with isotope-labeled BCAA and AAA internal standards and the amino acids were extracted with acetonitrile, followed by analysis using LC/MS/MS. The LC separation was performed on a reversed-phase C18 column, and the MS/MS detection was performed via the positive electronic spray ionization in multiple reaction monitoring mode. RESULTS: Specific analysis of the amino acids was achieved within 2 min. Intra-run and total CVs for the amino acids were less than 2% and 4%, respectively, and the analytical recoveries ranged from 99.6 to 103.6%. CONCLUSION: A rapid and precise method for the measurement of serum BCAAs and AAAs was developed and may serve as a quick tool for screening serum BCAAs and AAAs in studies assessing diabetes risk.

  5. Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

    Science.gov (United States)

    Vivar, Juan C.; Knight, Megan S.; Pointer, Mildred A.; Gwathmey, Judith K.; Ghosh, Sujoy

    2014-01-01

    The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of

  6. Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes.

    Directory of Open Access Journals (Sweden)

    Abderrazak Kitsy

    Full Text Available The essential branched-chain amino acids (BCAA, leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2 and branched-chain alpha keto acid dehydrogenase (Bckdha was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4 compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our

  7. Interventions Targeting Glucocorticoid-Krüppel-like Factor 15-Branched-Chain Amino Acid Signaling Improve Disease Phenotypes in Spinal Muscular Atrophy Mice

    Directory of Open Access Journals (Sweden)

    Lisa M. Walter

    2018-05-01

    Full Text Available The circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid (GC-KLF15-BCAA signaling pathway is a key regulatory axis in muscle, whose imbalance has wide-reaching effects on metabolic homeostasis. Spinal muscular atrophy (SMA is a neuromuscular disorder also characterized by intrinsic muscle pathologies, metabolic abnormalities and disrupted sleep patterns, which can influence or be influenced by circadian regulatory networks that control behavioral and metabolic rhythms. We therefore set out to investigate the contribution of the GC-KLF15-BCAA pathway in SMA pathophysiology of Taiwanese Smn−/−;SMN2 and Smn2B/− mouse models. We thus uncover substantial dysregulation of GC-KLF15-BCAA diurnal rhythmicity in serum, skeletal muscle and metabolic tissues of SMA mice. Importantly, modulating the components of the GC-KLF15-BCAA pathway via pharmacological (prednisolone, genetic (muscle-specific Klf15 overexpression and dietary (BCAA supplementation interventions significantly improves disease phenotypes in SMA mice. Our study highlights the GC-KLF15-BCAA pathway as a contributor to SMA pathogenesis and provides several treatment avenues to alleviate peripheral manifestations of the disease. The therapeutic potential of targeting metabolic perturbations by diet and commercially available drugs could have a broader implementation across other neuromuscular and metabolic disorders characterized by altered GC-KLF15-BCAA signaling. Keywords: Spinal muscular atrophy, KLF15, Glucocorticoids, Branched-chain amino acids, Metabolism, Therapy

  8. Comparative metabolism of branched-chain amino acids to precursors of juvenile hormone biogenesis in corpora allata of lepidopterous versus nonlepidopterous insects

    International Nuclear Information System (INIS)

    Brindle, P.A.; Schooley, D.A.; Tsai, L.W.; Baker, F.C.

    1988-01-01

    Comparative studies were performed on the role of branched-chain amino acids (BCAA) in juvenile hormone (JH) biosynthesis using several lepidopterous and nonlepidopterous insects. Corpora cardiaca-corpora allata complexes (CC-CA, the corpora allata being the organ of JH biogenesis) were maintained in culture medium containing a uniformly 14 C-labeled BCAA, together with [methyl- 3 H]methionine as mass marker for JH quantification. BCAA catabolism was quantified by directly analyzing the medium for the presence of 14 C-labeled propionate and/or acetate, while JHs were extracted, purified by liquid chromatography, and subjected to double-label liquid scintillation counting. Our results indicate that active BCAA catabolism occurs within the CC-CA of lepidopterans, and this efficiently provides propionyl-CoA (from isoleucine or valine) for the biosynthesis of the ethyl branches of JH I and II. Acetyl-CoA, formed from isoleucine or leucine catabolism, is also utilized by lepidopteran CC-CA for biosynthesizing JH III and the acetate-derived portions of the ethyl-branched JHs. In contrast, CC-CA of nonlepidopterans fail to catabolize BCAA. Consequently, exogenous isoleucine or leucine does not serve as a carbon source for the biosynthesis of JH III by these glands, and no propionyl-CoA is produced for genesis of ethyl-branched JHs. This is the first observation of a tissue-specific metabolic difference which in part explains why these novel homosesquiterpenoids exist in lepidopterans, but not in nonlepidopterans

  9. Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

    Science.gov (United States)

    Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

    2016-10-01

    Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

  10. A 48-Hour Vegan Diet Challenge in Healthy Women and Men Induces a BRANCH-Chain Amino Acid Related, Health Associated, Metabolic Signature.

    Science.gov (United States)

    Draper, Colleen Fogarty; Vassallo, Irene; Di Cara, Alessandro; Milone, Cristiana; Comminetti, Ornella; Monnard, Irina; Godin, Jean-Philippe; Scherer, Max; Su, MingMing; Jia, Wei; Guiraud, Seu-Ping; Praplan, Fabienne; Guignard, Laurence; Ammon Zufferey, Corinne; Shevlyakova, Maya; Emami, Nashmil; Moco, Sofia; Beaumont, Maurice; Kaput, Jim; Martin, Francois-Pierre

    2018-02-01

    Research is limited on diet challenges to improve health. A short-term, vegan protein diet regimen nutritionally balanced in macronutrient composition compared to an omnivorous diet is hypothesized to improve metabolic measurements of blood sugar regulation, blood lipids, and amino acid metabolism. This randomized, cross-over, controlled vegan versus animal diet challenge is conducted on 21 (11 female,10 male) healthy participants. Fasting plasma is measured during a 3 d diet intervention for clinical biochemistry and metabonomics. Intervention diet plans meet individual caloric needs. Meals are provided and supervised. Diet compliance is monitored. The vegan diet lowers triglycerides, insulin and homeostatic model assessment (HOMA-IR), bile acids, elevated magnesium levels, and changed branched-chain amino acids (BCAAs) metabolism (p vegan versus omnivorous diets. Plasma amino acid and magnesium concentrations positively correlate with dietary amino acids. Polyunsaturated fatty acids and dietary fiber inversely correlate with insulin, HOMA-IR, and triglycerides. Nutritional biochemistries, BCAAs, insulin, and HOMA-IR are impacted by sexual dimorphism. A health-promoting, BCAA-associated metabolic signature is produced from a short-term, healthy, controlled, vegan diet challenge when compared with a healthy, controlled, omnivorous diet. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

    Science.gov (United States)

    Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

    2013-09-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.

  12. Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study.

    Science.gov (United States)

    Lee, Ik Jae; Seong, Jinsil; Bae, Jung Im; You, Sei Hwan; Rhee, Yumie; Lee, Jong Ho

    2011-03-01

    The present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy. Patients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored. Fifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043). Oral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.

  13. Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle.

    Science.gov (United States)

    Borgenvik, Marcus; Apró, William; Blomstrand, Eva

    2012-03-01

    Resistance exercise and amino acids are two major factors that influence muscle protein turnover. Here, we examined the effects of resistance exercise and branched-chain amino acids (BCAA), individually and in combination, on the expression of anabolic and catabolic genes in human skeletal muscle. Seven subjects performed two sessions of unilateral leg press exercise with randomized supplementation with BCAA or flavored water. Biopsies were collected from the vastus lateralis muscle of both the resting and exercising legs before and repeatedly after exercise to determine levels of mRNA, protein phosphorylation, and amino acid concentrations. Intake of BCAA reduced (P exercising legs, respectively. The level of MuRF-1 mRNA was elevated (P exercising leg two- and threefold under the placebo and BCAA conditions, respectively, whereas MuRF-1 total protein increased by 20% (P exercising muscle. In conclusion, BCAA ingestion reduced MAFbx mRNA and prevented the exercise-induced increase in MuRF-1 total protein in both resting and exercising leg. Further-more, resistance exercise differently influenced MAFbx and MuRF-1 mRNA expression, suggesting both common and divergent regulation of these two ubiquitin ligases.

  14. The effect of increased branched-chain amino acid transaminase activity in yeast on the production of higher alcohols and on the flavour profiles of wine and distillates.

    Science.gov (United States)

    Lilly, Mariska; Bauer, Florian F; Styger, Gustav; Lambrechts, Marius G; Pretorius, Isak S

    2006-08-01

    In Saccharomyces cerevisiae, branched-chain amino acid transaminases (BCAATases) are encoded by the BAT1 and BAT2 genes. BCAATases catalyse the transfer of amino groups between those amino acids and alpha-keto-acids. alpha-Keto-acids are precursors for the biosynthesis of higher alcohols, which significantly influence the aroma and flavour of yeast-derived fermentation products. The objective of this study was to investigate the influence of BAT-gene expression on general yeast physiology, on aroma and flavour compound formation and on the sensory characteristics of wines and distillates. For this purpose, the genes were overexpressed and deleted in a laboratory strain, BY4742, and overexpressed in an industrial wine yeast strain, VIN13. The data show that, with the exception of a slow growth phenotype observed for the BAT1 deletion strain, the fermentation behaviour of the strains was unaffected by the modifications. The chemical and sensory analysis of fermentation products revealed a strong correction between BAT gene expression and the formation of many aroma compounds. The data suggest that the adjustment of BAT gene expression could play an important role in assisting winemakers in their endeavour to produce wines with specific flavour profiles.

  15. Targeted metabolomic analysis reveals the association between the postprandial change in palmitic acid, branched-chain amino acids and insulin resistance in young obese subjects.

    Science.gov (United States)

    Liu, Liyan; Feng, Rennan; Guo, Fuchuan; Li, Ying; Jiao, Jundong; Sun, Changhao

    2015-04-01

    Obesity is the result of a positive energy balance and often leads to difficulties in maintaining normal postprandial metabolism. The changes in postprandial metabolites after an oral glucose tolerance test (OGTT) in young obese Chinese men are unclear. In this work, the aim is to investigate the complex metabolic alterations in obesity provoked by an OGTT using targeted metabolomics. We used gas chromatography-mass spectrometry and ultra high performance liquid chromatography-triple quadrupole mass spectrometry to analyze serum fatty acids, amino acids and biogenic amines profiles from 15 control and 15 obese subjects at 0, 30, 60, 90 and 120 min during an OGTT. Metabolite profiles from 30 obese subjects as independent samples were detected in order to validate the change of metabolites. There were the decreased levels of fatty acid, amino acids and biogenic amines after OGTT in obesity. At 120 min, percent change of 20 metabolites in obesity has statistical significance when comparing with the controls. The obese parameters was positively associated with changes in arginine and histidine (Pchange in palmitic acid (PA), branched-chain amino acids (BCAAs) and phenylalanine between 1 and 120 min were positively associated with fasting insulin and HOMA-IR (all Presistance in obesity. Our findings offer new insights in the complex physiological regulation of the metabolism during an OGTT in obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. The Effects of Adding Whey Protein and Branched-chain Amino Acid to Carbohydrate Beverages on Indices of Muscle Damage after Eccentric Resistance Exercise in Untrained Young Males

    Directory of Open Access Journals (Sweden)

    Foad Asjodi

    2017-07-01

    Full Text Available Abstract Background: The aim of this study was to evaluate the effects of supplementation of Branched-Chain Amino Acids (BCAAs plus carbohydrate (CHO and whey protein plus CHO on muscle damage indices after eccentric resistant exercise. Materials and Methods: Twenty four untrained healthy males participated in this study. They were randomly divided into three groups, BCAA +glucose (0.1+0.1g/kg supplement group (n=8, Whey+glucose (0.1+0.1g/kg supplement group (n=8, and placebo (malto dextrin 0.2g/kg group (n=8. Each subject consumed a carbohydrate beverage with addition of whey protein or branched-chain amino acid or placebo 30 minutes before exercise in a randomized,double-blind fashion. Serum levels of Creatine Kinase (CK, Lactate dehydrogenase (LDH, and muscle pain were measured before, 24, 48, 72 h after exercise. Follow-up analyses included 1-way repeated measures ANOVAs, and Bonferroni post hoc comparisons. Results: 24 h after test, serum levels of CK, LDH and muscle pain in both supplement groups were increased less than placebo group (0.015, 0.001 and 0.001, respectively. Also, the levels of CK and LDH showed significant changes in both intervention groups compared to placebo group at 24 h (0.001, 0. 015, respectively. Similarly, significant differences in the levels of CK and LDH between groups were observed. Conclusion: These data indicate that muscle damage and pain after resistant exercise were reduced by an ingestion of either BCAA drink or whey protein drink.

  17. Effects of EPSPS Copy Number Variation (CNV and Glyphosate Application on the Aromatic and Branched Chain Amino Acid Synthesis Pathways in Amaranthus palmeri

    Directory of Open Access Journals (Sweden)

    Manuel Fernández-Escalada

    2017-11-01

    Full Text Available A key enzyme of the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19, is the known target of the widely used herbicide glyphosate. Glyphosate resistance in Amaranthus palmeri, one of the most troublesome weeds in agriculture, has evolved through increased EPSPS gene copy number. The aim of this work was to study the pleiotropic effects of (i EPSPS increased transcript abundance due to gene copy number variation (CNV and of (ii glyphosate application on the aromatic amino acid (AAA and branched chain amino acid (BCAA synthesis pathways. Hydroponically grown glyphosate sensitive (GS and glyphosate resistant (GR plants were treated with glyphosate 3 days after treatment. In absence of glyphosate treatment, high EPSPS gene copy number had only a subtle effect on transcriptional regulation of AAA and BCAA pathway genes. In contrast, glyphosate treatment provoked a general accumulation of the transcripts corresponding to genes of the AAA pathway leading to synthesis of chorismate in both GS and GR. After chorismate, anthranilate synthase transcript abundance was higher while chorismate mutase transcription showed a small decrease in GR and remained stable in GS, suggesting a regulatory branch point in the pathway that favors synthesis toward tryptophan over phenylalanine and tyrosine after glyphosate treatment. This was confirmed by studying enzyme activities in vitro and amino acid analysis. Importantly, this upregulation was glyphosate dose dependent and was observed similarly in both GS and GR populations. Glyphosate treatment also had a slight effect on the expression of BCAA genes but no general effect on the pathway could be observed. Taken together, our observations suggest that the high CNV of EPSPS in A. palmeri GR populations has no major pleiotropic effect on the expression of AAA biosynthetic genes, even in response to glyphosate treatment. This finding supports the idea that the fitness cost associated

  18. Effect of a keto acid-amino acid supplement on the metabolism and renal elimination of branched-chain amino acids in patients with chronic renal insufficiency on a low protein diet.

    Science.gov (United States)

    Teplan, V; Schück, O; Horácková, M; Skibová, J; Holecek, M

    2000-10-27

    The aim of our study was to evaluate the effect of a low-protein diet supplemented with keto acids-amino acids on renal function and urinary excretion of branched-chain amino acids (BCAA) in patients with chronic renal insufficiency (CRI). In a prospective investigation 28 patients with CRI (16 male, 12 female, aged 28-66 yrs, CCr 18.6 +/- 10.2 ml/min) on a low-protein diet (0.6 g of protein /kg BW/day and energy intake 140 kJ/kg BW/day) for a period of one month were included. Subsequently, this low protein diet was supplemented with keto acids-amino acids at a dose of 0.1 g/kg BW/day orally for a period of 3 months. Examinations performed at baseline and at the end of the follow-up period revealed significant increase in the serum levels of BCAA leucine (p Keto acid-amino acid administration had no effect on renal function and on the clearance of inulin, para-aminohippuric acid. Endogenous creatinine and urea clearance remained unaltered. A significant correlation between fractional excretion of sodium and leucine (p diet the supplementation of keto acids-amino acids does not affect renal hemodynamics, but is associated--despite increases in plasma concentrations--with a reduction of renal amino acid and protein excretion suggesting induction of alterations in the tubular transport mechanisms.

  19. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

    Science.gov (United States)

    Lotta, Luca A.; Scott, Robert A.; Luan, Jian’an; Tillin, Therese; Stewart, Isobel D.; Perry, John R. B.; Karoly, Edward D.; Forouhi, Nita G.; Zierath, Juleen R.; Savage, David B.; Griffin, Julian L.; Hingorani, Aroon D.; Khaw, Kay-Tee; O’Rahilly, Stephen; Langenberg, Claudia

    2016-01-01

    Background Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Methods and Findings Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26–1.65, p = 9.5 × 10−8) for isoleucine, 1.85 (95% CI 1.41–2.42, p = 7.3 × 10−6) for leucine, and 1.54 (95% CI 1.28–1.84, p = 4.2 × 10−6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Conclusions Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the

  20. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Directory of Open Access Journals (Sweden)

    Luca A Lotta

    2016-11-01

    Full Text Available Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question.Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8. The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25, encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8 for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6 for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6 for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are

  1. Comparative metabolism of branched-chain amino acids to precursors of juvenile hormone biogenesis in corpora allata of lepidopterous versus nonlepidopterous insects

    Energy Technology Data Exchange (ETDEWEB)

    Brindle, P.A.; Schooley, D.A.; Tsai, L.W.; Baker, F.C.

    1988-08-05

    Comparative studies were performed on the role of branched-chain amino acids (BCAA) in juvenile hormone (JH) biosynthesis using several lepidopterous and nonlepidopterous insects. Corpora cardiaca-corpora allata complexes (CC-CA, the corpora allata being the organ of JH biogenesis) were maintained in culture medium containing a uniformly /sup 14/C-labeled BCAA, together with (methyl-/sup 3/H)methionine as mass marker for JH quantification. BCAA catabolism was quantified by directly analyzing the medium for the presence of /sup 14/C-labeled propionate and/or acetate, while JHs were extracted, purified by liquid chromatography, and subjected to double-label liquid scintillation counting. Our results indicate that active BCAA catabolism occurs within the CC-CA of lepidopterans, and this efficiently provides propionyl-CoA (from isoleucine or valine) for the biosynthesis of the ethyl branches of JH I and II. Acetyl-CoA, formed from isoleucine or leucine catabolism, is also utilized by lepidopteran CC-CA for biosynthesizing JH III and the acetate-derived portions of the ethyl-branched JHs. In contrast, CC-CA of nonlepidopterans fail to catabolize BCAA. Consequently, exogenous isoleucine or leucine does not serve as a carbon source for the biosynthesis of JH III by these glands, and no propionyl-CoA is produced for genesis of ethyl-branched JHs. This is the first observation of a tissue-specific metabolic difference which in part explains why these novel homosesquiterpenoids exist in lepidopterans, but not in nonlepidopterans.

  2. Cloning and inactivation of a branched-chain-amino-acid aminotransferase gene from Staphylococcus carnosus and characterization of the enzyme

    DEFF Research Database (Denmark)

    Madsen, Søren M; Beck, Hans Christian; Ravn, Peter

    2002-01-01

    . The first step in the catabolism is most likely a transamination reaction catalyzed by BCAA aminotransferases (IlvE proteins). In this study, we cloned the ilvE gene from S. carnosus by using degenerate oligonucleotides and PCR. We found that the deduced amino acid sequence was 80% identical...... were essential for optimal cell growth....

  3. Branched-chain Amino Acids are Beneficial to Maintain Growth Performance and Intestinal Immune-related Function in Weaned Piglets Fed Protein Restricted Diet.

    Science.gov (United States)

    Ren, M; Zhang, S H; Zeng, X F; Liu, H; Qiao, S Y

    2015-12-01

    As a novel approach for disease control and prevention, nutritional modulation of the intestinal health has been proved. However, It is still unknown whether branched-chain amino acid (BCAA) is needed to maintain intestinal immune-related function. The objective of this study was to determine whether BCAA supplementation in protein restricted diet affects growth performance, intestinal barrier function and modulates post-weaning gut disorders. One hundred and eight weaned piglets (7.96±0.26 kg) were randomly fed one of the three diets including a control diet (21% crude protein [CP], CON), a protein restricted diet (17% CP, PR) and a BCAA diet (BCAA supplementation in the PR diet) for 14 d. The growth performance, plasma amino acid concentrations, small intestinal morphology and intestinal immunoglobulins were tested. First, average daily gain (ADG) (pBCAA group improved ADG (pBCAA groups was not different (p>0.05). The PR and BCAA treatments had a higher (pBCAA supplementation significantly increased BCAA concentrations (pBCAA supplementation increased villous height in the duodenum (pBCAA supplementation increased levels of jejunal and ileal immunoglobulin mentioned above. In conclusion, BCAA supplementation to protein restricted diet improved intestinal immune defense function by protecting villous morphology and by increasing levels of intestinal immunoglobulins in weaned piglets. Our finding has the important implication that BCAA may be used to reduce the negative effects of a protein restricted diet on growth performance and intestinal immunity in weaned piglets.

  4. High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model

    Science.gov (United States)

    Wessels, Anna G.; Kluge, Holger; Hirche, Frank; Kiowski, Andreas; Schutkowski, Alexandra; Corrent, Etienne; Bartelt, Jörg; König, Bettina; Stangl, Gabriele I.

    2016-01-01

    In addition to its role as an essential protein component, leucine (Leu) displays several other metabolic functions such as activation of protein synthesis. This property makes it an interesting amino acid for the therapy of human muscle atrophy and for livestock production. However, Leu can stimulate its own degradation via the branched-chain keto acid dehydrogenase complex (BCKDH). To examine the response of several tissues to excessive Leu, pigs were fed diets containing two- (L2) and four-fold (L4) higher Leu contents than the recommended amount (control). We found that the L4 diet led to a pronounced increase in BCKDH activity in the brain (2.5-fold, P diet had only weak effects on BCKDH activity. Both high Leu diets reduced the concentrations of free valine and isoleucine in nearly all tissues. In the brain, high Leu diets modified the amount of tryptophan available: for serotonin synthesis. Compared to the controls, pigs treated with the high Leu diets consumed less food, showed increased plasma concentrations of 3-hydroxybutyrate and reduced levels of circulating serotonin. In conclusion, excessive Leu can stimulate BCKDH activity in several tissues, including the brain. Changes in cerebral tryptophan, along with the changes in amino acid-derived metabolites in the plasma may limit the use of high Leu diets to treat muscle atrophy or to increase muscle growth. PMID:26930301

  5. Expression, purification, crystallization and preliminary X-ray analysis of a novel N-substituted branched-chain l-amino-acid dioxygenase from Burkholderia ambifaria AMMD

    International Nuclear Information System (INIS)

    Qin, Hui-Min; Miyakawa, Takuya; Nakamura, Akira; Xue, You-Lin; Kawashima, Takashi; Kasahara, Takuya; Hibi, Makoto; Ogawa, Jun; Tanokura, Masaru

    2012-01-01

    Diffraction data were collected to a limiting resolution of 2.4 Å from a crystal of selenomethionyl-labelled SadA, an l-amino-acid dioxygenase. Ferrous ion- and α-ketoglutarate-dependent dioxygenase from Burkholderia ambifaria AMMD (SadA) catalyzes the C3-hydroxylation of N-substituted branched-chain l-amino acids, especially N-succinyl-l-leucine, coupled to the conversion of α-ketoglutarate to succinate and CO 2 . SadA was expressed in Escherichia coli, purified and crystallized using the sitting-drop vapour-diffusion method at 293 K. Crystals of selenomethionine-substituted SadA were obtained using a reservoir solution containing PEG 3000 as the precipitant at pH 9.5 and diffracted X-rays to 2.4 Å resolution. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 49.3, b = 70.9, c = 148.2 Å. The calculated Matthews coefficient (V M = 2.1 Å 3 Da −1 , 41% solvent content) suggested that the crystal contains two molecules per asymmetric unit

  6. Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.

    Science.gov (United States)

    Kaiser, Julienne C; King, Alyssa N; Grigg, Jason C; Sheldon, Jessica R; Edgell, David R; Murphy, Michael E P; Brinsmade, Shaun R; Heinrichs, David E

    2018-01-01

    Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.

  7. Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.

    Directory of Open Access Journals (Sweden)

    Julienne C Kaiser

    2018-01-01

    Full Text Available Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.

  8. Roux-en-Y Gastric Bypass Surgery, but Not Calorie Restriction, Reduces Plasma Branched-Chain Amino Acids in Obese Women Independent of Weight Loss or the Presence of Type 2 Diabetes

    NARCIS (Netherlands)

    Lips, M.A.; Klinken, J.B. van; Harmelen, V. van; Dharuri, H.K.; Hoen, P.A.C. 't; Laros, J.F.; Ommen, G.J.B. van; Janssen, I.M; Ramshorst, B. van; Wagensveld, B.A. van; Swank, D.J.; Dielen, F. Van; Dane, A.; Harms, A.; Vreeken, R.; Hankemeier, T.; Smit, J.W.A.; Pijl, H.; Dijk, K van

    2014-01-01

    OBJECTIVE: Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA

  9. Whey protein supplementation does not alter plasma branched-chained amino acid profiles but results in unique metabolomics patterns in obese women enrolled in an 8-week weight loss trial

    Science.gov (United States)

    Background: It has been suggested that perturbations in branched-chain amino acid (BCAA) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs. Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism, but there is limited evidence...

  10. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Science.gov (United States)

    Lotta, Luca A; Scott, Robert A; Sharp, Stephen J; Burgess, Stephen; Luan, Jian'an; Tillin, Therese; Schmidt, Amand F; Imamura, Fumiaki; Stewart, Isobel D; Perry, John R B; Marney, Luke; Koulman, Albert; Karoly, Edward D; Forouhi, Nita G; Sjögren, Rasmus J O; Näslund, Erik; Zierath, Juleen R; Krook, Anna; Savage, David B; Griffin, Julian L; Chaturvedi, Nishi; Hingorani, Aroon D; Khaw, Kay-Tee; Barroso, Inês; McCarthy, Mark I; O'Rahilly, Stephen; Wareham, Nicholas J; Langenberg, Claudia

    2016-11-01

    Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.

  11. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.

    Science.gov (United States)

    White, Phillip J; Lapworth, Amanda L; An, Jie; Wang, Liping; McGarrah, Robert W; Stevens, Robert D; Ilkayeva, Olga; George, Tabitha; Muehlbauer, Michael J; Bain, James R; Trimmer, Jeff K; Brosnan, M Julia; Rolph, Timothy P; Newgard, Christopher B

    2016-07-01

    A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES). We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism. LF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH), was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp. Our data are consistent with a model wherein elevated circulating BCAA contribute to development of

  12. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export

    Directory of Open Access Journals (Sweden)

    Phillip J. White

    2016-07-01

    Full Text Available Objective: A branched-chain amino acid (BCAA-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. Methods: Zucker-lean rats (ZLR and Zucker-fatty rats (ZFR were fed either a custom control, low fat (LF diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val were reduced by 45% (LF-RES. We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism. Results: LF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH, was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp. Conclusions: Our data are consistent with a model wherein

  13. Whey protein hydrolysate and branched-chain amino acids downregulate inflammation-related genes in vascular endothelial cells.

    Science.gov (United States)

    Da Silva, Marine S; Bigo, Cyril; Barbier, Olivier; Rudkowska, Iwona

    2017-02-01

    A recent review of clinical studies reports that dairy products may improve inflammation, a key etiologic cardiovascular disease risk factor. Yet the impact of dairy proteins on inflammatory markers is controversial and could be mediated by a differential impact of whey proteins and caseins. In this study, we hypothesized that whey proteins may have a greater anti-inflammatory effect than caseins. A model of human umbilical vein endothelial cells, with or without TNF-α stimulation, was used to investigate the effect of several dairy protein compounds on inflammation. Specifically, the impact of whey proteins either isolate or hydrolysate, caseins, and their amino acids on expression of TNF, VCAM-1, SOD2, and eNOS was examined. After a 24-hour incubation period, whey protein hydrolysate, leucine, isoleucine, and valine attenuated the TNF-α-induced endothelial inflammation by normalizing TNF and eNOS gene expression. This effect was not observed in unstimulated cells. Oppositely, caseins, a whey protein/casein mixture (1:4 w/w), and glutamine aggravated the TNF-α-induced TNF and SOD2 gene expression. Yet caseins and whey protein/casein mixture decreased VCAM-1 expression in both unstimulated and stimulated human umbilical vein endothelial cells. Measurement of TNF-α in cell supernatants by immunoassay substantiates gene expression data without reaching statistical significance. Taken together, this study showed that whey proteins and their major amino acids normalize TNF-α-induced proinflammatory gene expression in endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

    Science.gov (United States)

    Chiarla, C; Siegel, J H; Kidd, S; Coleman, B; Mora, R; Tacchino, R; Placko, R; Gum, M; Wiles, C E; Belzberg, H

    1988-08-01

    Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was

  15. Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life.

    Science.gov (United States)

    Velazquez, Miguel A; Sheth, Bhavwanti; Smith, Stephanie J; Eckert, Judith J; Osmond, Clive; Fleming, Tom P

    2018-02-01

    Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin+N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin+N-bcaa, N-insulin+L-bcaa, and L-insulin+N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: A twin study.

    Science.gov (United States)

    Jennings, Amy; MacGregor, Alex; Pallister, Tess; Spector, Tim; Cassidy, Aedín

    2016-11-15

    Conflicting data exist on the impact of dietary and circulating levels of branched chain amino acids (BCAA) on cardiometabolic health and it is unclear to what extent these relations are mediated by genetics. In a cross-sectional study of 1997 female twins we examined associations between BCAA intake, measured using food frequency-questionnaires, and a range of markers of cardiometabolic health, including DXA-measured body fat, blood pressure, HOMA-IR, high-sensitivity C-reactive protein (hs-CRP) and lipids. We also measured plasma concentrations of BCAA and known metabolites of amino acid metabolism using untargeted mass spectrometry. Using a within-twin design, multivariable analyses were used to compare the associations between BCAA intake and endpoints of cardiometabolic health, independently of genetic confounding. Higher BCAA intake was significantly associated with lower HOMA-IR (-0.1, P-trend 0.02), insulin (-0.5μU/mL, P-trend 0.03), hs-CRP -0.3mg/L, P-trend 0.01), systolic blood pressure (-2.3mmHg, P-trend 0.01) and waist-to-height ratio (-0.01, P-trend 0.04), comparing extreme quintiles of intake. These associations persisted in within-pair analysis for monozygotic twins for insulin resistance (PBCAA intake and plasma concentrations, although two metabolites previously associated with obesity were inversely associated with BCAA intake (alpha-hydroxyisovalerate and trans-4-hydroxyproline). Higher intakes of BCAA were associated, independently of genetics, with lower insulin resistance, inflammation, blood pressure and adiposity-related metabolites. The BCAA intake associated with our findings is easily achievable in the habitual diet. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model.

    Directory of Open Access Journals (Sweden)

    Anna G Wessels

    Full Text Available In addition to its role as an essential protein component, leucine (Leu displays several other metabolic functions such as activation of protein synthesis. This property makes it an interesting amino acid for the therapy of human muscle atrophy and for livestock production. However, Leu can stimulate its own degradation via the branched-chain keto acid dehydrogenase complex (BCKDH. To examine the response of several tissues to excessive Leu, pigs were fed diets containing two- (L2 and four-fold (L4 higher Leu contents than the recommended amount (control. We found that the L4 diet led to a pronounced increase in BCKDH activity in the brain (2.5-fold, P < 0.05, liver (1.8-fold, P < 0.05 and cardiac muscle (1.7-fold, P < 0.05, whereas we found no changes in enzyme activity in the pancreas, skeletal muscle, adipose tissue and intestinal mucosa. The L2 diet had only weak effects on BCKDH activity. Both high Leu diets reduced the concentrations of free valine and isoleucine in nearly all tissues. In the brain, high Leu diets modified the amount of tryptophan available: for serotonin synthesis. Compared to the controls, pigs treated with the high Leu diets consumed less food, showed increased plasma concentrations of 3-hydroxybutyrate and reduced levels of circulating serotonin. In conclusion, excessive Leu can stimulate BCKDH activity in several tissues, including the brain. Changes in cerebral tryptophan, along with the changes in amino acid-derived metabolites in the plasma may limit the use of high Leu diets to treat muscle atrophy or to increase muscle growth.

  18. Wolbachia-induced loss of male fertility is likely related to branch chain amino acid biosynthesis and iLvE in Laodelphax striatellus.

    Science.gov (United States)

    Ju, Jia-Fei; Hoffmann, Ary A; Zhang, Yan-Kai; Duan, Xing-Zhi; Guo, Yan; Gong, Jun-Tao; Zhu, Wen-Chao; Hong, Xiao-Yue

    2017-06-01

    Wolbachia are endosymbionts that infect many species of arthropods and nematodes. Wolbachia-induced cytoplasmic incompatibility (CI) is the most common phenotype in affected hosts, involving embryonic lethality in crosses between Wolbachia-infected males and uninfected females. The molecular mechanisms underlying this phenomenon are currently unclear. Here we examine the molecular correlates of the Wolbachia infection in Laodelphax striatellus (Fallén), an important rice pest, where embryonic lethality is strong and almost complete. We compared the gene expression of 4-day-old Wolbachia-infected and uninfected L. striatellus testes to identify candidate genes for paternal-effect embryonic lethality induction. Based on microarray analysis, iLvE was the most down-regulated gene; this gene mediates branched-chain amino acid (BCAA) biosynthesis and participates in many processes related to reproductive performance. After knocking down iLvE by RNAi in uninfected male L. striatellus, male fertility was reduced, leading to a decrease in embryo hatching rates, but fertility was rescued in crosses between these males and Wolbachia-infected females. Removal of BCAA in chemically-defined diets of uninfected males also led to a loss of male fertility. Low amino acid nutrition may enhance exposure time of sperm to Wolbachia in the testes to affect adult reproduction in L. striatellus by reducing the number of sperm transferred per mating by males. These results indicate that Wolbachia may decrease male fertility in L. striatellus by acting on iLvE, a key factor of BCAA biosynthesis, and delaying sperm maturation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation.

    Science.gov (United States)

    Holeček, Milan

    2017-09-01

    Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles. The article also demonstrates that the favorable effects of BCAA supplementation might be associated with three adverse effects: draining of α-KG from tricarboxylic acid cycle (cataplerosis), increased GLN content and altered glutamatergic neurotransmission in the brain, and activated GLN catabolism to ammonia in the gut and kidneys. Cataplerosis of α-KG can be attenuated by dimethyl-α-ketoglutarate, l-ornithine-l-aspartate, and ornithine salt of α-KG. The pros and cons of GLN elimination from the body using phenylbutyrate (phenylacetate), which may impair liver regeneration and decrease BCAA levels, should be examined. The therapeutic potential of BCAA might be enhanced also by optimizing its supplementation protocol. It is concluded that the search for strategies attenuating adverse and increasing positive effects of the BCAA is needed to include the BCAA among standard medications for patients with cirrhosis of the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. "Weariness" and "unpleasantness" reduce adherence to branched-chain amino acid granules among Japanese patients with liver cirrhosis: results of a single-center cross-sectional survey.

    Science.gov (United States)

    Eguchi, Yuichiro; Furukawa, Naoko; Furukawa, Takeshi; Egashira, Yoshimitsu; Hotokezaka, Hiroshi; Oeda, Satoshi; Iwane, Shinji; Anzai, Keizo

    2017-03-01

    Branched-chain amino acids (BCAA) are valuable in the treatment of liver cirrhosis because they increase serum albumin levels. Poor adherence to BCAA may adversely affect prognosis, but little is known about factors predicting adherence. We undertook a survey of patients prescribed BCAA for the treatment of cirrhosis. Pharmacists carried out face-to-face interviews with patients (or their representatives) prescribed any of nine BCAA formulations. Question categories included patient characteristics, prescription of BCAA granules, and perceptions of BCAA administration, including adherence and possible factors that might impact adherence. "Poor adherence" was defined as "not taking the medication appropriately" or "forgetting to take the medication". Overall, 253 patients (or representatives) completed the survey, of whom 135 were men, 114 were women, and 148 were ≥70 years old. Most patients (163) were prescribed BCAA for ≥2 years and were using three packs per day. Thirty-two patients did not take their medication appropriately and 69 sometimes forgot to administer it. Weariness of taking the medication (P BCAA in clinical practice. Poor adherence was associated with weariness with taking medication, and the unpleasantness of the medication itself. Patient education from general practitioners and hepatologists combined with adherence counseling from pharmacists may help improve adherence. © 2016 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.

  1. Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study.

    Science.gov (United States)

    Malaguarnera, Mariano; Risino, Corrado; Cammalleri, Lisa; Malaguarnera, Lucia; Astuto, Marinella; Vecchio, Ignazio; Rampello, Liborio

    2009-07-01

    Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. After 60 min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40 mumol PBCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgow's score: 3.60 versus 1.50 score PBCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

  2. Controlled branched-chain amino acids auxotrophy in Listeria monocytogenes allows isoleucine to serve as a host signal and virulence effector.

    Science.gov (United States)

    Brenner, Moran; Lobel, Lior; Borovok, Ilya; Sigal, Nadejda; Herskovits, Anat A

    2018-03-01

    Listeria monocytogenes (Lm) is a saprophyte and intracellular pathogen. Transition to the pathogenic state relies on sensing of host-derived metabolites, yet it remains unclear how these are recognized and how they mediate virulence gene regulation. We previously found that low availability of isoleucine signals Lm to activate the virulent state. This response is dependent on CodY, a global regulator and isoleucine sensor. Isoleucine-bound CodY represses metabolic pathways including branched-chain amino acids (BCAA) biosynthesis, however under BCAA depletion, as occurs during infection, BCAA biosynthesis is upregulated and isoleucine-unbound CodY activates virulence genes. While isoleucine was revealed as an important input signal, it was not identified how internal levels are controlled during infection. Here we show that Lm regulates BCAA biosynthesis via CodY and via a riboregulator located upstream to the BCAA biosynthesis genes, named Rli60. rli60 is transcribed when BCAA levels drop, forming a ribosome-mediated attenuator that cis-regulates the downstream genes according to BCAA supply. Notably, we found that Rli60 restricts BCAA production, essentially starving Lm, a mechanism that is directly linked to virulence, as it controls the internal isoleucine pool and thereby CodY activity. This controlled BCAA auxotrophy likely evolved to enable isoleucine to serve as a host signal and virulence effector.

  3. Relationship between Branched-Chain Amino Acids, Metabolic Syndrome, and Cardiovascular Risk Profile in a Chinese Population: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Wen Hu

    2016-01-01

    Full Text Available Objective. This study aimed to evaluate the relationship between branched-chain amino acids (BCAAs, metabolic syndrome (MS, and other cardiovascular (CV risk factors in middle-aged and elderly Chinese population at high risk for the development of cardiovascular disease (CVD. Methods. 1302 subjects were enrolled from the Huai’an Diabetes Prevention Program. Results. BCAAs levels were positively correlated with MS, its components, and CV risk profile. The odds ratio (OR for MS among subjects in the fourth quartile of BCAAs levels showed a 2.17-fold increase compared with those in the first quartile. BCAAs were independently associated with high Framingham risk score even after adjusting for MS and its components (P<0.0001. Additionally, the OR for high CV risk was 3.20-fold (P<0.0001 in participants in the fourth BCAAs quartile with MS compared with participants in the first BCAAs quartile without MS. Conclusions. Increased BCAAs levels are independent risk factors of MS and CVD in addition to the traditional factors in middle-aged and elderly Chinese population. The development of CVD in MS patients with high level BCAAs is accelerated. Intervention studies are needed to investigate whether the strategy of BCAAs reduction has impacts on endpoints in patients with higher CV risk. This study is registered with ChiCTR-TRC-14005029.

  4. Controlled branched-chain amino acids auxotrophy in Listeria monocytogenes allows isoleucine to serve as a host signal and virulence effector.

    Directory of Open Access Journals (Sweden)

    Moran Brenner

    2018-03-01

    Full Text Available Listeria monocytogenes (Lm is a saprophyte and intracellular pathogen. Transition to the pathogenic state relies on sensing of host-derived metabolites, yet it remains unclear how these are recognized and how they mediate virulence gene regulation. We previously found that low availability of isoleucine signals Lm to activate the virulent state. This response is dependent on CodY, a global regulator and isoleucine sensor. Isoleucine-bound CodY represses metabolic pathways including branched-chain amino acids (BCAA biosynthesis, however under BCAA depletion, as occurs during infection, BCAA biosynthesis is upregulated and isoleucine-unbound CodY activates virulence genes. While isoleucine was revealed as an important input signal, it was not identified how internal levels are controlled during infection. Here we show that Lm regulates BCAA biosynthesis via CodY and via a riboregulator located upstream to the BCAA biosynthesis genes, named Rli60. rli60 is transcribed when BCAA levels drop, forming a ribosome-mediated attenuator that cis-regulates the downstream genes according to BCAA supply. Notably, we found that Rli60 restricts BCAA production, essentially starving Lm, a mechanism that is directly linked to virulence, as it controls the internal isoleucine pool and thereby CodY activity. This controlled BCAA auxotrophy likely evolved to enable isoleucine to serve as a host signal and virulence effector.

  5. A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance

    Science.gov (United States)

    Newgard, Christopher B; An, Jie; Bain, James R; Muehlbauer, Michael J; Stevens, Robert D; Lien, Lillian F; Haqq, Andrea M; Shah, Svati H.; Arlotto, Michelle; Slentz, Cris A; Rochon, James; Gallup, Dianne; Ilkayeva, Olga; Wenner, Brett R; Yancy, William E; Eisenson, Howard; Musante, Gerald; Surwit, Richard; Millington, David S; Butler, Mark D; Svetkey, Laura P

    2009-01-01

    Summary Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA) or standard chow (SC) diets. Despite having reduced food intake and weight gain equivalent to the SC group, HF/BCAA rats were equally insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1(ser307), accumulation of multiple acylcarnitines in muscle, and was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a poor dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance. PMID:19356713

  6. Branched-Chain Amino Acids Ameliorate Fibrosis and Suppress Tumor Growth in a Rat Model of Hepatocellular Carcinoma with Liver Cirrhosis

    Science.gov (United States)

    Cha, Jung Hoon; Bae, Si Hyun; Kim, Hye Lim; Park, Na Ri; Choi, Eun Suk; Jung, Eun Sun; Choi, Jong Young; Yoon, Seung Kew

    2013-01-01

    Purpose Recent studies have revealed that branched-chain amino acids (BCAA) reduce the development of hepatocellular carcinoma (HCC) in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR). The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN)-induced HCC and liver cirrhosis in a rat model. Methods Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight) for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. Results The mean area and number of dysplastic nodules (DNs) and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. Conclusions BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level. PMID:24223741

  7. High concentration of branched-chain amino acids promotes oxidative stress, inflammation and migration of human peripheral blood mononuclear cells via mTORC1 activation.

    Science.gov (United States)

    Zhenyukh, Olha; Civantos, Esther; Ruiz-Ortega, Marta; Sánchez, Maria Soledad; Vázquez, Clotilde; Peiró, Concepción; Egido, Jesús; Mas, Sebastián

    2017-03-01

    Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. In cultured PBMCs, 10mmol/L BCAA increased the production of reactive oxygen species (ROS) via both NADPH oxidase and the mitochondria, and activated Akt-mTOR signalling. By using several inhibitors and activators of these molecular pathways we have described that mTOR activation by BCAA is linked to ROS production and mitochondrial dysfunction. BCAA stimulated the activation of the redox-sensitive transcription factor NF-κB, which resulted in the release of pro-inflammatory molecules, such as interleukin-6, tumor necrosis factor-α, intracellular adhesion molecule-1 or CD40L, and the migration of PBMCs. In conclusion, elevated BCAA blood levels can promote the activation of circulating PBMCs, by a mechanism that involving ROS production and NF-κB pathway activation. These data suggest that high concentrations of BCAA could exert deleterious effects on circulating blood cells and therefore contribute to the pro-inflammatory and oxidative status observed in several pathophysiological conditions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Branched-chain amino acids ameliorate fibrosis and suppress tumor growth in a rat model of hepatocellular carcinoma with liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Jung Hoon Cha

    Full Text Available PURPOSE: Recent studies have revealed that branched-chain amino acids (BCAA reduce the development of hepatocellular carcinoma (HCC in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR. The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN-induced HCC and liver cirrhosis in a rat model. METHODS: Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. RESULTS: The mean area and number of dysplastic nodules (DNs and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. CONCLUSIONS: BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level.

  9. Metabolic reconstructions identify plant 3-methylglutaconyl-CoA hydratase that is crucial for branched-chain amino acid catabolism in mitochondria.

    Science.gov (United States)

    Latimer, Scott; Li, Yubing; Nguyen, Thuong T H; Soubeyrand, Eric; Fatihi, Abdelhak; Elowsky, Christian G; Block, Anna; Pichersky, Eran; Basset, Gilles J

    2018-05-09

    The proteinogenic branched-chain amino acids (BCAAs) leucine, isoleucine and valine are essential nutrients for mammals. In plants, BCAAs double as alternative energy sources when carbohydrates become limiting, the catabolism of BCAAs providing electrons to the respiratory chain and intermediates to the tricarboxylic acid cycle. Yet, the actual architecture of the degradation pathways of BCAAs is not well understood. In this study, gene network modeling in Arabidopsis and rice, and plant-prokaryote comparative genomics detected candidates for 3-methylglutaconyl-CoA hydratase (4.2.1.18), one of the missing plant enzymes of leucine catabolism. Alignments of these protein candidates sampled from various spermatophytes revealed non-homologous N-terminal extensions that are lacking in their bacterial counterparts, and green fluorescent protein-fusion experiments demonstrated that the Arabidopsis protein, product of gene At4g16800, is targeted to mitochondria. Recombinant At4g16800 catalyzed the dehydration of 3-hydroxymethylglutaryl-CoA into 3-methylglutaconyl-CoA, and displayed kinetic features similar to those of its prokaryotic homolog. When at4g16800 knockout plants were subjected to dark-induced carbon starvation, their rosette leaves displayed accelerated senescence as compared to control plants, and this phenotype was paralleled by a marked increase in the accumulation of free and total leucine, isoleucine and valine. The seeds of the at4g16800 mutant showed a similar accumulation of free BCAAs. These data suggest that 3-methylglutaconyl-CoA hydratase is not solely involved in the degradation of leucine, but is also a significant contributor to that of isoleucine and valine. Furthermore, evidence is shown that unlike the situation observed in Trypanosomatidae, leucine catabolism does not contribute to the formation of the terpenoid precursor mevalonate. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights

  10. Partial amino acid sequence of the branched chain amino acid aminotransferase (TmB) of E. coli JA199 pDU11

    International Nuclear Information System (INIS)

    Feild, M.J.; Armstrong, F.B.

    1987-01-01

    E. coli JA199 pDU11 harbors a multicopy plasmid containing the ilv GEDAY gene cluster of S. typhimurium. TmB, gene product of ilv E, was purified, crystallized, and subjected to Edman degradation using a gas phase sequencer. The intact protein yielded an amino terminal 31 residue sequence. Both carboxymethylated apoenzyme and [ 3 H]-NaBH-reduced holoenzyme were then subjected to digestion by trypsin. The digests were fractionated using reversed phase HPLC, and the peptides isolated were sequenced. The borohydride-treated holoenzyme was used to isolate the cofactor-binding peptide. The peptide is 27 residues long and a comparison with known sequences of other aminotransferases revealed limited homology. Peptides accounting for 211 of 288 predicted residues have been sequenced, including 9 residues of the carboxyl terminus. Comparison of peptides with the inferred amino acid sequence of the E. coli K-12 enzyme has helped determine the sequence of the amino terminal 59 residues; only two differences between the sequences are noted in this region

  11. Effects of dietary valine:lysine ratio on the performance, amino acid composition of tissues and mRNA expression of genes involved in branched-chain amino acid metabolism of weaned piglets

    Directory of Open Access Journals (Sweden)

    Ye Tong Xu

    2018-01-01

    Full Text Available Objective The goal of this study was to investigate the effects of dietary standard ileal digestible (SID valine:lysine ratios on performance, intestinal morphology, amino acids of liver and muscle, plasma indices and mRNA expression of branched-chain amino acid (BCAA metabolism enzymes. Methods A total of 144 crossbred pigs (Duroc×Landrace×Large White weaned at 28±4 days of age (8.79±0.02 kg body weight were randomly allotted to 1 of 4 diets formulated to provide SID valine:lysine ratios of 50%, 60%, 70%, or 80%. Each diet was fed to 6 pens of pigs with 6 pigs per pen (3 gilts and 3 barrows for 28 days. Results Average daily gain increased quadratically (p<0.05, the villous height of the duodenum, jejunum and ileum increased linearly (p<0.05 as the SID valine:lysine ratio increased. The concentrations of plasma α-keto isovaleric and valine increased linearly (p<0.05, plasma aspartate, asparagine and cysteine decreased (p<0.05 as the SID valine:lysine ratio increased. An increase in SID lysine:valine levels increased mRNA expression levels of mitochondrial BCAA transaminase and branched-chain α-keto acid dehydrogenase in the longissimus dorsi muscle (p<0.05. Conclusion Using a quadratic model, a SID valine:lysine ratio of 68% was shown to maximize the growth of weaned pigs which is slightly higher than the level recommended by the National Research Council [6].

  12. Discriminative Ability of Plasma Branched-Chain Amino Acid Levels for Glucose Intolerance in Families At Risk for Type 2 Diabetes.

    Science.gov (United States)

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Verhoeven, Adrie J M; Langendonk, Janneke G; Rietveld, Trinet; Isaacs, Aaron J; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-04-01

    Insulin resistance and glucose intolerance have been associated with increased plasma levels of branched-chain amino acids (BCAA). BCAA levels do not predict T2DM in the population. We determined the discriminative ability of fasting BCAA levels for glucose intolerance in nondiabetic relatives of patients with T2DM of two different ethnicities. Based on oral glucose tolerance test (OGTT), first-degree relatives of patients with T2DM were categorized as normal glucose tolerance, prediabetes, or T2DM. Included were 34, 12, and 18 Caucasian and 22, 12, and 23 Asian Indian participants, respectively. BCAA levels were measured in fasting plasma together with alanine, phenylalanine, and tyrosine. Insulin sensitivity and beta-cell function were assessed by indices derived from an extended OGTT and their relationship with plasma BCAA levels was assessed in multivariate regression analysis. The value of the amino acids for discriminating prediabetes among nondiabetic family members was determined with the area under the curve of receiver-operated characteristics (c-index). BCAA levels were higher in diabetic than in normoglycemic family members in the Caucasians (P = 0.001) but not in the Asian Indians. In both groups, BCAA levels were associated with waist-hip ratio (β = 0.31; P = 0.03 and β = 0.42; P = 0.001, respectively) but not with indices of insulin sensitivity or beta-cell function. The c-index of BCAA for discriminating prediabetes among nondiabetic participants was 0.83 and 0.74 in Caucasians and Asian Indians, respectively, which increased to 0.84 and 0.79 by also including the other amino acids. The c-index of fasting glucose for discriminating prediabetes increased from 0.91 to 0.92 in Caucasians and 0.85 to 0.97 (P = 0.04) in Asian Indians by inclusion of BCAA+alanine, phenylalanine, and tyrosine. Adding fasting plasma BCAA levels, combined with phenylalanine, tyrosine and alanine to fasting glucose improved discriminative ability for the prediabetic state

  13. Branched-chain Amino Acids are Beneficial to Maintain Growth Performance and Intestinal Immune-related Function in Weaned Piglets Fed Protein Restricted Diet

    Directory of Open Access Journals (Sweden)

    M. Ren

    2015-12-01

    Full Text Available As a novel approach for disease control and prevention, nutritional modulation of the intestinal health has been proved. However, It is still unknown whether branched-chain amino acid (BCAA is needed to maintain intestinal immune-related function. The objective of this study was to determine whether BCAA supplementation in protein restricted diet affects growth performance, intestinal barrier function and modulates post-weaning gut disorders. One hundred and eight weaned piglets (7.96±0.26 kg were randomly fed one of the three diets including a control diet (21% crude protein [CP], CON, a protein restricted diet (17% CP, PR and a BCAA diet (BCAA supplementation in the PR diet for 14 d. The growth performance, plasma amino acid concentrations, small intestinal morphology and intestinal immunoglobulins were tested. First, average daily gain (ADG (p0.05. The PR and BCAA treatments had a higher (p<0.05 plasma concentration of methionine and threonine than the CON treatment. The level of some essential and functional amino acids (such as arginine, phenylalanine, histidine, glutamine etc. in plasma of the PR group was lower (p<0.05 than that of the CON group. Compared with CON group, BCAA supplementation significantly increased BCAA concentrations (p<0.01 and decreased urea concentration (p<0.01 in pig plasma indicating that the efficiency of dietary nitrogen utilization was increased. Compared with CON group, the small intestine of piglets fed PR diet showed villous atrophy, increasing of intra-epithelial lymphocytes (IELs number (p<0.05 and declining of the immunoglobulin concentration, including jejunal immunoglobulin A (IgA (p = 0.04, secreted IgA (sIgA (p = 0.03 and immunoglobulin M (p = 0.08, and ileal IgA (p = 0.01 and immunoglobulin G (p = 0.08. The BCAA supplementation increased villous height in the duodenum (p<0.01, reversed the trend of an increasing IELs number. Notably, BCAA supplementation increased levels of jejunal and ileal

  14. In silico designing of therapeutic protein enriched with branched-chain amino acids for the dietary treatment of chronic liver disease.

    Science.gov (United States)

    L, Sunil; Vasu, Prasanna

    2017-09-01

    Leucine, isoleucine, and valine are three essential branched-chain amino acids (BCAA) account for 40-45% of total essential amino acids. BCAA stimulates protein synthesis primarily in skeletal muscles, and it can directly transport to circulatory blood stream bypassing the liver. Hence, a protein enriched with BCAA is an important therapeutic target for the dietary treatment of chronic liver disease. The present study is to design a synthetic protein enriched with BCAA and the challenge is to maximize the BCAA content, keeping the balanced ratio of leucine, isoleucine, valine - 2: 1: 1.2 as specified by WHO/UNU/FAO. Here, we turned the general concept of homology modeling and tried to find a suitable scaffold (α-helix) to host an excess amount of BCAA for increased stability and digestibility. A total of 50 protein models were constructed by using SWISS-MODEL, Modeller 9.17, ProtParam tool, and allergen online tools. Out of 50 different protein models, protein model-50 was found to be best, which had a well-defined 3D structure, good in silico digestibility, balanced ratio of BCAA and showed 65.57% structure identity to the template apo-bovine α-lactalbumin (1F6R). Templates search was performed against PDB using PSI-BLAST, SWISS-MODEL, PROFUNC, I-TASSER, and ConSurf. The secondary structure was predicted by PSSPred, PSIPRED, I-TASSER, PORTER, and SPIDER2. The modeled structure of protein Model-50 was validated by PROCHECK, ERRAT, ProSA, and QMEAN. COACH and ProFUNC tools were performed to determine the functional effects of protein model-50. Overall, the BCAA was enriched from 22 to 56.4% with the balanced ratio of Leu: Ile: Val (2: 1: 1.2). The Ramachandran plot showed 97.7% of the amino acid residues in allowed regions with ERRAT score of 86.05. We have successfully modeled the complete three-dimensional structure of the target protein model-50 using highly reputed computational tools. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Branched-chain amino acid interactions with reference to amino acid requirements in adult men: Valine metabolism at different leucine intakes

    International Nuclear Information System (INIS)

    Pelletier, V.; Marks, L.; Wagner, D.A.; Hoerr, R.A.; Young, V.R.

    1991-01-01

    The authors explored whether the oxidation of valine and by implication the physiological requirement for this amino acid are affected by changes in leucine intake over a physiological range. Six young adult men received, in random order, four L-amino acid-based diets for 5 d supplying either 20 or 10 mg valine.kg body wt-1.d-1, each in combination with 80 or 40 mg leucine.kg-1.d-1. On day 6 subjects were studied with an 8-h continuous intravenous infusion of [1-13C]valine (and [2H3]leucine) to determine valine oxidation in the fasted state (first 3 h) and fed state (last 5 h). Valine oxidation in the fasted state was similar among all diets but was lower (P less than 0.05) in the fed state for the 10 vs 20 mg valine.kg-1.d-1 intake. Leucine intake did not affect valine oxidation. Mean daily valine balance approximated +1.3 mg.kg-1.d-1 for the 20-mg intake and -1.6 mg.kg-1.d-1 for the 10-mg intake. These findings support our previously suggested mean valine requirement estimate of approximately 20 mg.kg-1.d-1

  16. Analysis of the LIV System of Campylobacter jejuni Reveals Alternative Roles for LivJ and LivK in Commensalism beyond Branched-Chain Amino Acid Transport ▿

    Science.gov (United States)

    Ribardo, Deborah A.; Hendrixson, David R.

    2011-01-01

    Campylobacter jejuni is a leading cause of diarrheal disease in humans and an intestinal commensal in poultry and other agriculturally important animals. These zoonotic infections result in significant amounts of C. jejuni present in the food supply to contribute to disease in humans. We previously found that a transposon insertion in Cjj81176_1038, encoding a homolog of the Escherichia coli LivJ periplasmic binding protein of the leucine, isoleucine, and valine (LIV) branched-chain amino acid transport system, reduced the commensal colonization capacity of C. jejuni 81-176 in chicks. Cjj81176_1038 is the first gene of a six-gene locus that encodes homologous components of the E. coli LIV system. By analyzing mutants with in-frame deletions of individual genes or pairs of genes, we found that this system constitutes a LIV transport system in C. jejuni responsible for a high level of leucine acquisition and, to a lesser extent, isoleucine and valine acquisition. Despite each LIV protein being required for branched-chain amino acid transport, only the LivJ and LivK periplasmic binding proteins were required for wild-type levels of commensal colonization of chicks. All LIV permease and ATPase components were dispensable for in vivo growth. These results suggest that the biological functions of LivJ and LivK for colonization are more complex than previously hypothesized and extend beyond a role for binding and acquiring branched-chain amino acids during commensalism. In contrast to other studies indicating a requirement and utilization of other specific amino acids for colonization, acquisition of branched-chain amino acids does not appear to be a determinant for C. jejuni during commensalism. PMID:21949065

  17. Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

    Science.gov (United States)

    Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

    2017-04-01

    For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model.

    Science.gov (United States)

    Takegoshi, Kai; Honda, Masao; Okada, Hikari; Takabatake, Riuta; Matsuzawa-Nagata, Naoto; Campbell, Jean S; Nishikawa, Masashi; Shimakami, Tetsuro; Shirasaki, Takayoshi; Sakai, Yoshio; Yamashita, Taro; Takamura, Toshinari; Tanaka, Takuji; Kaneko, Shuichi

    2017-03-14

    Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks. BCAA supplementation significantly improved hepatic steatosis, inflammation, fibrosis, and tumors in Ath+HF mice at 68 weeks. GeneChip analysis demonstrated the significant resolution of pro-fibrotic gene expression by BCAA supplementation. The anti-fibrotic effect of BCAA was confirmed further using platelet-derived growth factor C transgenic mice, which develop hepatic fibrosis and tumors. In vitro, BCAA restored the transforming growth factor (TGF)-β1-stimulated expression of pro-fibrotic genes in hepatic stellate cells (HSC). In hepatocytes, BCAA restored TGF-β1-induced apoptosis, lipogenesis, and Wnt/β-Catenin signaling, and inhibited the transformation of WB-F344 rat liver epithelial stem-like cells. BCAA repressed the promoter activity of TGFβ1R1 by inhibiting the expression of the transcription factor NFY and histone acetyltransferase p300. Interestingly, the inhibitory effect of BCAA on TGF-β1 signaling was mTORC1 activity-dependent, suggesting the presence of negative feedback regulation from mTORC1 to TGF-β1 signaling. Thus, BCAA induce an anti-fibrotic effect in HSC, prevent apoptosis in hepatocytes, and decrease the incidence of HCC; therefore, BCAA supplementation would be beneficial for patients with advanced liver fibrosis with a high risk of HCC.

  19. Effects of carbohydrate and branched-chain amino acid beverage ingestion during acute upper body resistance exercise on performance and postexercise hormone response.

    Science.gov (United States)

    Smith, JohnEric W; Krings, Ben M; Shepherd, Brandon D; Waldman, Hunter S; Basham, Steven A; McAllister, Matthew J

    2018-05-01

    The purpose of this investigation was to examine the individual and combined effects of ingesting carbohydrates (CHO) and branched-chain amino acids (BCAA) during high-volume upper body resistance exercise (RE) on markers of catabolism and performance. Thirteen resistance-trained males completed 4 experimental trials with supplementation, ingesting beverages containing CHO, BCAA, CHO+BCAA, or placebo (PLA) in a randomized, double-blind design. The beverages were ingested in 118-mL servings 6 times during an ∼60-min RE session consisting of bench press, bent-over row, incline press, and close-grip row. Each RE was performed with 5 sets of repetitions at 65% 1-repetition maximum until volitional fatigue. Blood samples were collected at baseline, immediately postexercise, and 60 min postexercise to assess glucose and insulin. Cortisol was assessed immediately and at 60 min postexercise. No significant performance benefits were observed for any RE. CHO+BCAA (152.4 ± 71.4 ng/mL) resulted in the lowest cortisol levels, which was lower than BCAA and PLA (193.7 ± 88.5, 182.8 ± 67.5 ng/mL, p BCAA and PLA (3.7 ± 2.0, 3.5 ± 1.8 mU/L, p BCAA (4.3 ± 2.5 mU/L, p = 0.339). There was no treatment effect for glucose, but glucose significantly increased from baseline to immediately postexercise and significantly decreased at 60 min postexercise. Ingesting beverages containing CHO with or without BCAA during upper body resistance exercise may promote a more favorable postexercise less catabolic environment.

  20. A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kikuchi, Yutaro; Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Murakami, Takashi; Yabushita, Yasuhiro; Endo, Itaru; Taguri, Masataka; Koda, Keiji; Tanaka, Kuniya

    2016-10-01

    Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].

  1. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Science.gov (United States)

    Everman, Sarah; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

    2015-01-01

    Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion. Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile - 3rd quartile)] between Control and BCAA in either the 40U ([199 (167-278) vs. 186 (94-308)] or 80 U ([491 (414-548) vs. 478 (409-857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P BCAA in either of the experiments (P > 0.05). Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  2. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.

    Science.gov (United States)

    Connelly, Margery A; Wolak-Dinsmore, Justyna; Dullaart, Robin P F

    2017-05-01

    Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance. BCAA were measured by nuclear magnetic resonance, whereas leptin and adiponectin were measured by immunoassay, in subjects with normal fasting glucose (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15). Insulin resistance was estimated by homeostasis model assessment (HOMAir). BCAA were higher in men than in women (P BCAA were correlated with HOMAir (r = 0.46; P  0.05). Multivariable linear regression analysis, adjusting for age, sex, T2DM, and body mass index (BMI), demonstrated that BCAA were positively associated with HOMAir (β = 0.242, P = 0.023). When BCAA, leptin, and adiponectin were included together, the positive relationship of HOMAir with BCAA (β = 0.275, P = 0.012) remained significant. Insulin resistance was associated with BCAA. This association remained after adjusting for age, sex, T2DM, BMI, as well as leptin and adiponectin. It is unlikely that the relationship of insulin resistance with BCAA is to a major extent attributable to effects of leptin and adiponectin.

  3. Branched-Chain Amino Acids and Arginine Improve Performance in Two Consecutive Days of Simulated Handball Games in Male and Female Athletes: A Randomized Trial

    Science.gov (United States)

    Chang, Chen-Kang; Chang Chien, Kun-Ming; Chang, Jung-Hsien; Huang, Mei-Hsuan; Liang, Ya-Chuan; Liu, Tsung-Han

    2015-01-01

    The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days. Methods: Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34±0.60%, PB trial: -0.21±0.69%; second half: AA trial: -1.68±0.58%, PB trial: 0.49±0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2±0.3) than the PB trial (15.1±0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue. PMID:25803783

  4. Influence of supplementation with branched-chain amino acids in combination with resistance exercise on p70S6 kinase phosphorylation in resting and exercising human skeletal muscle.

    Science.gov (United States)

    Apró, W; Blomstrand, E

    2010-11-01

    Skeletal muscle growth is thought to be regulated by the mammalian target of rapamycin (mTOR) pathway, which can be activated by resistance exercise and branched-chain amino acids (BCAA). The major aim of the present study was to distinguish between the influence of resistance exercise and BCAA on key enzymes considered to be involved in the regulation of protein synthesis, including p70(S6) kinase (p70(S6k)). Nine healthy subjects (four men and five women) performed unilateral resistance exercise on two occasions separated by 1 month. Subjects were randomly supplied either a mixture of BCAA or flavoured water. Muscle biopsies were taken from both resting and exercising muscle before, after and 1 h after exercise. Phosphorylation of Akt was unaltered by either resistance exercise and/or BCAA supplementation whereas mTOR phosphorylation was enhanced (Pexercising and resting muscle following exercise in the absence (70-90%) and presence of BCAA supplementation (80-130%). Phosphorylation of p70(S6k) was unaffected by resistance exercise alone; however, BCAA intake increased (Pexercise. In resting muscle, a 5- and 16-fold increase in p70(S6k) was observed immediately after and 1 h after exercise, respectively, as compared to 11- and 30-fold increases in the exercising muscle. Phosphorylation of eukaryotic elongation factor 2 was attenuated 1 h after exercise (Pexercising muscle (30-50%) under both conditions. The present findings indicate that resistance exercise and BCAA exert both separate and combined effects on the p70(S6k) phosphorylation in an Akt-independent manner. © 2010 The Authors. Journal compilation © 2010 Scandinavian Physiological Society.

  5. Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

    Science.gov (United States)

    Qiu, Jun; Wang, Jinhao; Xu, Zhongqi; Liu, Huiqing; Ren, Jie

    2017-01-01

    The branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE) coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val) were separated in a background electrolyte (BGE) consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD) at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS) as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections) of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations) of migration time and peak area were less than 0.91% and 3.66% (n = 6). Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

  6. Exercise-induced muscle damage is reduced in resistance-trained males by branched chain amino acids: a randomized, double-blind, placebo controlled study

    Directory of Open Access Journals (Sweden)

    Howatson Glyn

    2012-07-01

    Full Text Available Abstract Background It is well documented that exercise-induced muscle damage (EIMD decreases muscle function and causes soreness and discomfort. Branched-chain amino acid (BCAA supplementation has been shown to increase protein synthesis and decrease muscle protein breakdown, however, the effects of BCAAs on recovery from damaging resistance training are unclear. Therefore, the aim of this study was to examine the effects of a BCAA supplementation on markers of muscle damage elicited via a sport specific bout of damaging exercise in trained volunteers. Methods Twelve males (mean ± SD age, 23 ± 2 y; stature, 178.3 ± 3.6 cm and body mass, 79.6 ± 8.4 kg were randomly assigned to a supplement (n = 6 or placebo (n = 6 group. The damaging exercise consisted of 100 consecutive drop-jumps. Creatine kinase (CK, maximal voluntary contraction (MVC, muscle soreness (DOMS, vertical jump (VJ, thigh circumference (TC and calf circumference (CC were measured as markers of muscle damage. All variables were measured immediately before the damaging exercise and at 24, 48, 72 and 96 h post-exercise. Results A significant time effect was seen for all variables. There were significant group effects showing a reduction in CK efflux and muscle soreness in the BCAA group compared to the placebo (P Conclusion The present study has shown that BCAA administered before and following damaging resistance exercise reduces indices of muscle damage and accelerates recovery in resistance-trained males. It seems likely that BCAA provided greater bioavailablity of substrate to improve protein synthesis and thereby the extent of secondary muscle damage associated with strenuous resistance exercise. Clinical Trial Registration Number: NCT01529281.

  7. The effects of acute branched-chain amino acid supplementation on recovery from a single bout of hypertrophy exercise in resistance-trained athletes.

    Science.gov (United States)

    Waldron, Mark; Whelan, Kieran; Jeffries, Owen; Burt, Dean; Howe, Louis; Patterson, Stephen David

    2017-06-01

    This study investigated the effects of acute branched-chain amino acid (BCAA) supplementation on recovery from exercise-induced muscle damage among experienced resistance-trained athletes. In a double-blind matched-pairs design, 16 resistance-trained participants, routinely performing hypertrophy training, were randomly assigned to a BCAA (n = 8) or placebo (n = 8) group. The BCAAs were administered at a dosage of 0.087 g/kg body mass, with a 2:1:1 ratio of leucine, isoleucine, and valine. The participants performed 6 sets of 10 full-squats at 70% 1-repetition maximum to induce muscle damage. All participants were diet-controlled across the study. Creatine kinase, peak isometric knee-extensor force, perceived muscle soreness, and countermovement jump (CMJ) height were measured immediately before (baseline) and at 1 h, 24 h, and 48 h postexercise. There were large to very large time effects for all measurements between baseline and 24-48 h. Between-group comparisons, expressed as a percentage of baseline, revealed differences in isometric strength at 24-h (placebo ∼87% vs. BCAA ∼92%; moderate, likely), CMJ at 24 h (placebo ∼93% vs. BCAA ∼96%; small, likely), and muscle soreness at both 24 h (placebo ∼685% vs. BCAA ∼531%; small, likely) and 48 h (placebo ∼468% vs. BCAA ∼350%; small, likely). Acute supplementation of BCAAs (0.087 g/kg) increased the rate of recovery in isometric strength, CMJ height, and perceived muscle soreness compared with placebo after a hypertrophy-based training session among diet-controlled, resistance-trained athletes. These findings question the need for longer BCAA loading phases and highlight the importance of dietary control in studies of this type.

  8. Effects of Diets Supplemented with Branched-Chain Amino Acids on the Performance and Fatigue Mechanisms of Rats Submitted to Prolonged Physical Exercise

    Directory of Open Access Journals (Sweden)

    Inar Alves de Castro

    2012-11-01

    Full Text Available This study aimed to determine the effects of diets chronically supplemented with branched-chain amino acids (BCAA on the fatigue mechanisms of trained rats. Thirty-six adult Wistar rats were trained for six weeks. The training protocol consisted of bouts of swimming exercise (one hour a day, five times a week, for six weeks. The animals received a control diet (C (n = 12, a diet supplemented with 3.57% BCAA (S1 (n = 12, or a diet supplemented with 4.76% BCAA (S2 (n = 12. On the last day of the training protocol, half the animals in each group were sacrificed after one hour of swimming (1H, and the other half after a swimming exhaustion test (EX. Swimming time until exhaustion was increased by 37% in group S1 and reduced by 43% in group S2 compared to group C. Results indicate that the S1 diet had a beneficial effect on performance by sparing glycogen in the soleus muscle (p < 0.05 and by inducing a lower concentration of plasma ammonia, whereas the S2 diet had a negative effect on performance due to hyperammonemia (p < 0.05. The hypothalamic concentration of serotonin was not significantly different between the 1H and EX conditions. In conclusion, chronic BCAA supplementation led to increased performance in rats subjected to a swimming test to exhaustion. However, this is a dose-dependent effect, since chronic ingestion of elevated quantities of BCAA led to a reduction in performance.

  9. Branched-chain amino acids and arginine improve performance in two consecutive days of simulated handball games in male and female athletes: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Chen-Kang Chang

    Full Text Available The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days.Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial, or placebo (PB trial before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34 ± 0.60%, PB trial: -0.21 ± 0.69%; second half: AA trial: -1.68 ± 0.58%, PB trial: 0.49 ± 0.42%. The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2 ± 0.3 than the PB trial (15.1 ± 0.4. Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue.

  10. Branched-chain amino acids enhance premature senescence through mammalian target of rapamycin complex I-mediated upregulation of p21 protein.

    Directory of Open Access Journals (Sweden)

    Masayuki Nakano

    Full Text Available Branched-chain amino acids (BCAAs have been applied as an oral supplementation to patients with liver cirrhosis. BCAAs not only improve nutritional status of patients but also decrease the incidence of liver cancer. Mammalian target of rapamycin (mTOR links cellular metabolism with growth and proliferation in response to nutrients, energy, and growth factors. BCAAs, especially leucine, have been shown to regulate protein synthesis through mTOR activities. On the other hand, cellular senescence is suggested to function as tumor suppressor mechanisms, and induced by a variety of stimuli including DNA damage-inducing drugs. However, it is not clear how BCAA supplementation prevents the incidence of liver cancer in patients with cirrhosis. Here we showed that human cancer cells, HepG2 and U2OS, cultured in medium containing BCAAs with Fischer's ratio about 3, which was shown to have highest activities to synthesize and secrete of albumin, had higher activities to induce premature senescence and elevate mTORC1 activities. Furthermore, BCAAs themselves enhanced the execution of premature senescence induced by DNA damage-inducing drugs, which was effectively prevented by rapamycin. These results strongly suggested the contribution of the mTORC1 pathway to the regulation of premature senescence. Interestingly, the protein levels of p21, a p53 target and well-known gene essential for the execution of cellular senescence, were upregulated in the presence of BCAAs. These results suggested that BCAAs possibly contribute to tumor suppression by enhancing cellular senescence mediated through the mTOR signalling pathway.

  11. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Directory of Open Access Journals (Sweden)

    Sarah Everman

    Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  12. The Defense-Related Isoleucic Acid Differentially Accumulates in Arabidopsis Among Branched-Chain Amino Acid-Related 2-Hydroxy Carboxylic Acids

    Directory of Open Access Journals (Sweden)

    Rafał P. Maksym

    2018-06-01

    Full Text Available The branched-chain amino acid (BCAA related 2-hydroxy carboxylic acid isoleucic acid (ILA enhances salicylic acid-mediated pathogen defense in Arabidopsis thaliana. ILA has been identified in A. thaliana as its glucose conjugate correlated with the activity of the small-molecule glucosyltransferase UGT76B1, which can glucosylate both salicylic acid and ILA in vitro. However, endogenous levels of the ILA aglycon have not yet been determined in planta. To quantify ILA as well as the related leucic acid (LA and valic acid (VA in plant extracts, a sensitive method based on the derivatization of small carboxylic acids by silylation and gas chromatography–mass spectrometric analysis was developed. ILA was present in all species tested including several monocotyledonous and dicotyledonous plants as well as broadleaf and coniferous trees, whereas LA and VA were only detectable in a few species. In A. thaliana both ILA and LA were found. However, their levels varied during plant growth and in root vs. leaves. ILA levels were higher in 2-week-old leaves and decreased in older plants, whereas LA exhibited a reverted accumulation pattern. Roots displayed higher ILA and LA levels compared to leaves. ILA was inversely related to UGT76B1 expression level indicating that UGT76B1 glucosylates ILA in planta. In contrast, LA was not affected by the expression of UGT76B1. To address the relation of both 2-hydroxy acids to plant defense, we studied ILA and LA levels upon infection by Pseudomonas syringae. LA abundance remained unaffected, whereas ILA was reduced. This change suggests an ILA-related attenuation of the salicylic acid response. Collectively, the BCAA-related ILA and LA differentially accumulated in Arabidopsis, supporting a specific role and regulation of the defense-modulating small-molecule ILA among these 2-hydroxy acids. The new sensitive method will pave the way to further unravel their role in plants.

  13. Branched chain amino acids maintain the molecular weight of poly(γ-glutamic acid) of Bacillus licheniformis ATCC 9945 during the fermentation.

    Science.gov (United States)

    Mitsunaga, Hitoshi; Meissner, Lena; Büchs, Jochen; Fukusaki, Eiichiro

    2016-10-01

    Poly(γ-glutamic acid) mainly produced by Bacillus spp. is an industrially important compound due to several useful features. Among them, molecular weight is an important characteristic affecting on the physical properties such as viscosities and negative charge densities. However, it is difficult to control the molecular size of PGA since it decreases during fermentation. Previous study reported that PGA produced in the media containing different carbon sources such as glucose and glycerol showed differences in molecular weight. Therefore in this study, the effect of carbon source on the PGA molecular weight was examined; with the aim of developing a strategy to maintain the high molecular weight of PGA during fermentation. Our result showed that the weight average molecular weight (Mw) of PGA of Bacillus licheniformis ATCC 9945 cultivated in the media containing PTS-sugars were higher than the medium containing glycerol (non-PTS). The result of metabolome analysis indicated the possibility of CodY (a global regulator protein) activation in the cells cultivated in the media containing PTS-sugars. To mimic this effect, branched-chain amino acids (BCAAs), which are activators of CodY, were added to a medium containing glycerol. As the result, the Mw of PGA in the BCAAs-supplemented media were maintained and high during the early production phase compared to the non BCAAs-supplemented medium. These results indicate that BCAAs can repress the PGA molecular weight reduction during fermentation in B. licheniformis ATCC 9945. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

    Directory of Open Access Journals (Sweden)

    Jun Qiu

    Full Text Available The branched-chain amino acids (BCAAs including leucine (Leu, isoleucine (Ile and valine (Val play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val were separated in a background electrolyte (BGE consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations of migration time and peak area were less than 0.91% and 3.66% (n = 6. Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

  15. Regulation of adipose branched-chain amin acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

    Science.gov (United States)

    Elevated blood branched-chain amin acids (BCAA)are often assoicated with insulin resistance and type2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metaboli...

  16. Determination of branched chain amino acids, methionine, phenylalanine, tyrosine and alpha-keto acids in plasma and dried blood samples using HPLC with fluorescence detection.

    Science.gov (United States)

    Kand'ár, Roman; Záková, Pavla; Jirosová, Jana; Sladká, Michaela

    2009-01-01

    The determination of branched chain amino acids [BCAA; valine (Val), leucine (Leu), isoleucine (Ile)], alpha-keto acids derived from BCAA [BCKA; alpha-ketoisovaleric acid (KIV), alpha-ketoisocaproic acid (KIC), alpha-ketomethylvaleric acid (KMV)], methionine (Met), phenylalanine (Phe) and tyrosine (Tyr) is currently the most reliable approach for the diagnosis of maple syrup urine disease (MSUD), hypermethioninemia, phenylketonuria (PKU) and tyrosinemia. The aim of this study was to develop rapid and simple HPLC methods for measurement of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples. Samples of peripheral venous blood with EDTA as anticoagulant were obtained from a group of healthy blood donors (n=70, 35 females, 27-41 years of age and 35 males, 28-43 years of age). Blood-spot samples from a group of newborns (n=80, 40 girls and 40 boys 3-5 days of age) were collected onto #903 Specimen Collection Paper and allowed to dry for at least 24 h before analysis. Prior to separation, the amino acids (AA) were derivatized with o-phthaldialdehyde (OPA) and BCKA with o-phenylenediamine (OPD). Reverse phase column chromatography (LiChroCart 125-4 Purospher RP-18e, 5 microm) was used for separation and fluorescence detection used to monitoring of effluent. For AA analysis, 25 mmol/L sodium hydrogenphosphate-methanol (90:10, v/v), pH 6.5+/-0.1 was used as mobile phase A and 100% methanol was used as mobile phase B. Measurement of BCKA used a mixture of methanol and deionized water (55:45, v/v) as mobile phase A and mobile phase B consisted of 100% methanol. Analytical performance of these methods was satisfactory for the determination of all AA and BCKA. The intra-assay and inter-assay coefficients of variation were below 10% and recovery ranged from 90%-110%. We have developed simple, rapid and selective HPLC methods with fluorescence detection for the determination of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples.

  17. Supplementation of branched-chain amino acids in protein-restricted diets modulates the expression levels of amino acid transporters and energy metabolism associated regulators in the adipose tissue of growing pigs

    Directory of Open Access Journals (Sweden)

    Yinghui Li

    2016-03-01

    Full Text Available This experiment was conducted to investigate the effects of branched-chain amino acids (BCAA supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue (WAT of different regional depots including dorsal subcutaneous adipose (DSA and abdominal subcutaneous adipose (ASA. A total of 24 crossbred barrows (7.40 ± 0.70 kg were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1 a recommended adequate protein diet (AP, 20% CP, as a positive control; 2 a low protein diet (LP, 17% CP; 3 the LP diet supplemented with BCAA (LP + B, 17% CP to reach the same level of the AP diet group; 4 the LP diet supplemented with 2 times the amount of BCAA (LP + 2B, 17% CP. The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments (P  0.05. Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of L-type amino acid transporter 4 in ASA (P < 0.05. Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets (P < 0.05. The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.

  18. [Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy].

    Science.gov (United States)

    Cong, Minghua; Song, Chenxin; Zou, Baohua; Deng, Yingbing; Li, Shuluan; Liu, Xuehui; Liu, Weiwei; Liu, Jinying; Yu, Lei; Xu, Binghe

    2015-03-17

    To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy. From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched-chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups. After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.

  19. Jugular-infused methionine, lysine and branched-chain amino acids does not improve milk production in Holstein cows experiencing heat stress.

    Science.gov (United States)

    Kassube, K R; Kaufman, J D; Pohler, K G; McFadden, J W; Ríus, A G

    2017-12-01

    Poor utilization of amino acids contributes to losses of milk protein yield in dairy cows exposed to heat stress (HS). Our objective was to test the effect of essential amino acids on milk production in lactating dairy cows exposed to short-term HS conditions. To achieve this objective, 12 multiparous, lactating Holstein cows were assigned to two environments (thermoneutral (THN) or HS) from days 1 to 14 in a split-plot type cross-over design. All cows received 0 g/day of essential amino acids from days 1 to 7 (negative control (NC)) followed by an intravenous infusion of l-methionine (12 g/day), l-lysine (21 g/day), l-leucine (35 g/day), l-isoleucine (15 g/day) and l-valine (15 g/day, methionine, lysine and branched-chain amino acids (ML+BCAA)) from days 8 to 14. The basal diet was composed of ryegrass silage and hay, and a concentrate mix. This diet supplied 44 g of methionine, 125 g of lysine, 167 g of leucine, 98 g of isoleucine and 109 g of valine per day to the small intestine of THN cows. Temperature-humidity index was maintained below 66 for the THN environment, whereas the index was maintained above 68, peaking at 76, for 14 continuous h/day for the HS environment. Heat stress conditioning increased the udder temperature from 37.0°C to 39.6°C. Cows that received the ML+BCAA treatment had greater p.m. rectal and vaginal temperatures (0.50°C and 0.40°C, respectively), and respiration rate (8 breaths/min) compared with those on the NC treatment and exposed to a HS environment. However, neither NC nor ML+BCAA affected rectal or vaginal temperatures and respiration rates in the THN environment. Compared with THN, the HS environment reduced dry matter intake (1.48 kg/day), milk yield (2.82 kg/day) and milk protein yield (0.11 kg/day). However, compared with NC, the ML+BCAA treatment increased milk protein percent by 0.07 points. For the THN environment, the ML+BCAA treatment increased concentrations of milk urea nitrogen. For the HS environment, the ML

  20. Two randomized controlled studies comparing the nutritional benefits of branched-chain amino acid (BCAA) granules and a BCAA-enriched nutrient mixture for patients with esophageal varices after endoscopic treatment

    OpenAIRE

    Sakai, Yoshiyuki; Iwata, Yoshinori; Enomoto, Hirayuki; Saito, Masaki; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Aizawa, Nobuhiro; Ikeda, Naoto; Tanaka, Hironori; Iijima, Hiroko; Nishiguchi, Shuhei

    2014-01-01

    Background The usefulness of branched-chain amino acid (BCAA) granules and BCAA-enriched nutrient mixtures for patients with liver cirrhosis is often reported. However, no randomized controlled studies have investigated the usefulness of these supplements in the nutritional intervention of cirrhotic patients receiving endoscopic treatment for esophageal varices. Methods Patients without BCAA before endoscopic treatment were divided into study 1, and those who received BCAA were divided into s...

  1. Analysis of the LIV System of Campylobacter jejuni Reveals Alternative Roles for LivJ and LivK in Commensalism beyond Branched-Chain Amino Acid Transport ▿

    OpenAIRE

    Ribardo, Deborah A.; Hendrixson, David R.

    2011-01-01

    Campylobacter jejuni is a leading cause of diarrheal disease in humans and an intestinal commensal in poultry and other agriculturally important animals. These zoonotic infections result in significant amounts of C. jejuni present in the food supply to contribute to disease in humans. We previously found that a transposon insertion in Cjj81176_1038, encoding a homolog of the Escherichia coli LivJ periplasmic binding protein of the leucine, isoleucine, and valine (LIV) branched-chain amino aci...

  2. Intact Protein Analysis at 21 Tesla and X-Ray Crystallography Define Structural Differences in Single Amino Acid Variants of Human Mitochondrial Branched-Chain Amino Acid Aminotransferase 2 (BCAT2)

    Science.gov (United States)

    Anderson, Lissa C.; Håkansson, Maria; Walse, Björn; Nilsson, Carol L.

    2017-09-01

    Structural technologies are an essential component in the design of precision therapeutics. Precision medicine entails the development of therapeutics directed toward a designated target protein, with the goal to deliver the right drug to the right patient at the right time. In the field of oncology, protein structural variants are often associated with oncogenic potential. In a previous proteogenomic screen of patient-derived glioblastoma (GBM) tumor materials, we identified a sequence variant of human mitochondrial branched-chain amino acid aminotransferase 2 as a putative factor of resistance of GBM to standard-of-care-treatments. The enzyme generates glutamate, which is neurotoxic. To elucidate structural coordinates that may confer altered substrate binding or activity of the variant BCAT2 T186R, a 45 kDa protein, we applied combined ETD and CID top-down mass spectrometry in a LC-FT-ICR MS at 21 T, and X-Ray crystallography in the study of both the variant and non-variant intact proteins. The combined ETD/CID fragmentation pattern allowed for not only extensive sequence coverage but also confident localization of the amino acid variant to its position in the sequence. The crystallographic experiments confirmed the hypothesis generated by in silico structural homology modeling, that the Lys59 side-chain of BCAT2 may repulse the Arg186 in the variant protein (PDB code: 5MPR), leading to destabilization of the protein dimer and altered enzyme kinetics. Taken together, the MS and novel 3D structural data give us reason to further pursue BCAT2 T186R as a precision drug target in GBM. [Figure not available: see fulltext.

  3. Effect of branched-chain amino acid-enriched nutritional supplementation on interferon therapy in Japanese patients with chronic hepatitis C virus infection: a retrospective study

    Directory of Open Access Journals (Sweden)

    Nagao Yumiko

    2012-11-01

    Full Text Available Abstract Background The aims of this study were to evaluate the effects of nutritional supplementation with branched-chain amino acids (BCAA with zinc component (Aminofeel® on adherence to and outcome of therapy in patients treated with interferon (IFN for chronic hepatitis C and cirrhosis and to determine whether to recommend the supplement. Methods In this retrospective study, 51 patients who received IFN therapy were investigated among 203 consecutive patients who visited our hospital and were advised regarding the potential benefit of taking Aminofeel®. Each patient was free to choose whether to purchase and take Aminofeel®. Results Twenty four patients (group 1-A took Aminofeel® during standard IFN therapy and 13 (group 1-B did not. Low-dose, long-term IFN (maintenance therapy, mainly peglated (Peg-IFN alpha 2a, was administered to 14 patients who were difficult to treat, because of no effect or harmful side effects with standard IFN therapy, and who had advanced liver fibrosis. Among the 14, 11 patients (group 2-A took Aminofeel® and 3 (group 2-B did not. The prevalence of obesity was significantly higher (P=0.04 in group 1-A than in group 1-B. The rate of adherence to IFN therapy was higher in group 1-A (83.3% than in group 1-B (53.8%, P=0.05. There were no significant differences between the two groups in the rates of sustained virological response (SVR to IFN therapy. According to multivariate analysis, two factors, SVR and intake of Aminofeel®, were associated with successful adherence to IFN therapy. The adjusted odds ratios for these two factors were 13.25 and 12.59, respectively, and each was statistically significant. The SVR rate of maintenance IFN therapy was in 18.2% group 2-A and 0% in group 2-B. Conclusion Our data show that BCAA intake is useful for adherence to and effect of IFN therapy for patients with chronic hepatitis C. Nutritional supplementation with BCAA seems to be useful for HCV-infected patients receiving

  4. Novel consortium of Klebsiella variicola and Lactobacillus species enhances the functional potential of fermented dairy products by increasing the availability of branched-chain amino acids and the amount of distinctive volatiles.

    Science.gov (United States)

    Rosales-Bravo, H; Morales-Torres, H C; Vázquez-Martínez, J; Molina-Torres, J; Olalde-Portugal, V; Partida-Martínez, L P

    2017-11-01

    Identify novel bacterial taxa that could increase the availability of branched-chain amino acids and the amount of distinctive volatiles during skim milk fermentation. We recovered 344 bacterial isolates from stool samples of healthy and breastfed infants. Five were selected based on their ability to produce branched-chain amino acids. Three strains were identified as Escherichia coli, one as Klebsiella pneumoniae and other as Klebsiella variicola by molecular and biochemical methods. HPLC and solid-phase microextraction with GC-MS were used for the determination of free amino acids and volatile compounds respectively. The consortium formed by K. variicola and four Lactobacillus species showed the highest production of Leu and Ile in skim milk fermentation. In addition, the production of volatile compounds, such as acetoin, ethanol, 2-nonanone, and acetic, hexanoic and octanoic acids, increased in comparison to commercial yogurt, Emmental and Gouda cheese. Also, distinctive volatiles, such as 2,3-butanediol, 4-methyl-2- hexanone and octanol, were identified. The use of K. variicola in combination with probiotic Lactobacillus species enhances the availability of Leu and Ile and the amount of distinctive volatiles during skim milk fermentation. The identified consortium increases the functional potential of fermented dairy products. © 2017 The Society for Applied Microbiology.

  5. Consumo de aminoácidos de cadeia ramificada não afeta o desempenho de endurance Branched-chain amino acids ingestion does not affect endurance performance

    Directory of Open Access Journals (Sweden)

    Marco Carlos Uchida

    2008-02-01

    Full Text Available A suplementação com aminoácidos de cadeia ramificada (BCAA é uma das manipulações dietéticas mais populares entre atletas engajados em atividades de endurance. Entretanto, o papel ergogênico destes aminoácidos ainda não está totalmente estabelecido. Portanto, o objetivo do presente trabalho foi avaliar o efeito do consumo de BCAA sobre o exercício de endurance realizado até a exaustão. A fim de provocar redução do estoque de glicogênio muscular e, por conseguinte, maximizar a utilização dos BCAA, os sujeitos (n=17 foram submetidos a uma sessão prévia de exercício (corrida realizada a 75% do VO2max por 40 min seguida por 2 tiros a 90% do VO2max por 10 min cada um. Subseqüentemente, após o consumo aleatório de BCAA (77 mg.kg-1 ou placebo, seguindo modelo duplo cego cruzado, os participantes executaram um teste para determinação da capacidade de endurance (corrida a 90% do Limiar anaeróbio até a exaustão. Ambos os experimentos, BCAA e placebo, foram separados por uma semana. Com relação ao tempo até a exaustão e a distância percorrida, nenhuma diferença foi detectada entre as condições experimentais. (Placebo: 50,1±8,9 vs BCAA: 52,4±4,5 min, respectivamente (Placebo: 8,8±1,3 vs BCAA: 9,1±0,6 km, respectivamente. Além disto, também não foi evidenciada diferença na concentração plasmática de glicose, de lactato e de amônia entre ambas condições experimentais. Em conclusão, a suplementação de BCAA não afetou o desempenho de endurance em um teste de corrida até a exaustão.Branched-chain amino acids (BCAA supplementation is one of the most popular dietary manipulations used by endurance athletes. However, the ergogenic role of these amino acids in endurance exercise is not well established yet. Therefore, the aim of this study was to evaluate the effect of BCAA supplementation upon endurance exercise performed until exhaustion. In order to induce glycogen supply reduction, and thus maximize BCAA

  6. Catabolism of leucine to branched-chain fatty acids in Staphylococcus xylosus

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Hansen, A M; Lauritsen, F R

    2004-01-01

    Staphylococcus xylosus is an important starter culture in the production of flavours from the branched-chain amino acids leucine, valine and isoleucine in fermented meat products. The sensorially most important flavour compounds are the branched-chain aldehydes and acids derived from the correspo......Staphylococcus xylosus is an important starter culture in the production of flavours from the branched-chain amino acids leucine, valine and isoleucine in fermented meat products. The sensorially most important flavour compounds are the branched-chain aldehydes and acids derived from...

  7. Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J; Junker, Anders E; Christensen, Mette

    2018-01-01

    Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action...... (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia may depend on hepatic steatosis rather than type 2 diabetes....... on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high...

  8. Post-ruminal branched-chain amino acid supplementation and intravenous lipopolysaccharide infusion alters blood metabolites, rumen fermentation, and nitrogen balance of beef steers.

    Science.gov (United States)

    Löest, C A; Gilliam, G G; Waggoner, J W; Turner, J L

    2018-04-27

    Steers exposed to an endotoxin may require additional branched-chain AA (BCAA) to support an increase in synthesis of immune proteins. This study evaluated effects of bacterial lipopolysaccharide (LPS) and BCAA supplementation on blood metabolites and N balance of 20 ruminally-cannulated steers (177 ± 4.2 kg BW). The experiment was a randomized block design, with 14-d adaptation to metabolism stalls and diet (DM fed = 1.5% BW) and 6-d collection. Treatments were a 2 × 2 factorial of LPS (0 vs 1.0 to 1.5 μg/kg BW; -LPS vs +LPS) and BCAA (0 vs 35 g/d; -BCAA vs +BCAA). The LPS in 100 mL sterile saline was infused (1 mL/min via i.v. catheter) on d 15. The BCAA in an essential AA solution were abomasally infused (900 mL/d) 3 times daily in equal portions beginning on d 7. Blood, rumen fluid, and rectal temperature were collected on d 15 at h 0, 2, 4, 8, 12, and 24 after LPS infusion. Feces and urine were collected from d 16 to 20. Rectal temperatures were greater for +LPS vs. -LPS steers at 4 h and lower at 8 h after LPS infusion (LPS h, P BCAA than -BCAA steers at 12 h after LPS infusion (BCAA × h, P BCAA, P BCAA than -BCAA steers at 0 h and 24 h after LPS infusion (BCAA × h, P ≤ 0.05). Steers receiving +LPS had lower rumen pH at 8 h, greater total VFA at 8 h, and lower rumen NH3 at 24 h after LPS infusion compared with -LPS steers (LPS × h, P ≤ 0.04). Total tract passage rates, DM, OM, NDF, ADF, and N intake, fecal N, digested N, and retained N were lower (P BCAA vs -BCAA steers. The absence of LPS × BCAA interactions (P ≥ 0.20) for N balance indicated that post-ruminal supplementation of BCAA did not alleviate the negative effects of endotoxin on N utilization by growing steers.

  9. Regulation of hepatic branched-chain alpha-keto acid dehydrogenase complex in rats fed a high-fat diet

    Science.gov (United States)

    Objective: Branched-chain alpha-keto acid dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of branched chain alpha-ketoacid (BCKA) catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal...

  10. Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes.

    Science.gov (United States)

    Wewer Albrechtsen, Nicolai J; Junker, Anders E; Christensen, Mette; Hædersdal, Sofie; Wibrand, Flemming; Lund, Allan M; Galsgaard, Katrine D; Holst, Jens J; Knop, Filip K; Vilsbøll, Tina

    2018-01-01

    Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high-performance liquid chromatography, in obese, middle-aged individuals with I) normal glucose tolerance (NGT) and NAFLD, II) T2D and NAFLD, III) T2D without liver disease, and IV) NGT and no liver disease. Elevated levels of total amino acids were observed in participants with NAFLD and NGT compared with NGT controls (1,310 ± 235 µM vs. 937 ± 281 µM, P = 0.03) and in T2D and NAFLD compared with T2D without liver disease (1,354 ± 329 µM vs. 511 ± 235 µM, P amino acids with known glucagonotropic effects (e.g., glutamine) were increased. Plasma levels of total amino acids correlated to plasma levels of glucagon also when adjusting for body mass index (BMI), glycated hemoglobin (Hb A1c ), and cholesterol levels (β = 0.013 ± 0.007, P = 0.024). Elevated plasma levels of total amino acids associate with hyperglucagonemia in NAFLD patients independently of glycemic control, BMI or cholesterol - supporting the potential importance of a "liver-α-cell axis" in which glucagon regulates hepatic amino acid metabolism. Fasting hyperglucagonemia as seen in T2D may therefore represent impaired hepatic glucagon action with increasing amino acids levels. NEW & NOTEWORTHY Hypersecretion of glucagon (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia

  11. Identification and functional characterization of the Lactococcus lactis CodY-regulated branched-chain amino acid permease BcaP (CtrA)

    NARCIS (Netherlands)

    den Hengst, CD; Groeneveld, M; Kuipers, OP; Kok, J; Hengst, Chris D. den

    Transcriptome analyses have previously revealed that a gene encoding the putative amino acid transporter CtrA (YhdG) is one of the major targets of the pleiotropic regulator CodY in Lactococcus lactis and Bacillus subtilis. The role of ctrA in L. lactis was further investigated with respect to both

  12. Bent and branched chains of nanoresonators

    Science.gov (United States)

    Melikhova, A. S.; Popov, I. Yu

    2014-10-01

    We study the spectral problem for bent and branched chains of weakly coupled conglobate resonators. At the joint points the δ-coupling is assumed. Our approach is based on the theory of self-adjoint extensions of symmetric operators and transfer matrix method. The structure of the spectrum is described. For the both cases it is proved that the Hamiltonian has negative eigenvalue for some values of the model parameters.

  13. The Ratio of Dietary Branched-Chain Amino Acids is Associated with a Lower Prevalence of Obesity in Young Northern Chinese Adults: An Internet-Based Cross-Sectional Study.

    Science.gov (United States)

    Li, Yan-Chuan; Li, Ying; Liu, Li-Yan; Chen, Yang; Zi, Tian-Qi; Du, Shan-Shan; Jiang, Yong-Shuai; Feng, Ren-Nan; Sun, Chang-Hao

    2015-11-18

    This study aims to examine the association between the ratio of dietary branched chain amino acids (BCAA) and risk of obesity among young northern Chinese adults. A total of 948 randomly recruited participants were asked to finish our internet-based dietary questionnaire for the Chinese (IDQC). Associations between dietary BCAA ratio and prevalence of overweight/obesity and abdominal obesity were analyzed. Furthermore, 90 subjects were randomly selected to explore the possible mechanism. Dietary BCAA ratio in obese participants was significantly lower than non-obese participants. We found negative correlations between the ratio of dietary BCAA and body mass index (BMI) (r = -0.197, p BCAA ratio for overweight/obesity were 0.508 (0.265-0.972) and 0.389 (0.193-0.783), respectively (all p BCAA ratio were 0.351 (0.145-0.845) and 0.376 (0.161-0.876), respectively (all p BCAA ratio was inversely associated with 2-h postprandial glucose (2 h-PG) and status of inflammation. In conclusion, a higher ratio of dietary BCAA is inversely associated with prevalence of obesity, postprandial glucose and status of inflammation in young northern Chinese adults.

  14. Two randomized controlled studies comparing the nutritional benefits of branched-chain amino acid (BCAA) granules and a BCAA-enriched nutrient mixture for patients with esophageal varices after endoscopic treatment.

    Science.gov (United States)

    Sakai, Yoshiyuki; Iwata, Yoshinori; Enomoto, Hirayuki; Saito, Masaki; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Aizawa, Nobuhiro; Ikeda, Naoto; Tanaka, Hironori; Iijima, Hiroko; Nishiguchi, Shuhei

    2015-01-01

    The usefulness of branched-chain amino acid (BCAA) granules and BCAA-enriched nutrient mixtures for patients with liver cirrhosis is often reported. However, no randomized controlled studies have investigated the usefulness of these supplements in the nutritional intervention of cirrhotic patients receiving endoscopic treatment for esophageal varices. Patients without BCAA before endoscopic treatment were divided into study 1, and those who received BCAA were divided into study 2. In study 1, 44 eligible patients were divided into a control group (n = 13), a general liquid nutrient (snack) group (n = 15), and a BCAA-enriched nutrient mixture (BCAA-EN) group (n = 16). In study 2, 48 eligible patients were divided into a BCAA group (n = 24) and a BCAA-EN group (n = 24). The nutritional status including non-protein respiratory quotient (NPRQ) levels, weight gain, and albumin were evaluated on days 0, 7, and 50. In study 1, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 as compared with the snack group. In study 2, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 and in weight levels on day 50 relative to the BCAA group, while the BCAA group showed improved serum albumin levels on day 7 compared to the BCAA-EN group. The BCAA-enriched nutrient mixture maintained NPRQ and weight in cirrhotic patients. Our findings suggest that supplements including both BCAA and a nutritional energy supplement would be beneficial for cirrhotic patients undergoing endoscopic treatment for esophageal varices.

  15. Simultaneous infusion of glutamine and branched-chain amino acids (BCAA) to septic rats does not have more favorable effect on protein synthesis in muscle, liver, and small intestine than separate infusions.

    Science.gov (United States)

    Holecek, Milan; Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek

    2006-01-01

    Glutamine and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) are used as nutrition supplements in the treatment of proteocatabolic illness. We hypothesized that simultaneous administration of BCAA and glutamine affects protein metabolism more significantly than separate administration. In the present study, we evaluated their effect on protein synthesis in skeletal muscle, liver, and jejunum of septic rats. Twenty-four hours after induction of sepsis by subcutaneous injection of turpentine, the rats were infused for 6 hours with 5 mL of 1.75% glutamine, 1.75% BCAA, 1.75% glutamine+BCAA, or saline solution. The control group consisted of intact rats infused with saline. Protein synthesis was measured at the end of infusion by a "flooding method" with [3,4,5-(3)H]phenylalanine. In turpentine-treated animals, we observed a decrease in glutamine concentration in blood plasma and skeletal muscle, a decrease in BCAA concentration in liver and jejunum, and a decrease in protein synthesis in all tissues. Glutamine or glutamine+BCAA infusion increased glutamine concentration in plasma and muscle and stimulated protein synthesis in the liver. The BCAA infusion enhanced concentrations of BCAA in plasma and tissues, but the effect of BCAA on protein synthesis was insignificant. Synergistic effect of simultaneous infusion of glutamine and BCAA on protein synthesis was not observed. We conclude that glutamine infusion to rats with septic injury may significantly improve impaired protein synthesis in the liver and that there is no synergistic effect of glutamine and BCAA infusion on protein synthesis in skeletal muscle, liver, and jejunum.

  16. A novel NMR-based assay to measure circulating concentrations of branched-chain amino acids: Elevation in subjects with type 2 diabetes mellitus and association with carotid intima media thickness.

    Science.gov (United States)

    Wolak-Dinsmore, Justyna; Gruppen, Eke G; Shalaurova, Irina; Matyus, Steven P; Grant, Russell P; Gegen, Ray; Bakker, Stephan J L; Otvos, James D; Connelly, Margery A; Dullaart, Robin P F

    2018-04-01

    Plasma branched-chain amino acid (BCAA) levels, measured on nuclear magnetic resonance (NMR) metabolomics research platforms or by mass spectrometry, have been shown to be associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We developed a new test for quantification of BCAA on a clinical NMR analyzer and used this test to determine the clinical correlates of BCAA in 2 independent cohorts. The performance of the NMR-based BCAA assay was evaluated. A method comparison study was performed with mass spectrometry (LC-MS/MS). Plasma BCAA were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1209; 376 T2DM subjects) and in a Groningen cohort (n = 123; 67 T2DM subjects). In addition, carotid intima media thickness (cIMT) was measured successfully in 119 subjects from the Groningen cohort. NMR-based BCAA assay results were linear over a range of concentrations. Coefficients of variation for inter- and intra-assay precision ranged from 1.8-6.0, 1.7-5.4, 4.4-9.1, and 8.8-21.3%, for total BCAA, valine, leucine, and isoleucine, respectively. BCAA quantified from the same samples using NMR and LC-MS/MS were highly correlated (R 2  = 0.97, 0.95 and 0.90 for valine, leucine and isoleucine). In both cohorts total and individual BCAA were elevated in T2DM (P = 0.01 to ≤0.001). Moreover, cIMT was associated with BCAA independent of age, sex, T2DM and metabolic syndrome (MetS) categorization or alternatively of individual MetS components. BCAA levels, measured by NMR in the clinical laboratory, are elevated in T2DM and may be associated with cIMT, a proxy of subclinical atherosclerosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Whey protein supplementation does not alter plasma branched-chained amino acid profiles but results in unique metabolomics patterns in obese women enrolled in an 8-week weight loss trial.

    Science.gov (United States)

    Piccolo, Brian D; Comerford, Kevin B; Karakas, Sidika E; Knotts, Trina A; Fiehn, Oliver; Adams, Sean H

    2015-04-01

    It has been suggested that perturbations in branched-chain amino acid (BCAA) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs. Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism, but there is limited evidence in humans. We hypothesize that a diet rich in BCAAs will increase BCAA catabolism, which will manifest in a reduction of fasting plasma BCAA concentrations. The metabolome of 27 obese women with metabolic syndrome before and after weight loss was investigated to identify changes in BCAA metabolism using GC-time-of-flight mass spectrometry. Subjects were enrolled in an 8-wk weight-loss study including either a 20-g/d whey (whey group, n = 16) or gelatin (gelatin group, n = 11) protein supplement. When matched for total protein by weight, whey protein has 3 times the amount of BCAAs compared with gelatin protein. Postintervention plasma abundances of Ile (gelatin group: 637 ± 18, quantifier ion peak height ÷ 100; whey group: 744 ± 65), Leu (gelatin group: 1210 ± 33; whey group: 1380 ± 79), and Val (gelatin group: 2080 ± 59; whey group: 2510 ± 230) did not differ between treatment groups. BCAAs were significantly correlated with homeostasis model assessment of insulin resistance at baseline (r = 0.52, 0.43, and 0.49 for Leu, Ile, and Val, respectively; all, P BCAA metabolism is, at best, only modestly affected at a whey protein supplementation dose of 20 g/d. Furthermore, the loss of an association between postintervention BCAA and homeostasis model assessment suggests that factors associated with calorie restriction or protein intake affect how plasma BCAAs relate to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00739479. © 2015 American Society for Nutrition.

  18. Effects of Supplementation of Branched-Chain Amino Acids to Reduced-Protein Diet on Skeletal Muscle Protein Synthesis and Degradation in the Fed and Fasted States in a Piglet Model

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng

    2016-12-01

    Full Text Available Supplementation of branched-chain amino acids (BCAA has been demonstrated to promote skeletal muscle mass gain, but the mechanisms underlying this observation are still unknown. Since the regulation of muscle mass depends on a dynamic equilibrium (fasted losses–fed gains in protein turnover, the aim of this study was to investigate the effects of BCAA supplementation on muscle protein synthesis and degradation in fed/fasted states and the related mechanisms. Fourteen 26- (Experiment 1 and 28-day-old (Experiment 2 piglets were fed reduced-protein diets without or with supplemental BCAA. After a four-week acclimation period, skeletal muscle mass and components of anabolic and catabolic signaling in muscle samples after overnight fasting were determined in Experiment 1. Pigs in Experiment 2 were implanted with carotid arterial, jugular venous, femoral arterial and venous catheters, and fed once hourly along with the intravenous infusion of NaH13CO3 for 2 h, followed by a 6-h infusion of [1-13C]leucine. Muscle leucine kinetics were measured using arteriovenous difference technique. The mass of most muscles was increased by BCAA supplementation. During feeding, BCAA supplementation increased leucine uptake, protein synthesis, protein degradation and net transamination. The greater increase in protein synthesis than in protein degradation resulted in elevated protein deposition. Protein synthesis was strongly and positively correlated with the intramuscular net production of α-ketoisocaproate (KIC and protein degradation. Moreover, BCAA supplementation enhanced the fasted-state phosphorylation of protein translation initiation factors and inhibited the protein-degradation signaling of ubiquitin-proteasome and autophagy-lysosome systems. In conclusion, supplementation of BCAA to reduced-protein diet increases fed-state protein synthesis and inhibits fasted-state protein degradation, both of which could contribute to the elevation of skeletal muscle

  19. The Ratio of Dietary Branched-Chain Amino Acids is Associated with a Lower Prevalence of Obesity in Young Northern Chinese Adults: An Internet-Based Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Yan-Chuan Li

    2015-11-01

    Full Text Available This study aims to examine the association between the ratio of dietary branched chain amino acids (BCAA and risk of obesity among young northern Chinese adults. A total of 948 randomly recruited participants were asked to finish our internet-based dietary questionnaire for the Chinese (IDQC. Associations between dietary BCAA ratio and prevalence of overweight/obesity and abdominal obesity were analyzed. Furthermore, 90 subjects were randomly selected to explore the possible mechanism. Dietary BCAA ratio in obese participants was significantly lower than non-obese participants. We found negative correlations between the ratio of dietary BCAA and body mass index (BMI (r = −0.197, p < 0.001 or waist circumference (r = −0.187, p < 0.001. Compared with those in the first quartile, the multivariable-adjusted OR (95% CI of the 3rd and 4th quartiles of dietary BCAA ratio for overweight/obesity were 0.508 (0.265–0.972 and 0.389 (0.193–0.783, respectively (all p < 0.05. After stratification by gender, the significance still existed in the 3rd and 4th quartile in males and the 4th quartile in females. For abdominal obesity, the multivariable-adjusted OR (95% CI of the 3rd and 4th quartile of dietary BCAA ratio were 0.351 (0.145–0.845 and 0.376 (0.161–0.876, respectively (all p < 0.05. This significance was stronger in males. Further studies indicated that dietary BCAA ratio was inversely associated with 2-h postprandial glucose (2 h-PG and status of inflammation. In conclusion, a higher ratio of dietary BCAA is inversely associated with prevalence of obesity, postprandial glucose and status of inflammation in young northern Chinese adults.

  20. Cluster analysis of indicators of liver functional and preoperative low branched-chain amino acid tyrosine ration indicate a high risk of early recurrence in analysis of 165 hepatocellular carcinoma patients after initial hepatectomy.

    Science.gov (United States)

    Nakamura, Yukio; Mizuguchi, Toru; Kawamoto, Masaki; Meguro, Makoto; Harada, Kohei; Ota, Shigenori; Hirata, Koichi

    2011-08-01

    Cluster analysis is used for dividing many prognostic indicators, including liver function, tumor progression, and operative variables, into specific clusters. The albumin (ALB), hepatocyte growth factor (HGF), and branched chain amino-acid to tyrosine ratio (BTR) may represent the severity of liver disease and function of the hepatic reserve. We developed the ALB-BTR and HGF-BTR classifications depending on each level to find specific unique subgroups. Our aim was to identify specific subgroups destined for favorable and poor prognoses after initial hepatectomy. Between 2002 and 2008, 165 patients were analyzed retrospectively. Liver function indicators, including BTR, tumor-related factors, and operative variables, were evaluated by cluster analysis with Ward's criterion. The ALB-BTR classification was divided into 4 groups depending on ALB (cutoff value, 4.0 g/dL) and BTR (cutoff value, 6.0). The HGF-BTR classification was also divided into 4 groups depending on HGF (cutoff value, 0.35 ng/mL) and BTR (cutoff value, 6.0). The prognoses of the subgroups were compared by the log-rank test. Cluster analysis divided multiple indicators into 5 different clusters. In each cluster, we further analyzed subgroups using the ALB-BTR and HGF-BTR classification. Mean recurrence-free survival times in ALB-GI (19.1 ± 2.4 months) and HGF-GIII (29.4 ± 3.8 months) were less than their mean overall survival times. Cluster analysis is useful to find similar and different indicators. Even though liver function was well preserved, low BTR could identify early recurrence in hepatocellular carcinoma patients after resection. Copyright © 2011 Mosby, Inc. All rights reserved.

  1. Side Chain Cyclized Aromatic Amino Acids

    DEFF Research Database (Denmark)

    Van der Poorten, Olivier; Knuhtsen, Astrid; Sejer Pedersen, Daniel

    2016-01-01

    Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute...... the peptide pharmacophore is equally important. Control of χ-space utilizes conformationally constrained amino acids that favor, disfavor, or exclude the gauche (-), the gauche (+), or the trans conformation. In this review we focus on cyclic aromatic amino acids in which the side chain is connected...... to the peptide backbone to provide control of χ(1)- and χ(2)-space. The manifold applications for cyclized analogues of the aromatic amino acids Phe, Tyr, Trp, and His within peptide medicinal chemistry are showcased herein with examples of enzyme inhibitors and ligands for G protein-coupled receptors....

  2. Efeito dos aminoácidos de cadeia ramificada no músculo imobilizado e no músculo desnervado = Effect of branched - chain amino acids on immobilized skeletal muscle and denervated muscle

    Directory of Open Access Journals (Sweden)

    Pezolato, Vitor Alexandre

    2014-01-01

    Full Text Available Objetivo: Este trabalho teve como objetivo avaliar histologicamente o músculo sóleo imobilizado e desnervado de ratos suplementados com aminoácidos de cadeia ramificada. Materiais e Métodos: Para a realização da pesquisa foram utilizados 30 ratos navergicus albinus machos, variedade Wistar, com 3 a 4 meses de vida, divididos em 6 grupos (n=5 e denominados: controle (C, desnervado 7 dias (D, imobilizado 7 dias (I, suplementado com aminoácidos de cadeia ramificada 7 dias (BCAA, desnervado suplementado com aminoácidos de cadeia ramificada (D+BCAA e imobilizado suplementado com aminoácidos de cadeia ramificada (I+BCAA. Os animais desnervados passaram pelo seccionamento do nervo ciático (1 cm. O s animais dos grupos imobilizados receberam uma órtese de resina acrílica acoplada na pata posterior promovendo a imobilização. Após a fase experimental os animais foram eutanasiados e os músculos foram analisados histologicamente. O teste de Shapiro - Wilk avaliou a normalidade dos dados, seguido da análise de variância e, posteriormente, Tukey - Kramer com nível de significância menor de 5%. Resultados: A suplementação aumentou a área de secçã o transversa da fibra muscular em 74,94% no grupo I+BCAA e 90,37% no grupo D+BCAA em relação aos grupos I e D, respectivamente. Houve aumento de 97,21% na densidade de área de tecido conjuntivo no grupo BCAA em relação ao grupo C, porém a suplementação pro moveu redução de 34,44% no grupo D+BCAA em relação ao grupo D, no entanto, não houve diferença significativa entre os grupos I+BCAA e I. Conclusão: Observa-se que a utilização dos aminoácidos de cadeia ramificada pode diminuir a atrofia provocada pelo desuso muscular, tanto na condição de desnervação quanto na condição de imobilização

  3. Characterization of Potential Antimicrobial Targets in Bacillus spp. II. Branched-Chain Aminotransferase and Methionine Regeneration in B. cereus and B. anthracis

    National Research Council Canada - National Science Library

    Berger, B

    2002-01-01

    .... Four putative family III aminotransferases, two with homology to branched-chain amino acid aminotransferases and two with homology to D- amino acid aminotransferases, were cloned from B. cereus...

  4. Relationship between branched-chain amino acid to tyrosine ratio (BTR) and porta-systemic shunt in the child-pugh grade a cirrhosis determined by per-rectal portal scintigraphy

    International Nuclear Information System (INIS)

    Daiki Habu; Shuhei Nishiguchi; Shinji Nakatani; Etsushi Kawamurab; Hirotaka Ishizub; Chulyoo Lee; Satoko Ohfujia; Wakaba Fukushimaa; Takashi Tanakaa; Kenji Toriib; Joji Kawabeb; Toji Kawamurab; Susumu Shiomib

    2004-01-01

    Purpose: It has been reported that the branched-chain amino acid (BCAA) to aromatic amino acid (AAA) ratio (Fisher $B!G (Bs ratio) is an important prognostic factor in cirrhosis. The clinical significance of the ratio of serum molar concentration of BCAA to that of tyrosine (BCAA to tyrosine ratio; BTR) resembles that of Fisher $B!G (Bs ratio, In Japan, because determination of BTR simpler and cheaper than that of Fisher $B!G (Bs ratio, BTR is now widely used for assessment of abnormality of amino acid metabolism in cirrhosis. In this study, we examined the difference between early cirrhotic patients with lower BTR and higher BTR in portal circulation using per-rectal portal scintigraphy with technetium-99m ( 99m Tc) pertechnetate. Patients and Methods: Forty patients with Child-Pugh grade A cirrhosis and serum albumin level between 3.5 g/dl and 3.9 g/dl were enrolled in this study. Sixteen patients were infected with HBV and 24 with HCV. At entry, we measured the ratio of serum molar concentration of BCAA to that of tyrosine (BTR). BTR was measured by an enzymatic method (Ono Pharmaceutical Co., Ltd., Osaka, Japan). Thirteen patients had BTR 4.0. At the same time, we measured serum albumin, platelets, total bilirubin, prothrombin test, retention of indocyanine green in plasma after 15 minutes (ICGR-15) and NH3. To evaluate the portal circulation, all patients underwent per-rectal portal scintigraphy. A 370 MBq portion of 99m Tc-pertechnetate (2 ml) was first given per rectum through a polyethylene tube, followed by 15 ml of air. Then time-activity curves for the heart and liver areas were obtained every 4 sec. At the enol of the 5 min-examinations, the 5-min summed image displayed in color was recorded. To evaluate the extent of porta-systemic shunt by shunt index (SI), we calculated the ratio of counts for the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. Results: Shunt index obtained

  5. Developmental changes in rat liver branched-chain 2-oxo acid dehydrogenase.

    OpenAIRE

    May, E E; May, M E; Aftring, R P; Buse, M G

    1982-01-01

    Branched-chain 2-oxo acid dehydrogenase catalyses the first irreversible step in the degradation of the branched-chain amino acids leucine, isoleucine and valine. With specifically labelled 4-methyl-2-oxo[1-14C]pentanoate as substrate, the enzyme's activity was measured in rat liver homogenates. Activity (per g wet wL of liver or per mg of protein) increased most rapidly during the perinatal period (2 days before to 1 day after birth), reaching approximately adult values by the time of weanin...

  6. Simple model of inhibition of chain-branching combustion processes

    Science.gov (United States)

    Babushok, Valeri I.; Gubernov, Vladimir V.; Minaev, Sergei S.; Miroshnichenko, Taisia P.

    2017-11-01

    A simple kinetic model has been suggested to describe the inhibition and extinction of flame propagation in reaction systems with chain-branching reactions typical for hydrocarbon systems. The model is based on the generalised model of the combustion process with chain-branching reaction combined with the one-stage reaction describing the thermal mode of flame propagation with the addition of inhibition reaction steps. Inhibitor addition suppresses the radical overshoot in flame and leads to the change of reaction mode from the chain-branching reaction to a thermal mode of flame propagation. With the increase of inhibitor the transition of chain-branching mode of reaction to the reaction with straight-chains (non-branching chain reaction) is observed. The inhibition part of the model includes a block of three reactions to describe the influence of the inhibitor. The heat losses are incorporated into the model via Newton cooling. The flame extinction is the result of the decreased heat release of inhibited reaction processes and the suppression of radical overshoot with the further decrease of the reaction rate due to the temperature decrease and mixture dilution. A comparison of the results of modelling laminar premixed methane/air flames inhibited by potassium bicarbonate (gas phase model, detailed kinetic model) with the results obtained using the suggested simple model is presented. The calculations with the detailed kinetic model demonstrate the following modes of combustion process: (1) flame propagation with chain-branching reaction (with radical overshoot, inhibitor addition decreases the radical overshoot down to the equilibrium level); (2) saturation of chemical influence of inhibitor, and (3) transition to thermal mode of flame propagation (non-branching chain mode of reaction). The suggested simple kinetic model qualitatively reproduces the modes of flame propagation with the addition of the inhibitor observed using detailed kinetic models.

  7. Studies on the production of branched-chain alcohols in engineered Ralstonia eutropha

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jingnan [Massachusetts Institute of Technology, Cambridge, MA (United States). Dept. of Chemistry; Brigham, Christopher J.; Gai, Claudia S. [Massachusetts Institute of Technology, Cambridge, MA (United States). Dept. of Biology; Sinskey, Anthony J. [Massachusetts Institute of Technology, Cambridge, MA (United States). Dept. of Biology; Massachusetts Institute of Technology, Cambridge, MA (United States). Div. of Health Sciences and Technology; Massachusetts Institute of Technology, Cambridge, MA (United States). Engineering Systems Div.

    2012-10-15

    Wild-type Ralstonia eutropha H16 produces polyhydroxybutyrate (PHB) as an intracellular carbon storage material during nutrient stress in the presence of excess carbon. In this study, the excess carbon was redirected in engineered strains from PHB storage to the production of isobutanol and 3-methyl-1-butanol (branched-chain higher alcohols). These branched-chain higher alcohols can directly substitute for fossil-based fuels and be employed within the current infrastructure. Various mutant strains of R. eutropha with isobutyraldehyde dehydrogenase activity, in combination with the overexpression of plasmid-borne, native branched-chain amino acid biosynthesis pathway genes and the overexpression of heterologous ketoisovalerate decarboxylase gene, were employed for the biosynthesis of isobutanol and 3-methyl-1-butanol. Production of these branched-chain alcohols was initiated during nitrogen or phosphorus limitation in the engineered R. eutropha. One mutant strain not only produced over 180 mg/L branched-chain alcohols in flask culture, but also was significantly more tolerant of isobutanol toxicity than wild-type R. eutropha. After the elimination of genes encoding three potential carbon sinks (ilvE, bkdAB, and aceE), the production titer improved to 270 mg/L isobutanol and 40 mg/L 3-methyl-1-butanol. Semicontinuous flask cultivation was utilized to minimize the toxicity caused by isobutanol while supplying cells with sufficient nutrients. Under this semicontinuous flask cultivation, the R. eutropha mutant grew and produced more than 14 g/L branched-chain alcohols over the duration of 50 days. These results demonstrate that R. eutropha carbon flux can be redirected from PHB to branched-chain alcohols and that engineered R. eutropha can be cultivated over prolonged periods of time for product biosynthesis. (orig.)

  8. Kinetics of thermophilic, anaerobic oxidation of straight and branched chain butyrate and valerate

    DEFF Research Database (Denmark)

    Batstone, Damien J.; Pind, Peter Frode; Angelidaki, Irini

    2003-01-01

    The degradation kinetics of normal and branched chain butyrate and valerate are important in protein-fed anaerobic systems, as a number of amino acids degrade to these organic acids. Including activated and primary wastewater sludge digesters, the majority of full-scale systems digest feeds...... is also addressed, extending previous pure-culture and batch studies. A previously published mathematical model was modified to allow competitive uptake of i-valerate, and used to model a thermophilic manure digester operated over 180 days. The digester was periodically pulsed with straight and branched...

  9. On the contraction factors of long-chain branched macromolecules

    Czech Academy of Sciences Publication Activity Database

    Kratochvíl, Pavel; Netopilík, Miloš

    2014-01-01

    Roč. 51, February (2014), s. 177-181 ISSN 0014-3057 R&D Projects: GA ČR GCP205/11/J043 Institutional support: RVO:61389013 Keywords : long- chain branching * contraction factor * radius of gyration Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.005, year: 2014

  10. Dissociation of branched-chain alpha-keto acid dehydrogenase kinase (BDK) from branched-chain alpha-keto acid dehydrogenase complex (BCKDC) by BDK inhibitors.

    Science.gov (United States)

    Murakami, Taro; Matsuo, Masayuki; Shimizu, Ayako; Shimomura, Yoshiharu

    2005-02-01

    Branched-chain alpha-keto acid dehydrogenase kinase (BDK) phosphorylates and inactivates the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), which is the rate-limiting enzyme in the branched-chain amino acid catabolism. BDK has been believed to be bound to the BCKDC. However, recent our studies demonstrated that protein-protein interaction between BDK and BCKDC is one of the factors to regulate BDK activity. Furthermore, only the bound form of BDK appears to have its activity. In the present study, we examined effects of BDK inhibitors on the amount of BDK bound to the BCKDC using rat liver extracts. The bound form of BDK in the extracts of liver from low protein diet-fed rats was measured by an immunoprecipitation pull down assay with or without BDK inhibitors. Among the BDK inhibitors. alpha-ketoisocaproate, alpha-chloroisocaproate, and a-ketoisovalerate released the BDK from the complex. Furthermore, the releasing effect of these inhibitors on the BDK appeared to depend on their inhibition constants. On the other hand, clofibric acid and thiamine pyrophosphate had no effect on the protein-protein interaction between two enzymes. These results suggest that the dissociation of the BDK from the BCKDC is one of the mechanisms responsible for the action of some inhibitors to BDK.

  11. Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

    Science.gov (United States)

    Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

    2016-02-05

    Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Additional chain-branching pathways in the low-temperature oxidation of branched alkanes

    KAUST Repository

    Wang, Zhandong

    2015-12-31

    Chain-branching reactions represent a general motif in chemistry, encountered in atmospheric chemistry, combustion, polymerization, and photochemistry; the nature and amount of radicals generated by chain-branching are decisive for the reaction progress, its energy signature, and the time towards its completion. In this study, experimental evidence for two new types of chain-branching reactions is presented, based upon detection of highly oxidized multifunctional molecules (HOM) formed during the gas-phase low-temperature oxidation of a branched alkane under conditions relevant to combustion. The oxidation of 2,5-dimethylhexane (DMH) in a jet-stirred reactor (JSR) was studied using synchrotron vacuum ultra-violet photoionization molecular beam mass spectrometry (SVUV-PI-MBMS). Specifically, species with four and five oxygen atoms were probed, having molecular formulas of C8H14O4 (e.g., diketo-hydroperoxide/keto-hydroperoxy cyclic ether) and C8H16O5 (e.g., keto-dihydroperoxide/dihydroperoxy cyclic ether), respectively. The formation of C8H16O5 species involves alternative isomerization of OOQOOH radicals via intramolecular H-atom migration, followed by third O2 addition, intramolecular isomerization, and OH release; C8H14O4 species are proposed to result from subsequent reactions of C8H16O5 species. The mechanistic pathways involving these species are related to those proposed as a source of low-volatility highly oxygenated species in Earth\\'s troposphere. At the higher temperatures relevant to auto-ignition, they can result in a net increase of hydroxyl radical production, so these are additional radical chain-branching pathways for ignition. The results presented herein extend the conceptual basis of reaction mechanisms used to predict the reaction behavior of ignition, and have implications on atmospheric gas-phase chemistry and the oxidative stability of organic substances. © 2015 The Combustion Institute.

  13. Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Joanne M Kingsbury

    2015-12-01

    Full Text Available The conserved target of rapamycin complex 1 (TORC1 integrates nutrient signals to orchestrate cell growth and proliferation. Leucine availability is conveyed to control TORC1 activity via the leu-tRNA synthetase/EGOC-GTPase module in yeast and mammals, but the mechanisms sensing leucine remain only partially understood. We show here that both leucine and its α-ketoacid metabolite, α-ketoisocaproate, effectively activate the yeast TORC1 kinase via both EGOC GTPase-dependent and -independent mechanisms. Leucine and α-ketoisocaproate are interconverted by ubiquitous branched-chain aminotransferases (BCAT, which in yeast are represented by the mitochondrial and cytosolic enzymes Bat1 and Bat2, respectively. BCAT yeast mutants exhibit severely compromised TORC1 activity, which is partially restored by expression of Bat1 active site mutants, implicating both catalytic and structural roles of BCATs in TORC1 control. We find that Bat1 interacts with branched-chain amino acid metabolic enzymes and, in a leucine-dependent fashion, with the tricarboxylic acid (TCA-cycle enzyme aconitase. BCAT mutation perturbed TCA-cycle intermediate levels, consistent with a TCA-cycle block, and resulted in low ATP levels, activation of AMPK, and TORC1 inhibition. We propose the biosynthetic capacity of BCAT and its role in forming multicomplex metabolons connecting branched-chain amino acids and TCA-cycle metabolism governs TCA-cycle flux to activate TORC1 signaling. Because mammalian mitochondrial BCAT is known to form a supramolecular branched-chain α-keto acid dehydrogenase enzyme complex that links leucine metabolism to the TCA-cycle, these findings establish a precedent for understanding TORC1 signaling in mammals.

  14. Nucleotide sequence of a cDNA for branched chain acyltransferase with analysis of the deduced protein structure

    International Nuclear Information System (INIS)

    Hummel, K.B.; Litwer, S.; Bradford, A.P.; Aitken, A.; Danner, D.J.; Yeaman, S.J.

    1988-01-01

    Nucleotide sequence was determined for a 1.6-kilobase human cDNA putative for the branched chain acyltransferase protein of the branched chain α-ketoacid dehydrogenase complex. Translation of the sequence reveals an open reading frame encoding a 315-amino acid protein of molecular weight 35,759 followed by 560 bases of 3'-untranslated sequence. Three repeats of the polyadenylation signal hexamer ATTAAA are present prior to the polyadenylate tail. Within the open reading frame is a 10-amino acid fragment which matches exactly the amino acid sequence around the lipoate-lysine residue in bovine kidney branched chain acyltransferase, thus confirming the identity of the cDNA. Analysis of the deduced protein structure for the human branched chain acyltransferase revealed an organization into domains similar to that reported for the acyltransferase proteins of the pyruvate and α-ketoglutarate dehydrogenase complexes. This similarity in organization suggests that a more detailed analysis of the proteins will be required to explain the individual substrate and multienzyme complex specificity shown by these acyltransferases

  15. Biological Functions of ilvC in Branched-Chain Fatty Acid Synthesis and Diffusible Signal Factor Family Production in Xanthomonas campestris

    OpenAIRE

    Kai-Huai Li; Yong-Hong Yu; Hui-Juan Dong; Wen-Bin Zhang; Jin-Cheng Ma; Hai-Hong Wang

    2017-01-01

    In bacteria, the metabolism of branched-chain amino acids (BCAAs) is tightly associated with branched-chain fatty acids (BCFAs) synthetic pathways. Although previous studies have reported on BCFAs biosynthesis, more detailed associations between BCAAs metabolism and BCFAs biosynthesis remain to be addressed. In this study, we deleted the ilvC gene, which encodes ketol-acid reductoisomerase in the BCAAs synthetic pathway, from the Xanthomonas campestris pv. campestris (Xcc) genome. We characte...

  16. Topological analysis of long-chain branching patterns in polyolefins.

    Science.gov (United States)

    Bonchev, D; Markel, E; Dekmezian, A

    2001-01-01

    Patterns in molecular topology and complexity for long-chain branching are quantitatively described. The Wiener number, the topological complexity index, and a new index of 3-starness are used to quantify polymer structure. General formulas for these indices were derived for the cases of 3-arm star, H-shaped, and B-arm comb polymers. The factors affecting complexity in monodisperse polymer systems are ranked as follows: number of arms > arm length > arm central position approximately equal to arm clustering > total molecular weight approximately equal to backbone molecular weight. Topological indices change rapidly and then plateau as the molecular weight of branches on a polyolefin backbone increases from 0 to 5 kD. Complexity calculations relate 2-arm or 3-arm comb structures to the corresponding 3-arm stars of equivalent complexity but much higher molecular weight. In a subsequent paper, we report the application of topological analysis for developing structure/property relationships for monodisperse polymers. While the focus of the present work is on the description of monodisperse, well-defined architectures, the methods may be extended to the description of polydisperse systems.

  17. Improved zeolite regeneration processes for preparing saturated branched-chain fatty acids

    Science.gov (United States)

    Ferrierite zeolite solid is an excellent catalyst for the skeletal isomerization of unsaturated linear-chain fatty acids (i.e., oleic acid) to unsaturated branched-chain fatty acids (i.e., iso-oleic acid) follow by hydrogenation to give saturated branched-chain fatty acids (i.e., isostearic acid). ...

  18. Dietary branched-chain amino acid (BCAA) and tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Chan, W.; Baron, L.; Baron, P.; White, F.; Banks, W.L. Jr.

    1986-03-05

    The effects of high dietary BCAA on tumor growth was examined in adult male Fischer 344 rats inoculated with 10/sup 6/ viable MCA fibrosarcoma cells. Ten days after tumor inoculation, when tumors were of palpable size, rats were divided into two groups at random. The experimental(E) group was fed the AIN-76 diet supplemented with 4X the BCAA content of diet casein and the control(C) group was fed the AIN-76 made isonitrogenous with the E diet by glutamic acid supplementation. Five rats from each group were killed at days 0,3,6, and 9. Rats were injected with /sup 14/C-Tyrosine and /sup 3/H-Thymidine i.p. (2 and 4 uCi/100g BW, respectively) an hour before they were killed. The incorporation of /sup 14/C and /sup 3/H into the acid insoluble fraction of the tumor tissues samples were measured. Single cell suspension of tumor were prepared for cell cycle kinetics analysis using a Coulter EPICS IV flow microflorometer. The percentage of normal and hyperdiploid cells were analyzed. Results showed that both tumor size and weight were doubled at each time point the rats were killed. At day 0, the /sup 3/H and /sup 14/C incorporation were 32 +/- 10dpm and 27 +/- 4dpm/mg tumor, respectively. The /sup 3/H incorporation dropped in both diet groups at days 6 and 9 but the /sup 14/C incorporation showed a decrease only at day 9. These changes were statistically significant, P>0.05. No difference in the tumor growth parameters used in this study can be attributed to the high dietary BCAA.

  19. Dietary branched-chain amino acid (BCAA) and tumor growth

    International Nuclear Information System (INIS)

    Chan, W.; Baron, L.; Baron, P.; White, F.; Banks, W.L. Jr.

    1986-01-01

    The effects of high dietary BCAA on tumor growth was examined in adult male Fischer 344 rats inoculated with 10 6 viable MCA fibrosarcoma cells. Ten days after tumor inoculation, when tumors were of palpable size, rats were divided into two groups at random. The experimental(E) group was fed the AIN-76 diet supplemented with 4X the BCAA content of diet casein and the control(C) group was fed the AIN-76 made isonitrogenous with the E diet by glutamic acid supplementation. Five rats from each group were killed at days 0,3,6, and 9. Rats were injected with 14 C-Tyrosine and 3 H-Thymidine i.p. (2 and 4 uCi/100g BW, respectively) an hour before they were killed. The incorporation of 14 C and 3 H into the acid insoluble fraction of the tumor tissues samples were measured. Single cell suspension of tumor were prepared for cell cycle kinetics analysis using a Coulter EPICS IV flow microflorometer. The percentage of normal and hyperdiploid cells were analyzed. Results showed that both tumor size and weight were doubled at each time point the rats were killed. At day 0, the 3 H and 14 C incorporation were 32 +/- 10dpm and 27 +/- 4dpm/mg tumor, respectively. The 3 H incorporation dropped in both diet groups at days 6 and 9 but the 14 C incorporation showed a decrease only at day 9. These changes were statistically significant, P>0.05. No difference in the tumor growth parameters used in this study can be attributed to the high dietary BCAA

  20. The branched-chain amino acid requerement in neonates

    NARCIS (Netherlands)

    F. Maingay-de Groof (Femke)

    2012-01-01

    textabstractGrowth during the earliest stages of life is an important determinant of an individual’s later health and risk of chronic disease. Substantial evidence shows that growth in the first 2 years of life, especially high early weight gain, is associated with adverse health outcomes later in

  1. Properties of Confined Star-Branched and Linear Chains. A Monte Carlo Simulation Study

    International Nuclear Information System (INIS)

    Romiszowski, P.; Sikorski, A.

    2004-01-01

    A model of linear and star-branched polymer chains confined between two parallel and impenetrable surfaces was built. The polymer chains were restricted to a simple cubic lattice. Two macromolecular architectures of the chain: linear and star branched (consisted of f = 3 branches of equal length) were studied. The excluded volume was the only potential introduced into the model (the athermal system). Monte Carlo simulations were carried out using a sampling algorithm based on chain's local changes of conformation. The simulations were carried out at different confinement conditions: from light to high chain's compression. The scaling of chain's size with the chain length was studied and discussed. The influence of the confinement and the macromolecular architecture on the shape of a chain was studied. The differences in the shape of linear and star-branched chains were pointed out. (author)

  2. Strain hardening in startup shear of long-chain branched polymer solutions.

    Science.gov (United States)

    Liu, Gengxin; Cheng, Shiwang; Lee, Hyojoon; Ma, Hongwei; Xu, Hongde; Chang, Taihyun; Quirk, Roderic P; Wang, Shi-Qing

    2013-08-09

    We show for the first time that entangled polymeric liquids containing long-chain branching can exhibit strain hardening upon startup shear. As the significant long-chain branching impedes chain disentanglement, Gaussian coils between entanglements can deform to reach the finite extensibility limit where the intrachain retraction force exceeds the value expected from the usual conformational entropy loss evaluated based on Gaussian chain statistics. The phenomenon is expected to lead to further theoretical understanding.

  3. Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase during exercise in man

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; MacLean, D A; Saltin, B

    1996-01-01

    1. Exercise leads to activation (dephosphorylation) of the branched-chain alpha-keto acid dehydrogenase (BCKADH). Here we investigate the effect of low pre-exercise muscle glycogen content and of branched-chain amino acid (BCAA) ingestion on the activity of BCKADH at rest and after 90 min of one......-leg knee-extensor exercise at 65% maximal one-leg power output in five subjects. 2. Pre-exercise BCAA ingestion (308 mg BCAAs (kg body wt)-1) caused an increased muscle BCAA uptake, a higher intramuscular BCAA concentration and activation of BCKADH both at rest (9 +/- 1 versus 25 +/- 5% for the control...... and BCAA test, respectively) and after exercise (27 +/- 4 versus 54 +/- 7%). 3. At rest the percentage active BCKADH was not different, 6 +/- 2% versus 5 +/- 1%, in the normal and low glycogen content leg (392 +/- 21 and 147 +/- 34 mumol glycosyl units (g dry muscle)-1, respectively). The post...

  4. Converging from branching to linear metrics on Markov chains

    DEFF Research Database (Denmark)

    Bacci, Giorgio; Bacci, Giovanni; Larsen, Kim G.

    2017-01-01

    -approximant is computable in polynomial time in the size of the MC. The upper-approximants are bisimilarity-like pseudometrics (hence, branching-time distances) that converge point-wise to the linear-time metrics. This convergence is interesting in itself, because it reveals a nontrivial relation between branching...

  5. Converging from Branching to Linear Metrics on Markov Chains

    DEFF Research Database (Denmark)

    Bacci, Giorgio; Bacci, Giovanni; Larsen, Kim Guldstrand

    2015-01-01

    time in the size of the MC. The upper-approximants are Kantorovich-like pseudometrics, i.e. branching-time distances, that converge point-wise to the linear-time metrics. This convergence is interesting in itself, since it reveals a nontrivial relation between branching and linear-time metric...

  6. Effect of short-chain branching on interfacial polymer structure and dynamics under shear flow.

    Science.gov (United States)

    Jeong, Sohdam; Kim, Jun Mo; Cho, Soowon; Baig, Chunggi

    2017-11-22

    We present a detailed analysis on the effect of short-chain branches on the structure and dynamics of interfacial chains using atomistic nonequilibrium molecular dynamics simulations of confined polyethylene melts in a wide range of shear rates. The intrinsically fast random motions of the short branches constantly disturb the overall chain conformation, leading to a more compact and less deformed chain structure of the short-chain branched (SCB) polymer against the imposed flow field in comparison with the corresponding linear polymer. Moreover, such highly mobile short branches along the backbone of the SCB polymer lead to relatively weaker out-of-plane wagging dynamics of interfacial chains, with highly curvy backbone structures in the intermediate flow regime. In conjunction with the contribution of short branches (as opposed to that of the backbone) to the total interfacial friction between the chains and the wall, the SCB polymer shows a nearly constant behavior in the degree of slip (d s ) with respect to shear rate in the weak-to-intermediate flow regimes. On the contrary, in the strong flow regime where irregular chain rotation and tumbling dynamics occur via intensive dynamical collisions between interfacial chains and the wall, an enhancement effect on the chain detachment from the wall, caused by short branches, leads to a steeper increase in d s for the SCB polymer than for the linear polymer. Remarkably, the SCB chains at the interface exhibit two distinct types of rolling mechanisms along the backbone, with a half-dumbbell mesoscopic structure at strong flow fields, in addition to the typical hairpin-like tumbling behavior displayed by the linear chains.

  7. [Odd- and branched-chain fatty acids in milk fat--characteristic and health properties].

    Science.gov (United States)

    Adamska, Agata; Rutkowska, Jarosława

    2014-08-22

    This review analyzes the current state of knowledge on odd- and branched-chain fatty acids present in milk fat. Special attention is devoted to the characteristic, synthesis in ruminants, factors affecting their content in milk fat and pro-health properties of these compounds. The group of odd- and branched-chain fatty acids includes mainly saturated fatty acids with one or more methyl branches in the iso or anteiso position. These fatty acids are largely derived from ruminal bacteria and they have been transferred to ruminant tissue (milk and meat). For that reason they have been used as biomarkers of rumen fermentation. Odd- and branched-chain fatty acids are exogenous products for humans, and therefore have specific properties. The results of research from recent decades show that odd- and branched-chain fatty acids have anti-cancer activity. Branched-chain fatty acids may reduce the incidence of necrotizing enterocolitis. Additionally, these compounds have a beneficial effect on proper tissue function and on functioning and development of the infant gut, whereas odd-chain fatty acids are considered as biomarkers of milk fat intake by humans. So far, not all the mechanisms of activity of these compounds are known thoroughly. They should be more carefully studied for application of their biological effects in prevention and treatment.

  8. Odd- and branched-chain fatty acids in milk fat – characteristic and health properties

    Directory of Open Access Journals (Sweden)

    Agata Adamska

    2014-08-01

    Full Text Available This review analyzes the current state of knowledge on odd- and branched-chain fatty acids present in milk fat. Special attention is devoted to the characteristic, synthesis in ruminants, factors affecting their content in milk fat and pro-health properties of these compounds. The group of odd- and branched-chain fatty acids includes mainly saturated fatty acids with one or more methyl branches in the iso or anteiso position. These fatty acids are largely derived from ruminal bacteria and they have been transferred to ruminant tissue (milk and meat. For that reason they have been used as biomarkers of rumen fermentation. Odd- and branched-chain fatty acids are exogenous products for humans, and therefore have specific properties. The results of research from recent decades show that odd- and branched-chain fatty acids have anti-cancer activity. Branched-chain fatty acids may reduce the incidence of necrotizing enterocolitis. Additionally, these compounds have a beneficial effect on proper tissue function and on functioning and development of the infant gut, whereas odd-chain fatty acids are considered as biomarkers of milk fat intake by humans. So far, not all the mechanisms of activity of these compounds are known thoroughly. They should be more carefully studied for application of their biological effects in prevention and treatment.

  9. Expression of Mitochondrial Branched-Chain Aminotransferase and α-Keto-Acid Dehydrogenase in Rat Brain: Implications for Neurotransmitter Metabolism

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-05-01

    Full Text Available In the brain, metabolism of the essential branched chain amino acids (BCAAs leucine, isoleucine and valine, is regulated in part by protein synthesis requirements. Excess BCAAs are catabolized or excreted. The first step in BCAA catabolism is catalyzed by the branched chain aminotransferase (BCAT isozymes, mitochondrial BCATm and cytosolic BCATc. A product of this reaction, glutamate, is the major excitatory neurotransmitter and precursor of the major inhibitory neurotransmitter -aminobutyric acid (GABA. The BCATs are thought to participate in an α-keto-acid nitrogen shuttle that provides nitrogen for synthesis of glutamate from -ketoglutarate. The branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC catalyzes the second and first irreversible step in BCAA metabolism, which is oxidative decarboxylation of the branched-chain α-keto acid (BCKA products of the BCAT reaction. Maple Syrup Urine Disease (MSUD results from genetic defects in BCKDC, which leads to accumulation of toxic levels of BCAAs and BCKAs that result in brain swelling. Immunolocalization of BCATm and BCKDC in rats revealed that BCATm is present in astrocytes in white matter and in neuropil, while BCKDC is expressed only in neurons. BCATm appears uniformly distributed in astrocyte cell bodies throughout the brain. The segregation of BCATm to astrocytes and BCKDC to neurons provides further support for the existence of a BCAA-dependent glial-neuronal nitrogen shuttle since the data show that BCKAs produced by glial BCATm must be exported to neurons. Additionally, the neuronal localization of BCKDC suggests that MSUD is a neuronal defect involving insufficient oxidation of BCKAs, with secondary effects extending beyond the neuron.

  10. Expression of mitochondrial branched-chain aminotransferase and α-keto-acid dehydrogenase in rat brain: implications for neurotransmitter metabolism

    Science.gov (United States)

    Cole, Jeffrey T.; Sweatt, Andrew J.; Hutson, Susan M.

    2012-01-01

    In the brain, metabolism of the essential branched chain amino acids (BCAAs) leucine, isoleucine, and valine, is regulated in part by protein synthesis requirements. Excess BCAAs are catabolized or excreted. The first step in BCAA catabolism is catalyzed by the branched chain aminotransferase (BCAT) isozymes, mitochondrial BCATm and cytosolic BCATc. A product of this reaction, glutamate, is the major excitatory neurotransmitter and precursor of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). The BCATs are thought to participate in a α-keto-acid nitrogen shuttle that provides nitrogen for synthesis of glutamate from α-ketoglutarate. The branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC) catalyzes the second, irreversible step in BCAA metabolism, which is oxidative decarboxylation of the branched-chain α-keto acid (BCKA) products of the BCAT reaction. Maple Syrup Urine Disease (MSUD) results from genetic defects in BCKDC, which leads to accumulation of toxic levels of BCAAs and BCKAs that result in brain swelling. Immunolocalization of BCATm and BCKDC in rats revealed that BCATm is present in astrocytes in white matter and in neuropil, while BCKDC is expressed only in neurons. BCATm appears uniformly distributed in astrocyte cell bodies throughout the brain. The segregation of BCATm to astrocytes and BCKDC to neurons provides further support for the existence of a BCAA-dependent glial-neuronal nitrogen shuttle since the data show that BCKAs produced by glial BCATm must be exported to neurons. Additionally, the neuronal localization of BCKDC suggests that MSUD is a neuronal defect involving insufficient oxidation of BCKAs, with secondary effects extending beyond the neuron. PMID:22654736

  11. Strong, Weak and Branching Bisimulation for Transition Systems and Markov Reward Chains: A Unifying Matrix Approach

    Directory of Open Access Journals (Sweden)

    Nikola Trčka

    2009-12-01

    Full Text Available We first study labeled transition systems with explicit successful termination. We establish the notions of strong, weak, and branching bisimulation in terms of boolean matrix theory, introducing thus a novel and powerful algebraic apparatus. Next we consider Markov reward chains which are standardly presented in real matrix theory. By interpreting the obtained matrix conditions for bisimulations in this setting, we automatically obtain the definitions of strong, weak, and branching bisimulation for Markov reward chains. The obtained strong and weak bisimulations are shown to coincide with some existing notions, while the obtained branching bisimulation is new, but its usefulness is questionable.

  12. Straight and branched-chain fatty acids in preorbital glands of sika deer, Cervus nippon.

    Science.gov (United States)

    Wood, William F

    2004-02-01

    Using GC-MS analysis, 11 major volatile compounds were found in the preorbital gland secretion from a female sika deer, Cervus nippon. These compounds are the C14 through C18 straight-chain fatty acids, (ZZ)-9,12-octadecadienoic acid, 12-methyltridecanoic acid, 13-methyltetradecanoic acid, 14-methylpentadecanoic acid, 14-methylhexadecanoic acid, and 15-methylhexadecanoic acid. The five branched-chain acids make up over 29% of the volatiles in the gland. This is the first time branched-chain carboxylic acids have been reported from ungulate preorbital glands.

  13. Association of Branched and Aromatic Amino Acids Levels with Metabolic Syndrome and Impaired Fasting Glucose in Hypertensive Patients

    OpenAIRE

    Weng, Liming; Quinlivan, Eoin; Gong, Yan; Beitelshees, Amber L.; Shahin, Mohamed H.; Turner, Stephen T.; Chapman, Arlene B.; Gums, John G.; Johnson, Julie A.; Frye, Reginald F.; Garrett, Timothy J.; Cooper-DeHoff, Rhonda M.

    2015-01-01

    Background: The three branched amino acids (valine, leucine, and isoleucine) and two aromatic amino acids (tyrosine and phenylalanine) have been associated with many adverse metabolic pathways, including diabetes. However, these associations have been identified primarily in otherwise healthy Caucasian populations. We aimed to investigate the association of this five-amino-acid signature with metabolic syndrome and impaired fasting glucose (IFG) in a hypertensive cohort of Caucasian and Afric...

  14. Measuring chain digitisation maturity: an assessment of Dutch retail branches.

    NARCIS (Netherlands)

    Plomp, M.G.A.; Batenburg, R.S.

    2010-01-01

    The purpose of this article is to develop a validated measurement model and typology for chain digitisation maturity, defined as the degree of interorganisational collaboration through ICT. The advantages of interorganisational information systems (IOIS) seem to meet the challenges currently facing

  15. Measuring chain digitisation maturity: an assessment of Dutch retail branches.

    NARCIS (Netherlands)

    Plomp, M.; Batenburg, R.

    2010-01-01

    The purpose of this article is to develop a validated measurement model and typology for chain digitisation maturity, defined as the degree of interorganisational collaboration through ICT. Design/methodology/approach: Through a literature (meta) study, 22 existing maturity models are found and

  16. Physiological covalent regulation of rat liver branched-chain alpha-ketoacid dehydrogenase

    International Nuclear Information System (INIS)

    Harris, R.A.; Powell, S.M.; Paxton, R.; Gillim, S.E.; Nagae, H.

    1985-01-01

    A radiochemical assay was developed for measuring branched-chain alpha-ketoacid dehydrogenase activity of Triton X-100 extracts of freeze-clamped rat liver. The proportion of active (dephosphorylated) enzyme was determined by measuring enzyme activities before and after activation of the complex with a broad-specificity phosphoprotein phosphatase. Hepatic branched-chain alpha-ketoacid dehydrogenase activity in normal male Wistar rats was 97% active but decreased to 33% active after 2 days on low-protein (8%) diet and to 13% active after 4 days on the same diet. Restricting protein intake of lean and obese female Zucker rats also caused inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex. Essentially all of the enzyme was in the active state in rats maintained for 14 days on either 30 or 50% protein diets. This was also the case for rats maintained on a commercial chow diet (minimum 23% protein). However, maintaining rats on 20, 8, and 0% protein diets decreased the percentage of the active form of the enzyme to 58, 10, and 7% of the total, respectively. Fasting of chow-fed rats for 48 h had no effect on the activity state of hepatic branched-chain alpha-ketoacid dehydrogenase, i.e., 93% of the enzyme remained in the active state compared to 97% for chow-fed rats. However, hepatic enzyme of rats maintained on 8% protein diet was 10% active before starvation and 83% active after 2 days of starvation. Thus, dietary protein deficiency results in inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex, presumably as a consequence of low hepatic levels of branched-chain alpha-ketoacids

  17. Electron beam curable branched chain polyurethane acrylates for magnetic media coatings

    International Nuclear Information System (INIS)

    Ukachi, Takashi; Haga, Kei-ichi; Matsumura, Yoshio

    1989-01-01

    Electron beam curable binder resins have been studied to realize the high quality magnetic coatings. It was supposed that resins with a higher crosslink density could lead to magnetic coatings with higher abrasion resistance. Branched chain polyurethane acrylates show a higher degree of cure by irradiation with an electron beam in comparison with linear polyurethane acrylates. This paper describes the potential wear resistance between properties of magnetic coatings and the physical properties of the cured unpigmented branched chain polyurethane acrylates that were used as the binder resins. (author)

  18. The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

    OpenAIRE

    Wagenmakers, A J; Schepens, J T; Veldhuizen, J A; Veerkamp, J H

    1984-01-01

    An assay is described to define the proportion of the branched-chain 2-oxo acid dehydrogenase complex that is present in the active state in rat tissues. Activities are measured in homogenates in two ways: actual activities, present in tissues, by blocking both the kinase and phosphatase of the enzyme complex during homogenization, preincubation, and incubation with 1-14C-labelled branched-chain 2-oxo acid, and total activities by blocking only the kinase during the 5 min preincubation (neces...

  19. 2-ethylhydracrylic aciduria in short/branched-chain acyl-CoA dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Korman, Stanley H; Andresen, Brage S; Zeharia, Avraham

    2005-01-01

    BACKGROUND: Isolated excretion of 2-methylbutyrylglycine (2-MBG) is the hallmark of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), a recently identified defect in the proximal pathway of L-isoleucine oxidation. SBCADD might be underdiagnosed because detection and recognition...

  20. Strong, weak and branching bisimulation for transition systems and Markov reward chains: A unifying matrix approach

    NARCIS (Netherlands)

    Trcka, N.; Andova, S.; McIver, A.; D'Argenio, P.; Cuijpers, P.J.L.; Markovski, J.; Morgan, C.; Núñez, M.

    2009-01-01

    We first study labeled transition systems with explicit successful termination. We establish the notions of strong, weak, and branching bisimulation in terms of boolean matrix theory, introducing thus a novel and powerful algebraic apparatus. Next we consider Markov reward chains which are

  1. 谷氨酰胺、EPA、支链氨基酸对食管癌同步放化疗及胃癌术后辅助化疗患者的影响%Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy

    Institute of Scientific and Technical Information of China (English)

    丛明华; 宋晨鑫; 邹宝华; 邓颖冰; 李淑娈; 刘雪辉; 刘微微; 刘金英; 于雷

    2015-01-01

    Objective To explore the effects of glutamine,eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy.Methods From April 2013 to April 2014,a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups.Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d),EPA (3.3 g/d) and branched-chain amino acids (8 g/d).And body compositions,blood indicators,incidence of complications and completion rates of therapy were compared between two groups.Results After treatment,free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P < 0.05).And albumin,red blood cell count,white blood cell count and blood platelet count remained stable in experiment group while declined significantly in control group.During treatment,compared to control group,the incidences of infection-associated complication were lower (6% vs 19%,P < 0.05) and the completion rates of therapy were significantly higher in experiment group (96% vs 83%,P < 0.05).Conclusion Supplements of glutamine,EPA and branched-chain amino acids can help maintain nutrition status,decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.%目的 观察补充谷氨酰胺、二十碳五烯酸(EPA)、支链氨基酸对食管癌同步放化疗及胃癌术后辅助化疗患者的作用.方法 2013年4月至2014年4月因食管癌、胃癌在中国医学科学院肿瘤医院和北京桓兴病区拟行化疗或同步化放疗患者104例入组,数字随机分为试验组和对照组进行营养干预,两组均进行

  2. Orientational cross correlations between entangled branch polymers in primitive chain network simulations

    Science.gov (United States)

    Masubuchi, Yuichi; Pandey, Ankita; Amamoto, Yoshifumi; Uneyama, Takashi

    2017-11-01

    Although it has not been frequently discussed, contributions of the orientational cross-correlation (OCC) between entangled polymers are not negligible in the relaxation modulus. In the present study, OCC contributions were investigated for 4- and 6-arm star-branched and H-branched polymers by means of multi-chain slip-link simulations. Owing to the molecular-level description of the simulation, the segment orientation was traced separately for each molecule as well as each subchain composing the molecules. Then, the OCC was calculated between different molecules and different subchains. The results revealed that the amount of OCC between different molecules is virtually identical to that of linear polymers regardless of the branching structure. The OCC between constituent subchains of the same molecule is significantly smaller than the OCC between different molecules, although its intensity and time-dependent behavior depend on the branching structure as well as the molecular weight. These results lend support to the single-chain models given that the OCC effects are embedded into the stress-optical coefficient, which is independent of the branching structure.

  3. Amino Acid Based Synthesis of Chiral Long Chain Diamines and Tetramines

    Directory of Open Access Journals (Sweden)

    George Kokotos

    2002-10-01

    Full Text Available A method for the synthesis of long chain diamines and tetramines starting from natural α-amino acids is reported. Diamines and tetramines were prepared through the Wittig olefination reaction of N-protected amino aldehydes obtained from phenylalanine and lysine. A 1,2,17,18-tetramine was synthesized using (2S-1-azido-2-[bis(tert-butoxycarbonyl-amino]-5-oxopentane as key-intermediate compound.

  4. Process for the selective cracking of straight-chained and slightly branched hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Gorring, R L; Shipman, G F

    1975-01-23

    The invention describes a method for the selective (hydro) cracking of petroleum materials, containing normal straight-chained and/or slightly branched-chained hydrocarbons. The mixture is brought into contact with a selective, crystalline alumino silicate zeolite cracking catalyst housing a silicon oxide/aluminum oxide ratio of at least about 12 and a constraint index of about 1 to 12 under cracking conditions. A zeolite catalyst with a crystal size of up to 0.05 ..mu.. is used. Solidification point and viscosity in particular of oils are to be lowered through the catalytic dewaxing.

  5. Internal logistics as a part of supply chain : case : Nokia-China, Dongguang Branch

    OpenAIRE

    Tian, Ran

    2009-01-01

    Internal logistics is one of the most important sections within enterprises, especially in the large manufacturing companies. It manages, arranges, plans and delivers the finished products. It is an indispensable part of the supply chain, as well as reflects the result of implementation company strategy. This study focuses on finding the possible ways to improve the operation process of Nokia-China internal logistics by looking into Nokia-China’s internal logistics in Dongguan Branch- Su...

  6. Disappearance of criticality in branched-chain thermal explosion with heat loss

    International Nuclear Information System (INIS)

    Okoya, Samuel S.

    2003-09-01

    In the framework of the currently developed branched-chain thermal explosion theory, the equation governing leakage through a hole of a reaction vessel is given. The critical ignition, extinction and transition temperature excess, activation energy parameter and modified Semenov's number are estimated employing this equation. We calculated numerically and obtained analytically these non-dimensional parameters with and without initiation respectively. The similar solution for Semenov model appear as a limiting case of our solution. We also obtained the ignition times. (author)

  7. Microbial synthesis of a branched-chain ester platform from organic waste carboxylates

    Directory of Open Access Journals (Sweden)

    Donovan S. Layton

    2016-12-01

    Full Text Available Processing of lignocellulosic biomass or organic wastes produces a plethora of chemicals such as short, linear carboxylic acids, known as carboxylates, derived from anaerobic digestion. While these carboxylates have low values and are inhibitory to microbes during fermentation, they can be biologically upgraded to high-value products. In this study, we expanded our general framework for biological upgrading of carboxylates to branched-chain esters by using three highly active alcohol acyltransferases (AATs for alcohol and acyl CoA condensation and modulating the alcohol moiety from ethanol to isobutanol in the modular chassis cell. With this framework, we demonstrated the production of an ester library comprised of 16 out of all 18 potential esters, including acetate, propionate, butanoate, pentanoate, and hexanoate esters, from the 5 linear, saturated C2-C6 carboxylic acids. Among these esters, 5 new branched-chain esters, including isobutyl acetate, isobutyl propionate, isobutyl butyrate, isobutyl pentanoate, and isobutyl hexanoate were synthesized in vivo. During 24 h in situ fermentation and extraction, one of the engineered strains, EcDL208 harnessing the SAAT of Fragaria ananassa produced ~63 mg/L of a mixture of butyl and isobutyl butyrates from glucose and butyrate co-fermentation and ~127 mg/L of a mixture of isobutyl and pentyl pentanoates from glucose and pentanoate co-fermentation, with high specificity. These butyrate and pentanoate esters are potential drop-in liquid fuels. This study provides better understanding of functional roles of AATs for microbial biosynthesis of branched-chain esters and expands the potential use of these esters as drop-in biofuels beyond their conventional flavor, fragrance, and solvent applications. Keywords: Carboxylate platform, Ester platform, Branched-chain ester, Modular cell, Biological upgrading, Organic waste, Lignocellulosic biomass, Isobutyl esters

  8. The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

    Science.gov (United States)

    Wagenmakers, A J; Schepens, J T; Veldhuizen, J A; Veerkamp, J H

    1984-05-15

    An assay is described to define the proportion of the branched-chain 2-oxo acid dehydrogenase complex that is present in the active state in rat tissues. Activities are measured in homogenates in two ways: actual activities, present in tissues, by blocking both the kinase and phosphatase of the enzyme complex during homogenization, preincubation, and incubation with 1-14C-labelled branched-chain 2-oxo acid, and total activities by blocking only the kinase during the 5 min preincubation (necessary for activation). The kinase is blocked by 5 mM-ADP and absence of Mg2+ and the phosphatase by the simultaneous presence of 50 mM-NaF. About 6% of the enzyme is active in skeletal muscle of fed rats, 7% in heart, 20% in diaphragm, 47% in kidney, 60% in brain and 98% in liver. An entirely different assay, which measures activities in crude tissue extracts before and after treatment with a broad-specificity protein phosphatase, gave similar results for heart, liver and kidney. Advantages of our assay with homogenates are the presence of intact mitochondria, the simplicity, the short duration and the high sensitivity. The actual activities measured indicate that the degradation of branched-chain 2-oxo acids predominantly occurs in liver and kidney and is limited in skeletal muscle in the fed state.

  9. Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice

    Science.gov (United States)

    Joshi, Mandar A.; Jeoung, Nam Ho; Obayashi, Mariko; Hattab, Eyas M.; Brocken, Eric G.; Liechty, Edward A.; Kubek, Michael J.; Vattem, Krishna M.; Wek, Ronald C.; Harris, Robert A.

    2006-01-01

    The BCKDH (branched-chain α-keto acid dehydrogenase complex) catalyses the rate-limiting step in the oxidation of BCAAs (branched-chain amino acids). Activity of the complex is regulated by a specific kinase, BDK (BCKDH kinase), which causes inactivation, and a phosphatase, BDP (BCKDH phosphatase), which causes activation. In the present study, the effect of the disruption of the BDK gene on growth and development of mice was investigated. BCKDH activity was much greater in most tissues of BDK−/− mice. This occurred in part because the E1 component of the complex cannot be phosphorylated due to the absence of BDK and also because greater than normal amounts of the E1 component were present in tissues of BDK−/− mice. Lack of control of BCKDH activity resulted in markedly lower blood and tissue levels of the BCAAs in BDK−/− mice. At 12 weeks of age, BDK−/− mice were 15% smaller than wild-type mice and their fur lacked normal lustre. Brain, muscle and adipose tissue weights were reduced, whereas weights of the liver and kidney were greater. Neurological abnormalities were apparent by hind limb flexion throughout life and epileptic seizures after 6–7 months of age. Inhibition of protein synthesis in the brain due to hyperphosphorylation of eIF2α (eukaryotic translation initiation factor 2α) might contribute to the neurological abnormalities seen in BDK−/− mice. BDK−/− mice show significant improvement in growth and appearance when fed a high protein diet, suggesting that higher amounts of dietary BCAA can partially compensate for increased oxidation in BDK−/− mice. Disruption of the BDK gene establishes that regulation of BCKDH by phosphorylation is critically important for the regulation of oxidative disposal of BCAAs. The phenotype of the BDK−/− mice demonstrates the importance of tight regulation of oxidative disposal of BCAAs for normal growth and neurological function. PMID:16875466

  10. Conversion of raw lignocellulosic biomass into branched long-chain alkanes through three tandem steps.

    Science.gov (United States)

    Li, Chunrui; Ding, Daqian; Xia, Qineng; Liu, Xiaohui; Wang, Yanqin

    2016-07-07

    Synthesis of branched long-chain alkanes from renewable biomass has attracted intensive interest in recent years, but the feedstock for this synthesis is restricted to platform chemicals. Here, we develop an effective and energy-efficient process to convert raw lignocellulosic biomass (e.g., corncob) into branched diesel-range alkanes through three tandem steps for the first time. Furfural and isopropyl levulinate (LA ester) were prepared from hemicellulose and cellulose fractions of corncob in toluene/water biphasic system with added isopropanol, which was followed by double aldol condensation of furfural with LA ester into C15 oxygenates and the final hydrodeoxygenation of C15 oxygenates into branched long-chain alkanes. The core point of this tandem process is the addition of isopropanol in the first step, which enables the spontaneous transfer of levulinic acid (LA) into the toluene phase in the form of LA ester through esterification, resulting in LA ester co-existing with furfural in the same phase, which is the basis for double aldol condensation in the toluene phase. Moreover, the acidic aqueous phase and toluene can be reused and the residues, including lignin and humins in aqueous phase, can be separated and carbonized to porous carbon materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Improving proton conduction pathways in di- and triblock copolymer membranes: Branched versus linear side chains

    Science.gov (United States)

    Dorenbos, G.

    2017-06-01

    Phase separation within a series of polymer membranes in the presence of water is studied by dissipative particle dynamics. Each polymer contains hydrophobic A beads and hydrophilic C beads. Three parent architectures are constructed from a backbone composed of connected hydrophobic A beads to which short ([C]), long ([A3C]), or symmetrically branched A5[AC][AC] side chains spring off. Three di-block copolymer derivatives are constructed by covalently bonding an A30 block to each parent architecture. Also three tri-blocks with A15 blocks attached to both ends of each parent architecture are modeled. Monte Carlo tracer diffusion calculations through the water containing pores for 1226 morphologies reveal that water diffusion for parent architectures is slowest and diffusion through the di-blocks is fastest. Furthermore, diffusion increases with side chain length and is highest for branched side chains. This is explained by the increase of water pore size with , which is the average number of bonds that A beads are separated from a nearest C bead. Optimization of within the amphiphilic parent architecture is expected to be essential in improving proton conduction in polymer electrolyte membranes.

  12. Biological Functions of ilvC in Branched-Chain Fatty Acid Synthesis and Diffusible Signal Factor Family Production in Xanthomonas campestris

    Directory of Open Access Journals (Sweden)

    Kai-Huai Li

    2017-12-01

    Full Text Available In bacteria, the metabolism of branched-chain amino acids (BCAAs is tightly associated with branched-chain fatty acids (BCFAs synthetic pathways. Although previous studies have reported on BCFAs biosynthesis, more detailed associations between BCAAs metabolism and BCFAs biosynthesis remain to be addressed. In this study, we deleted the ilvC gene, which encodes ketol-acid reductoisomerase in the BCAAs synthetic pathway, from the Xanthomonas campestris pv. campestris (Xcc genome. We characterized gene functions in BCFAs biosynthesis and production of the diffusible signal factor (DSF family signals. Disruption of ilvC caused Xcc to become auxotrophic for valine and isoleucine, and lose the ability to synthesize BCFAs via carbohydrate metabolism. Furthermore, ilvC mutant reduced the ability to produce DSF-family signals, especially branched-chain DSF-family signals, which might be the main reason for Xcc reduction of pathogenesis toward host plants. In this report, we confirmed that BCFAs do not have major functions in acclimatizing Xcc cells to low temperatures.

  13. Degradation of amino acids to short-chain fatty acids in humans. An in vitro study

    DEFF Research Database (Denmark)

    Rasmussen, H S; Holtug, K; Mortensen, P B

    1988-01-01

    Short-chain fatty acids (SCFA) originate mainly in the colon through bacterial fermentation of polysaccharides. To test the hypothesis that SCFA may originate from polypeptides as well, the production of these acids from albumin and specific amino acids was examined in a faecal incubation system....... Albumin was converted to all C2-C5-fatty acids, whereas amino acids generally were converted to specific SCFA, most often through the combination of a deamination and decarboxylation of the amino acids, although more complex processes also took place. This study indicates that a part of the intestinal...

  14. KEJADIAN INDEL SIMULTAN PADA INTRON 7 GEN BRANCHED-CHAIN Α-KETOACID DEHYDROGENASE E1A (BCKDHA PADA SAPI MADURA

    Directory of Open Access Journals (Sweden)

    Asri Febriana

    2015-08-01

    Full Text Available Madura cattle is one of the Indonesian local cattle breeds derived from crossing between Zebu cattle (Bos indicus and banteng (Bos javanicus. Branched-chain α-ketoacid dehydrogenase (BCKDH is one of the main enzyme complexes in the inner mitochondrial membrane that metabolizes branched chain amino acid (BCAA, ie valine, leucine, and isoleucine. The diversity of the nucleotide sequences of the genes largely determine the efficiency of enzyme encoded. This paper aimed to determine the nucleotide variation contained in section intron 7, exon 8, and intron 8 genes BCKDHA on Madura cattle. This study was conducted on three Madura cattle that used as bull race (karapan, beauty contest (sonok, and beef cattle. The analysis showed that the variation in intron higher than occurred in the exon. Simultaneous indel found at base position 34 and 68 in sonok cattle. In addition, the C266T variant found in beef cattle. These variants do not cause significant changes in amino acids. There was no specific mutation in intron 7, exon 8, and intron 8 were found in Madura cattle designation. This indicated the absence of differentiation Madura cattle designation of selection pressure of BCKDHA gene.

  15. Syn-Selective Synthesis of β-Branched α-Amino Acids by Alkylation of Glycine-Derived Imines with Secondary Sulfonates.

    Science.gov (United States)

    Lou, Sha; McKenna, Grace M; Tymonko, Steven A; Ramirez, Antonio; Benkovics, Tamas; Conlon, David A; González-Bobes, Francisco

    2015-10-16

    A syn-selective synthesis of β-branched α-amino acids has been developed based on the alkylation of glycine imine esters with secondary sulfonates. The potassium counterion for the enolate, the solvent, and the leaving group on the electrophile were key levers to maximize the diasteroselectivity of the alkylation. The optimized conditions enabled a straightforward preparation of a number of β-branched α-amino acids that can be challenging to obtain.

  16. Equilibrium polymerization of cyclic carbonate oligomers. III. Chain branching and the gel transition

    Science.gov (United States)

    Ballone, P.; Jones, R. O.

    2002-10-01

    Ring-opening polymerization of cyclic polycarbonate oligomers, where monofunctional active sites act on difunctional monomers to produce an equilibrium distribution of rings and chains, leads to a "living polymer." Monte Carlo simulations [two-dimensional (2D) and three-dimensional (3D)] of the effects of single [J. Chem. Phys. 115, 3895 (2001)] and multiple active sites [J. Chem. Phys. 116, 7724 (2002)] are extended here to trifunctional active sites that lead to branching. Low concentrations of trifunctional particles c3 reduce the degree of polymerization significantly in 2D, and higher concentrations (up to 32%) lead to further large changes in the phase diagram. Gel formation is observed at high total density and sizable c3 as a continuous transition similar to percolation. Polymer and gel are much more stable in 3D than in 2D, and both the total density and the value of c3 required to produce high molecular weight aggregates are reduced significantly. The degree of polymerization in high-density 3D systems is increased by the addition of trifunctional monomers and reduced slightly at low densities and low c3. The presence of branching makes equilibrium states more sensitive (in 2D and 3D) to changes in temperature T. The stabilities of polymer and gel are enhanced by increasing T, and—for sufficiently high values of c3—there is a reversible polymer-gel transformation at a density-dependent floor temperature.

  17. Branched-chain dicationic ionic liquids for fatty acid methyl ester assessment by gas chromatography.

    Science.gov (United States)

    Talebi, Mohsen; Patil, Rahul A; Sidisky, Leonard M; Berthod, Alain; Armstrong, Daniel W

    2017-12-06

    Twelve bis- or dicationic ionic liquids (ILs) including eight based on imidazolium, a single one based on phosphonium, and three based on pyrrolidinium cationic units were prepared with the bis(trifluoromethyl sulfonyl) imide anion. The two identical cationic moieties were attached by different alkyl spacers having three or five carbons and differing alkyl substituents attached to the spacer. The SLB-IL111 column, as the most polar commercial stationary phase known, was included in the study for comparison. Isothermal separations of a rapeseed oil fatty acid methyl ester (FAME) sample were used to study and compare the 12 IL-based column performances and selectivities. The retention times of the most retained methyl esters of lignoceric (C24:0) and erucic (C22:1) acids were used to estimate the IL polarity. The phosphonium dicationic IL column was, by far, the least polar. Imidazolium-based dicationic IL columns were the most polar. Polarity and selectivity for the FAME separation were somewhat related. The separation of a 37-FAME standard mixture allowed the investigation of selectivity variations observed on the 12 IL-based columns under temperature gradients up to 230 °C. The remarkable selectivity of the IL-based columns is demonstrated by the detailed analysis of the cis/trans C18:1 isomers of a partially hydrogenated vegetable oil sample on 30-m columns, separations competing with that done following an "official method" performed on a 100-m column. Graphical abstract Separation of fatty acid methyl esters on a 30-m 3m 2 C 5 (mpy) 2 . 2NTf 2 branched-chain dicationic IL-based column. Branched chain dicationic ILs show great selectivity for separation of cis/trans, ω-3/ω-6, and detailed analysis of cis/trans fats.

  18. Increase of Long-chain Branching by Thermo-oxidative Treatment of LDPE

    Science.gov (United States)

    Rolón-Garrido, Víctor H.; Luo, Jinji; Wagner, Manfred H.

    2011-07-01

    Low-density polyethylene (LDPE) was exposed to thermal and thermo-oxidative treatment at 170 °C, and subsequently characterized by linear-viscoelastic measurements and in uniaxial extension. The Molecular Stress Function (MSF) model was used to quantify the elongational viscosities measured. For the thermally treated samples, exposure times between 2 and 6 hours were applied. Formation of long-chain branching (LCB) was found to occur only during the first two hours of thermal treatment. At longer exposure times, no difference in the level of strain hardening was observed. This was quantified by use of the MSF model: the nonlinear parameter fmax2 increased from fmax2 = 14 for the virgin sample to fmax2 = 22 for the samples thermally treated between 2 and 6 hours. For the thermo-oxidatively treated samples, which were exposed to air during thermal treatment between 30 and 90 minutes, the level of strain hardening increases drastically up to fmax2 = 55 with increasing exposure times from 30 up to 75 min due to LCB formation, and then decreases for an exposure time of 90 minutes due to chain scission dominating LCB formation. The nonlinear parameter β of the MSF model was found to be β = 2 for all samples, indicating that the general type of the random branching structure remains the same under all thermal conditions. Consequently only the parameter fmax2 of the MSF model and the linear-viscoelastic spectra were required to describe quantitatively the experimental observations. The strain hardening index, which is sometimes used to quantify strain hardening, follows accurately the trend of the MSF model parameter fmax2.

  19. An exceptional series of phase transitions in hydrophobic amino acids with linear side chains

    Czech Academy of Sciences Publication Activity Database

    Görbitz, C.H.; Karen, P.; Dušek, Michal; Petříček, Václav

    2016-01-01

    Roč. 3, Sep (2016), s. 341-353 ISSN 2052-2525 R&D Projects: GA MŠk LO1603 EU Projects: European Commission(XE) CZ.2.16/3.1.00/24510 Institutional support: RVO:68378271 Keywords : amino acids * disorder * hydrogen bonding * modulated phases * phase transitions * side-chain stacking * polymorphism * molecular crystals Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 5.793, year: 2016

  20. Effects of clofibric acid on the activity and activity state of the hepatic branched-chain 2-oxo acid dehydrogenase complex.

    Science.gov (United States)

    Zhao, Y; Jaskiewicz, J; Harris, R A

    1992-01-01

    Feeding clofibric acid to rats caused little or no change in total activity of the liver branched-chain 2-oxo acid dehydrogenase complex (BCODC). No change in mass of liver BCODC was detected by immunoblot analysis in response to dietary clofibric acid. No changes in abundance of mRNAs for the BCODC E1 alpha, E1 beta and E2 subunits were detected by Northern-blot analysis. Likewise, dietary clofibric acid had no effect on the activity state of liver BCODC (percentage of enzyme in the dephosphorylated, active, form) of rats fed on a chow diet. However, dietary clofibric acid greatly increased the activity state of liver BCODC of rats fed on a diet deficient in protein. No stable change in liver BCODC kinase activity was found in response to clofibric acid in either chow-fed or low-protein-fed rats. Clofibric acid had a biphasic effect on flux through BCODC in hepatocytes prepared from low-protein-fed rats. Stimulation of BCODC flux at low concentrations was due to clofibric acid inhibition of BCODC kinase, which in turn allowed activation of BCODC by BCODC phosphatase. Inhibition of BCODC flux at high concentrations was due to direct inhibition of BCODC by clofibric acid. The results suggest that the effects of clofibric acid in vivo on branched-chain amino acid metabolism can be explained by the inhibitory effects of this drug on BCODC kinase. Images Fig. 2. Fig. 3. PMID:1637295

  1. RP-HPLC/MS-APCI Analysis of Branched Chain TAG Prepared by Precursor-Directed Biosynthesis with Rhodococcus erythropolis

    Czech Academy of Sciences Publication Activity Database

    Schreiberová, O.; Krulikovská, T.; Sigler, Karel; Čejková, A.; Řezanka, Tomáš

    2010-01-01

    Roč. 45, č. 8 (2010), s. 743-756 ISSN 0024-4201 R&D Projects: GA MŠk 2B08062 Institutional research plan: CEZ:AV0Z50200510 Keywords : Rhodococcus erythropolis * RP-HPLC/MS-APCI * Branched chain triacylglycerols Subject RIV: EE - Microbiology, Virology Impact factor: 2.151, year: 2010

  2. Regional myocardial extraction of a radioiodinated branched chain fatty acid during right ventricular pressure overload due to acute pulmonary hypertension

    International Nuclear Information System (INIS)

    Hurford, W.; Lowenstein, E.; Zapol, W.; Barlai-Kovach, M.; Livni, E.; Elmaleh, D.R.; Strauss, H.W.

    1985-01-01

    To determine whether branched chain fatty acid extraction is reduced during right ventricular (RV) dysfunction due to acute pulmonary artery hypertension, studies were done in 6 anesthetized dogs. Regional branched chain fatty acid extraction was measured by comparing the myocardial uptake of I-125 labeled 15-[p-(iodophenyl)]-3-methylpentadecanoic acid (I-PDA) to myocardial blood flow. Acute pulmonary hypertension was induced by incremental intravenous injection of 100 micron diameter glass beads into six pentobarbital anesthetized, mechanically ventilated dogs. Myocardial blood flow was measured by radiolabeled microspheres both under baseline conditions and during pulmonary hypertension. Mean RV pressure rose from 12 +- 2 (mean +- SEM) to 30 +-3mmHg resulting in a 225 +- 16% increase in RV stroke work. RV ejection fraction, as assessed by gated blood pool scans fell from 39 +- 2 to 18 +- 2%. Left ventricular (LV) pressures, stroke work and ejection fraction were unchanged. Myocardial blood flow increased 132 + 59% in the RV free wall and 67 +- 22% in the RV septum. LV blood flow was unchanged. Despite increased RV work and myocardial blood flow, no differences were noted in the branched chain fatty acid extraction ratios among LV or RV free walls or septum. The authors conclude that early RV dysfunction associated with pulmonary artery hypertension is not due to inadequate myocardial blood flow or branched chain fatty acid extraction

  3. Branched-chain aminoacids and retraining of patients with chronic obstructive lung disease.

    Science.gov (United States)

    Menier, R; Talmud, J; Laplaud, D; Bernard, M P

    2001-12-01

    The aim of this work was to improve the efficacy of rehabilitation by retraining, by oral supply in branched-chain aminoacids (BCAA). Patients with chronic respiratory insufficiency mainly suffer from obstructive bronchitis due to tobacco or asthma. Nutritional assessment is one of the components of respiratory rehabilitation, with retraining. Intense physical training for several days negativates the nitrogen balance, the beginning of a training programme for sedentary patients increases their need in proteins. An additional supply in branched-chain aminoacids increases proteic anabolism, by synthesis increase and catabolism slackening of proteins. Moreover it is known that exposure to high altitude reduces lean mass by inducing a muscular atrophy, which can be avoided by the BCAA provided. This leads to wonder if extra supply of BCAA could play similar role in muscular mass loss induced by pathological chronic hypoxia. The prospective and comparative survey carried out in Toki-Eder (private hospital in Cambo) consisted in supplying (during five weeks or more) 30 retrained patients suffering from chronic obstructive bronchitis, and in matching them with 30 witnesses (obstructive patients retrained without additional supply in BCAA). Their mean hypoxemia amounted to 7 torr for age. Each of them improved their reached maximal power, and their VO2 SL, very highly significantly. Each of them developed a moderate metabolic acidosis (whose possible mechanisms are discussed) and slightly increased their ventilation at rest. On the other hand only the supplied patients improved their PaO2 at rest highly significantly, a result which poses the question of the responsible mechanism, most likely a decrease of pulmonary shunt effect. The hypotheses concerning the acid load due to BCAA ingestion are discussed. Only the supplied patients developed hypocapnia expressing a gaseous alkalosis which might be due to a direct effect of BCAA on the respiratory centers. This observation

  4. Computational mining for hypothetical patterns of amino acid side chains in protein data bank (PDB)

    Science.gov (United States)

    Ghani, Nur Syatila Ab; Firdaus-Raih, Mohd

    2018-04-01

    The three-dimensional structure of a protein can provide insights regarding its function. Functional relationship between proteins can be inferred from fold and sequence similarities. In certain cases, sequence or fold comparison fails to conclude homology between proteins with similar mechanism. Since the structure is more conserved than the sequence, a constellation of functional residues can be similarly arranged among proteins of similar mechanism. Local structural similarity searches are able to detect such constellation of amino acids among distinct proteins, which can be useful to annotate proteins of unknown function. Detection of such patterns of amino acids on a large scale can increase the repertoire of important 3D motifs since available known 3D motifs currently, could not compensate the ever-increasing numbers of uncharacterized proteins to be annotated. Here, a computational platform for an automated detection of 3D motifs is described. A fuzzy-pattern searching algorithm derived from IMagine an Amino Acid 3D Arrangement search EnGINE (IMAAAGINE) was implemented to develop an automated method for searching of hypothetical patterns of amino acid side chains in Protein Data Bank (PDB), without the need for prior knowledge on related sequence or structure of pattern of interest. We present an example of the searches, which is the detection of a hypothetical pattern derived from known structural motif of C2H2 structural pattern from zinc fingers. The conservation of particular patterns of amino acid side chains in unrelated proteins is highlighted. This approach can act as a complementary method for available structure- and sequence-based platforms and may contribute in improving functional association between proteins.

  5. Stabilization of bacterially expressed erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites.

    Science.gov (United States)

    Hoffmann, E; Streichert, K; Nischan, N; Seitz, C; Brunner, T; Schwagerus, S; Hackenberger, C P R; Rubini, M

    2016-05-24

    The covalent attachment of polyethylene glycol (PEG) to therapeutic proteins can improve their physicochemical properties. In this work we utilized the non-natural amino acid p-azidophenylalanine (pAzF) in combination with the chemoselective Staudinger-phosphite reaction to install branched PEG chains to recombinant unglycosylated erythropoietin (EPO) at each single naturally occurring glycosylation site. PEGylation with two short 750 or 2000 Da PEG units at positions 24, 38, or 83 significantly decreased unspecific aggregation and proteolytic degradation while biological activity in vitro was preserved or even increased in comparison to full-glycosylated EPO. This site-specific bioconjugation approach permits to analyse the impact of PEGylation at single positions. These results represent an important step towards the engineering of site-specifically modified EPO variants from bacterial expression with increased therapeutic efficacy.

  6. Subcritical Water Hydrolysis of Peptides: Amino Acid Side-Chain Modifications

    Science.gov (United States)

    Powell, Thomas; Bowra, Steve; Cooper, Helen J.

    2017-09-01

    Previously we have shown that subcritical water may be used as an alternative to enzymatic digestion in the proteolysis of proteins for bottom-up proteomics. Subcritical water hydrolysis of proteins was shown to result in protein sequence coverages greater than or equal to that obtained following digestion with trypsin; however, the percentage of peptide spectral matches for the samples treated with trypsin were consistently greater than for those treated with subcritical water. This observation suggests that in addition to cleavage of the peptide bond, subcritical water treatment results in other hydrolysis products, possibly due to modifications of amino acid side chains. Here, a model peptide comprising all common amino acid residues (VQSIKCADFLHYMENPTWGR) and two further model peptides (VCFQYMDRGDR and VQSIKADFLHYENPTWGR) were treated with subcritical water with the aim of probing any induced amino acid side-chain modifications. The hydrolysis products were analyzed by direct infusion electrospray tandem mass spectrometry, either collision-induced dissociation or electron transfer dissociation, and liquid chromatography collision-induced dissociation tandem mass spectrometry. The results show preferential oxidation of cysteine to sulfinic and sulfonic acid, and oxidation of methionine. In the absence of cysteine and methionine, oxidation of tryptophan was observed. In addition, water loss from aspartic acid and C-terminal amidation were observed in harsher subcritical water conditions. [Figure not available: see fulltext.

  7. Direct evidence for the inactivation of branched-chain oxo-acid dehydrogenase by enzyme phosphorylation

    International Nuclear Information System (INIS)

    Odessey, R.

    1980-01-01

    The branched-chain 2-oxo-acid dehydrogenase (BCOAD) from mitochondria of several different rat tissues is inactivated by ATP and can be reactivated by incubation in Mg 2+ -containing buffers. Work carried out on the system from skeletal muscle mitochondria has shown that inactivation requires the cleavage of the γ-phosphate group of ATP and that modification is covalent. The non-metabolized ATP analog, p[NH]ppA, can block the inhibitory effect of ATP when added prior to ATP addition, but cannot reverse the inhibition of the inactivated dehydrogenase. These and other data raise the possibility that BCOAD may be regulated by enzyme phosphorylation. This hypothesis is supported by the finding that various procedures which separate the enzyme from its mitochondrial environment (e.g. detergent treatment, ammonium sulfate precipitation and freeze-thawing) do not alter the degree of inhibition induced by ATP in the mitochondrial preincubation. These experiments suggested the feasibility of labelling the enzyme with 32 P and purifying it. (Auth.)

  8. Measuring hydroperoxide chain-branching agents during n-pentane low-temperature oxidation

    KAUST Repository

    Rodriguez, Anne

    2016-06-23

    The reactions of chain-branching agents, such as HO and hydroperoxides, have a decisive role in the occurrence of autoignition. The formation of these agents has been investigated in an atmospheric-pressure jet-stirred reactor during the low-temperature oxidation of n-pentane (initial fuel mole fraction of 0.01, residence time of 2s) using three different diagnostics: time-of-flight mass spectrometry combined with tunable synchrotron photoionization, time-of-flight mass spectrometry combined with laser photoionization, and cw-cavity ring-down spectroscopy. These three diagnostics enable a combined analysis of HO, C-C, and C alkylhydroperoxides, C-C alkenylhydroperoxides, and C alkylhydroperoxides including a carbonyl function (ketohydroperoxides). Results using both types of mass spectrometry are compared for the stoichiometric mixture. Formation data are presented at equivalence ratios from 0.5 to 2 for these peroxides and of two oxygenated products, ketene and pentanediones, which are not usually analyzed during jet-stirred reactor oxidation. The formation of alkenylhydroperoxides during alkane oxidation is followed for the first time. A recently developed model of n-pentane oxidation aids discussion of the kinetics of these products and of proposed pathways for C-C alkenylhydroperoxides and the pentanediones.

  9. Diversification of Transcriptional Regulation Determines Subfunctionalization of Paralogous Branched Chain Aminotransferases in the Yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    González, James; López, Geovani; Argueta, Stefany; Escalera-Fanjul, Ximena; El Hafidi, Mohammed; Campero-Basaldua, Carlos; Strauss, Joseph; Riego-Ruiz, Lina; González, Alicia

    2017-11-01

    Saccharomyces cerevisiae harbors BAT1 and BAT2 paralogous genes that encode branched chain aminotransferases and have opposed expression profiles and physiological roles . Accordingly, in primary nitrogen sources such as glutamine, BAT1 expression is induced, supporting Bat1-dependent valine-isoleucine-leucine (VIL) biosynthesis, while BAT2 expression is repressed. Conversely, in the presence of VIL as the sole nitrogen source, BAT1 expression is hindered while that of BAT2 is activated, resulting in Bat2-dependent VIL catabolism. The presented results confirm that BAT1 expression is determined by transcriptional activation through the action of the Leu3-α-isopropylmalate (α-IPM) active isoform, and uncovers the existence of a novel α-IPM biosynthetic pathway operating in a put3 Δ mutant grown on VIL, through Bat2-Leu2-Leu1 consecutive action. The classic α-IPM biosynthetic route operates in glutamine through the action of the leucine-sensitive α-IPM synthases. The presented results also show that BAT2 repression in glutamine can be alleviated in a ure2 Δ mutant or through Gcn4-dependent transcriptional activation. Thus, when S. cerevisiae is grown on glutamine, VIL biosynthesis is predominant and is preferentially achieved through BAT1 ; while on VIL as the sole nitrogen source, catabolism prevails and is mainly afforded by BAT2 . Copyright © 2017 by the Genetics Society of America.

  10. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels

    DEFF Research Database (Denmark)

    Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T

    2017-01-01

    variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. RESULTS: Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10(-7)). However......, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0......(-4), and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p = 0.002). CONCLUSIONS/INTERPRETATION: Our...

  11. In Vivo Imaging of Branched Chain Amino Acid Metabolism in Prostate Cancer

    Science.gov (United States)

    2014-10-01

    BCAT levels in murine lymphoma ( EL4 ), a tumor with high BCAT activity.14 Although as yet unstudied using hyperpolarized 13C MRS techniques, recent...correlate with BCAT levels in murine lymphoma ( EL4 ), a tumor with high BCAT activity [16]. Although unstudied using hyperpolarized 13C MRS techniques

  12. An exceptional series of phase transitions in hydrophobic amino acids with linear side chains

    Directory of Open Access Journals (Sweden)

    Carl Henrik Görbitz

    2016-09-01

    Full Text Available The solid-state phase transitions and intermediate structures of S-2-aminobutanoic acid (l-2-aminobutyric acid, S-2-aminopentanoic acid (l-norvaline, S-2-aminohexanoic acid (l-norleucine and l-methionine between 100 and 470 K, identified by differential scanning calorimetry, have been characterized in a comprehensive single-crystal X-ray diffraction investigation. Unlike other enantiomeric amino acids investigated until now, this group featuring linear side chains displays up to five distinct phases. The multiple transitions between them involve a number of different processes: alteration of the hydrogen-bond pattern, to our knowledge the first example of this observed for an amino acid, sliding of molecular bilayers, seen previously only for racemates and quasiracemates, concerted side-chain rearrangements and abrupt as well as gradual modifications of the side-chain disorder. Ordering of l-norleucine upon cooling even proceeds via an incommensurately modulated structure. l-Methionine has previously been described as being fully ordered at room temperature. An accurate refinement now reveals extensive disorder for both molecules in the asymmetric unit, while two previously unknown phases occur above room temperature.

  13. Structure of antigenetic determinants in the amino-terminal region of bovine fibrinogen Aα chain

    International Nuclear Information System (INIS)

    Tanswell, P.; Reiter, H.; Timpl, R.

    1978-01-01

    A radioimmunoassay was developed for peptide F-CB1α from the amino of bovine fibrinogen Aα chain, isolated after reduction and carboxymethylation of the multichain disulfide-linked cyanogen bromide peptide F-CB1. Seven out of twelve different rabbit antisera produced against fibrinogen, peptide F-CB1 or Aα chain showed distinct binding to 125 I-labelled F-CB1α. Thrombin cleavage of F-CB1α yielded two fragments: fibrinopeptide A (residues 1-19) and the carboxy-terminal fragment Th2 (residues 20-54). Antisera could be classified into three groups according to whether they recognized antigenic determinants on fibrinopeptide A, on peptide Th2 or as they showed diminished reactions with both fragments. Only little or no cross-reaction was observed with the amino-terminal cyanogen bromide peptides of Bβ and γ chain. Proteolytic fragments of fibrinopeptide A were isolated and tested for inhibitory activity with two antisera. One antiserum contained anitbodies binding selectively to the amino-terminal sequence (residues 4-11) and did not cross-react with human fibrinopeptide A. Another antiserum showed a specific binding restricted to the carboxy-terminal sequence (residues 11-18) and cross-reacted completely with human fibrinopeptide A. These results correlate well with the primary structures of the two fibrinopeptides. The antigenic activity of the peptide fragment Th2 was localized on a 15-residue tryptic peptide derived from the central portion of the sequence. These and further data indicate that at least six different antigenic determinants are present in peptide F-CB1α. (orig.) 891 AJ [de

  14. Effect of Supplementation of Branched Chain Fatty Acid on Colony of Ruminal Bacteria and Cell of Protozoa

    Directory of Open Access Journals (Sweden)

    W Suryapratama

    2009-05-01

    Full Text Available A study was conducted to evaluate the potential of branched-chain volatile fatty acids (isobutyric, α-methylbutyric and β-methylbutiric that supplemented into the diet on the colony of ruminal bacteria and the cell of protozoa population. Five progeny Friesian Holstein males with initial weight 348±29 kg were used in a 5x5 Latin square design (30-d periods. The basal diet composed of 55% forage and 45% concentrate containing 10.5 MJ ME/kg and 15% crude protein (CP. There were five dietary treatments where A: basal diet, B: A+139 mg urea/kg W0.75, C: B+28 mg CaSO4/kg W0.75, D: C+0.05 mM isobutyric acid+0.05 mM β-methylbutyric acid, and E: D+0.05 mM α-methylbutyric acid. Rearing period was 30 days, consists of feed adaptation period 20 days, then growth observation was done within the last 10 days. Collection of ruminal fluid was done within the last day of observation period, and took 3-4 h after the feeding. The results showed that supplementation branched chain volatile fatty acids did not significant affect on the number of colonies of bacteria and protozoa population, but the significant effect (P<0.05 on the concentration of branched chain volatile fatty acids in the rumen fluid. The supplementation of α-methylbutyric (P <0.05 decreased of concentration of isobutyric and isovaleric in rumen fluid than the other treatments. It is concluded that supplementation of branched chain volatile fatty acids not used by rumen bacteria for their growth but for the elongation of fatty acid synthesis. The supplementation of branched chain volatile fatty acids was 0.05 mM not enough strong influence on the growth of colony of rumen bacteria. (Animal Production 11(2: 129-134 (2009 Key Words: rumen fermentation, branched-chain fatty acid, ruminal bacteria, protozoa

  15. Electron detachment of the hydrogen-bonded amino acid side-chain guanine complexes

    Science.gov (United States)

    Wang, Jing; Gu, Jiande; Leszczynski, Jerzy

    2007-07-01

    The photoelectron spectra of the hydrogen-bonded amino acid side-chain-guanine complexes has been studied at the partial third order (P3) self-energy approximation of the electron propagator theory. The correlation between the vertical electron detachment energy and the charge distributions on the guanine moiety reveals that the vertical electron detachment energy (VDE) increases as the positive charge distribution on the guanine increases. The low VDE values determined for the negatively charged complexes of the guanine-side-chain-group of Asp/Glu suggest that the influence of the H-bonded anionic groups on the VDE of guanine could be more important than that of the anionic backbone structure. The even lower vertical electron detachment energy for guanine is thus can be expected in the H-bonded protein-DNA systems.

  16. Microbial production of branched-chain dicarboxylate 2-methylsuccinic acid via enoate reductase-mediated bioreduction.

    Science.gov (United States)

    Wang, Jian; Yang, Yaping; Zhang, Ruihua; Shen, Xiaolin; Chen, Zhenya; Wang, Jia; Yuan, Qipeng; Yan, Yajun

    2018-01-01

    2-Methylsuccinic acid (2-MSA) is a C5 branched-chain dicarboxylate that serves as an attractive synthon for the synthesis of polymers with extensive applications in coatings, cosmetic solvents and bioplastics. However, the lack of natural pathways for 2-MSA biosynthesis has limited its application as a promising bio-replacement. Herein, we conceived a non-natural three-step biosynthetic route for 2-MSA, via employing the citramalate pathway in combination with enoate reductase-mediated bioreduction of the pathway intermediate citraconate. First, over-expression of codon-optimized citramalate synthase variant CimA* from Methanococcus jannaschii, endogenous isopropylmalate isomerase EcLeuCD and enoate reductase YqjM from Bacillus subtilis allowed the production of 2-MSA in Escherichia coli for the first time, with a titer of 0.35g/L in shake flask experiments. Subsequent screening of YqjM-like enoate reductases of different bacterial origins enabled identification and characterization of a new NAD(P)H-dependent enoate reductase KpnER from Klebsiella pneumoniae, which exhibited higher activity towards citraconate than YqjM. Incorporation of KpnER into the 2-MSA biosynthetic pathway led to 2-MSA production improvement to a titer of 0.96g/L in aerobic condition. Subsequent optimizations including cofactor regeneration, microaerobic cultivation and host strain engineering, boosted 2-MSA titer to 3.61g/L with a molar yield of 0.36 in shake flask experiments. This work established a promising platform for 2-MSA bioproduction, which enabled the highest titer of 2-MSA production in microbial hosts so far. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  17. New paradigm for simplified combustion modeling of energetic solids: Branched chain gas reaction

    Energy Technology Data Exchange (ETDEWEB)

    Brewster, M.Q.; Ward, M.J. [Univ. of Illinois, Urbana, IL (United States); Son, S.F. [Los Alamos National Lab., NM (United States)

    1997-09-01

    Two combustion models with simple but rational chemistry are compared: the classical high gas activation energy (E{sub g}/RT {much_gt} 1) Denison-Baum-Williams (DBW) model, and a new low gas activation energy (E{sub g}/RT {much_lt} 1) model recently proposed by Ward, Son, and Brewster (WSB). Both models make the same simplifying assumptions of constant properties, Lewis number unity, single-step, second order gas phase reaction, and single-step, zero order, high activation energy condensed phase decomposition. The only difference is in the gas reaction activation energy E{sub g} which is asymptotically large for DBW and vanishingly small for WSB. For realistic parameters the DBW model predicts a nearly constant temperature sensitivity {sigma}{sub p} and a pressure exponent n approaching 1. The WSB model predicts generally observed values of n = 0.7 to 0.9 and {sigma}{sub p}(T{sub o},P) with the generally observed variations with temperature (increasing) and pressure (decreasing). The WSB temperature profile also matches measured profiles better. Comparisons with experimental data are made using HMX as an illustrative example (for which WSB predictions for {sigma}{sub p}(T{sub o},P) are currently more accurate than even complex chemistry models). WSB has also shown good agreement with NC/NG double base propellant and HNF, suggesting that at the simplest level of combustion modeling, a vanishingly small gas activation energy is more realistic than an asymptotically large one. The authors conclude from this that the important (regression rate determining) gas reaction zone near the surface has more the character of chain branching than thermal decomposition.

  18. Structural characterization of saturated branched chain fatty acid methyl esters by collisional dissociation of molecular ions generated by electron ionization.

    Science.gov (United States)

    Ran-Ressler, Rinat R; Lawrence, Peter; Brenna, J Thomas

    2012-01-01

    Saturated branched chain fatty acids (BCFA) are present as complex mixtures in numerous biological samples. The traditional method for structure elucidation, electron ionization (EI) mass spectrometry, sometimes does not unambiguously enable assignment of branching in isomeric BCFA. Zirrolli and Murphy (Zirrolli , J. A. , and R. A. Murphy. 1993. Low-energy tandem mass spectrometry of the molecular ion derived from fatty acid methyl esters: a novel method for analysis of branched-chain fatty acids. J. Am. Soc. Mass Spectrom. 4: 223-229.) showed that the molecular ions of four BCFA methyl ester (BCFAME) yield highly characteristic fragments upon collisional dissociation using a triple quadrupole instrument. Here, we confirm and extend these results by analysis using a tabletop 3-D ion trap for activated molecular ion EI-MS/MS to 30 BCFAME. iso-BCFAME produces a prominent ion (30-100% of base peak) for [M-43] (M-C₃H₇), corresponding to the terminal isopropyl moiety in the original iso-BCFAME. Anteiso-FAME yield prominent ions (20-100% of base peak) corresponding to losses on both side of the methyl branch, [M-29] and [M-57], and tend to produce more prominent m/z 115 peaks corresponding to a cyclization product around the ester. Dimethyl and tetramethyl FAME, with branches separated by at least one methylene group, yield fragment on both sides of the sites of methyl branches that are more than 6 C away from the carboxyl carbon. EI-MS/MS yields uniquely specific ions that enable highly confident structural identification and quantification of BCFAME.

  19. Leucine-induced activation of translational initiation is partly regulated by the branched-chain α-keto acid dehydrogenase complex in C2C12 cells

    International Nuclear Information System (INIS)

    Nakai, Naoya; Shimomura, Yoshiharu; Tamura, Tomohiro; Tamura, Noriko; Hamada, Koichiro; Kawano, Fuminori; Ohira, Yoshinobu

    2006-01-01

    Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain α-keto acid dehydrogenase (BCKDH) complex. The complex contains E1 (α2β2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1α subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2C12 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48 h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex

  20. Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients.

    Science.gov (United States)

    García-Cazorla, Angels; Oyarzabal, Alfonso; Fort, Joana; Robles, Concepción; Castejón, Esperanza; Ruiz-Sala, Pedro; Bodoy, Susanna; Merinero, Begoña; Lopez-Sala, Anna; Dopazo, Joaquín; Nunes, Virginia; Ugarte, Magdalena; Artuch, Rafael; Palacín, Manuel; Rodríguez-Pombo, Pilar; Alcaide, Patricia; Navarrete, Rosa; Sanz, Paloma; Font-Llitjós, Mariona; Vilaseca, Ma Antonia; Ormaizabal, Aida; Pristoupilova, Anna; Agulló, Sergi Beltran

    2014-04-01

    Inactivating mutations in the BCKDK gene, which codes for the kinase responsible for the negative regulation of the branched-chain α-keto acid dehydrogenase complex (BCKD), have recently been associated with a form of autism in three families. In this work, two novel exonic BCKDK mutations, c.520C>G/p.R174G and c.1166T>C/p.L389P, were identified at the homozygous state in two unrelated children with persistently reduced body fluid levels of branched-chain amino acids (BCAAs), developmental delay, microcephaly, and neurobehavioral abnormalities. Functional analysis of the mutations confirmed the missense character of the c.1166T>C change and showed a splicing defect r.[520c>g;521_543del]/p.R174Gfs1*, for c.520C>G due to the presence of a new donor splice site. Mutation p.L389P showed total loss of kinase activity. Moreover, patient-derived fibroblasts showed undetectable (p.R174Gfs1*) or barely detectable (p.L389P) levels of BCKDK protein and its phosphorylated substrate (phospho-E1α), resulting in increased BCKD activity and the very rapid BCAA catabolism manifested by the patients' clinical phenotype. Based on these results, a protein-rich diet plus oral BCAA supplementation was implemented in the patient homozygous for p.R174Gfs1*. This treatment normalized plasma BCAA levels and improved growth, developmental and behavioral variables. Our results demonstrate that BCKDK mutations can result in neurobehavioral deficits in humans and support the rationale for dietary intervention. © 2014 WILEY PERIODICALS, INC.

  1. Isolation and amino acid sequence of a short-chain neurotoxin from an Australian elapid snake, Pseudechis australis.

    OpenAIRE

    Takasaki, C; Tamiya, N

    1985-01-01

    A short-chain neurotoxin Pseudechis australis a (toxin Pa a) was isolated from the venom of an Australian elapid snake Pseudechis australis (king brown snake) by sequential chromatography on CM-cellulose, Sephadex G-50 and CM-cellulose columns. Toxin Pa a has an LD50 (intravenous) value of 76 micrograms/kg body wt. in mice and consists of 62 amino acid residues. The amino acid sequence of Pa a shows considerable homology with those of short-chain neurotoxins of elapid snakes, especially of tr...

  2. 1H NMR analysis of long-chain-branched strong polyelectrolytes obtained by vinyl/divinyl monomer copolymerization in aqueous medium

    Czech Academy of Sciences Publication Activity Database

    Podešva, Jiří; Spěváček, Jiří; Kratochvíl, Pavel; Netopilík, Miloš

    2013-01-01

    Roč. 18, č. 7 (2013), s. 557-565 ISSN 1023-666X Institutional support: RVO:61389013 Keywords : long-chain branching * NMR * polyelectrolytes Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.487, year: 2013

  3. Self-assembly of long chain fatty acids: Effect of a methyl branch

    DEFF Research Database (Denmark)

    Liljeblad, Jonathan F. D.; Tyrode, Eric; Thormann, Esben

    2014-01-01

    chains of the straight chain fatty acids appear to be oriented perpendicular to the sample surface, based on an orientational analysis of VSFS data and the odd/even effect. In addition, the selection of the subphase (neat water or CdCl2 containing water buffered to pH 6.0) used for the LB-deposition has...

  4. Evaluation of branched chain fatty acid, BMIPP [β-methyl-ω-(p-iodophenyl)-pentadecanoic acid] for the myocardial imaging

    International Nuclear Information System (INIS)

    Kawamura, Yasuaki; Morishita, Takeshi; Yamazaki, Junichi

    1988-01-01

    Iodine-123 labeled branched chain fatty acid BMIPP [ β -methyl-ω-(p-iodophenyl)-pentadecanoic acid] was evaluated for the myocardial imaging experimentally. 123 I-BMIPP was accumulated in the heart at 2 - 4 minutes after injection and retention in the heart was remarkable at 30 minutes. In the acute canine infarction model, infarcted area was recognized as a defect. Furthermore, in comparison between 123 I-BMIPP and 201 Tl-Cl, discrepancy between these images was recognized in the ischemic and infarcted area. BMIPP is of use in not only cardiomyopathy and hypertension, but ischemic heart desease. (author)

  5. Peroxisome protein transportation affects metabolism of branched-chain fatty acids that critically impact growth and development of C. elegans.

    Directory of Open Access Journals (Sweden)

    Rencheng Wang

    Full Text Available The impact of specific lipid molecules, including fatty acid variants, on cellular and developmental regulation is an important research subject that remains under studied. Monomethyl branched-chain fatty acids (mmBCFAs are commonly present in multiple organisms including mammals, however our understanding of mmBCFA functions is very limited. C. elegans has been the premier model system to study the functions of mmBCFAs and their derived lipids, as mmBCFAs have been shown to play essential roles in post-embryonic development in this organism. To understand more about the metabolism of mmBCFAs in C. elegans, we performed a genetic screen for suppressors of the L1 developmental arrest phenotype caused by mmBCFA depletion. Extensive characterization of one suppressor mutation identified prx-5, which encodes an ortholog of the human receptor for the type-1 peroxisomal targeting signal protein. Our study showed that inactivating prx-5 function compromised the peroxisome protein import, resulting in an increased level of branched-chain fatty acid C17ISO in animals lacking normal mmBCFA synthesis, thereby restoring wild-type growth and development. This work reveals a novel connection between peroxisomal functions and mmBCFA metabolism.

  6. Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials123

    OpenAIRE

    Zheng, Yan; Ceglarek, Uta; Huang, Tao; Li, Lerong; Rood, Jennifer; Ryan, Donna H; Bray, George A; Sacks, Frank M; Schwarzfuchs, Dan; Thiery, Joachim; Shai, Iris; Qi, Lu

    2016-01-01

    Background: Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associated with diabetes risk; however, little is known about how a long-term dietary intervention for weight loss affects circulating amino acids.

  7. Oblique strain partitioning and transpression on an inverted rift: The Castilian Branch of the Iberian Chain

    NARCIS (Netherlands)

    Vicente, G. de; Vegas, R.; Muñoz-Martín, A.; Wees, J.D.A.M. van; Casas-Sáinz, A.; Sopeña, A.; Sánchez-Moya, Y.; Arche, A.; López-Gómez, J.; Olaiz, A.; Fernández-Lozano, J.

    2009-01-01

    The Iberian Chain is a wide intraplate deformation zone formed by the tectonic inversion during the Pyrenean orogeny of a Permian-Mesozoic basin developed in the eastern part of the Iberian Massif. The N-S convergence between Iberia and Eurasia from the Late Cretaceous to the Lower Miocene times

  8. Characterization of a novel debranching enzyme from Nostoc punctiforme possessing a high specificity for long branched chains

    International Nuclear Information System (INIS)

    Choi, Ji-Hye; Lee, Heeseob; Kim, Young-Wan; Park, Jong-Tae; Woo, Eui-Jeon; Kim, Myo-Jeong; Lee, Byong-Hoon; Park, Kwan-Hwa

    2009-01-01

    A novel debranching enzyme from Nostoc punctiforme PCC73102 (NPDE) exhibits hydrolysis activity toward both α-(1,6)- and α-(1,4)-glucosidic linkages. The action patterns of NPDE revealed that branched chains are released first, and the resulting maltooligosaccharides are then hydrolyzed. Analysis of the reaction with maltooligosaccharide substrates labeled with 14 C-glucose at the reducing end shows that NPDE specifically liberates glucose from the reducing end. Kinetic analyses showed that the hydrolytic activity of NPDE is greatly affected by the length of the substrate. The catalytic efficiency of NPDE increased considerably upon using substrates that can occupy at least eight glycone subsites such as maltononaose and maltooctaosyl-α-(1,6)-β-cyclodextrin. These results imply that NPDE has a unique subsite structure consisting of -8 to +1 subsites. Given its unique subsite structure, side chains shorter than maltooctaose in amylopectin were resistant to hydrolysis by NPDE, and the population of longer side chains was reduced.

  9. Modified solution calorimetry approach for determination of vaporization and sublimation enthalpies of branched-chain aliphatic and alkyl aromatic compounds at T = 298.15 K

    International Nuclear Information System (INIS)

    Varfolomeev, Mikhail A.; Novikov, Vladimir B.; Nagrimanov, Ruslan N.; Solomonov, Boris N.

    2015-01-01

    Highlights: • Solution enthalpies of 18 branching-chain alkyl aromatic and aliphatic compounds in cyclohexane were measured. • Group contributions to the enthalpy of solvation due to branching and substitution in carbon chain were evaluated. • Modified solution calorimetry based approach for determination of vaporization/sublimation enthalpies was proposed. • This approach provides vaporization/sublimation enthalpies directly at T = 298.15 K. • Vaporization/sublimation enthalpies of 35 branched-chain alkyl aromatic and aliphatic compounds were determined. - Abstract: The enthalpies of solution, solvation and vaporization/sublimation are interrelated values combined in the simplest thermodynamic circle. Hence, experimental determination of vaporization/sublimation enthalpy can be substituted by experimentally simpler determination of solution enthalpy when solvation enthalpy is known. Previously it was found that solvation enthalpies of a wide range of unbranched aliphatic and aromatic solutes in saturated hydrocarbons are in good linear correlation with their molar refraction values. This allows to estimate the vaporization/sublimation enthalpy of any unbranched organic compound from its solution enthalpy in saturated hydrocarbon and molar refraction. In the present work this approach was modified for determination of vaporization/sublimation enthalpy of branched-chain alkyl aromatic and aliphatic compounds. Group contributions to the enthalpy of solvation due to the branching of carbon chain were evaluated. Enthalpies of solution at infinite dilution of 18 branched-chain aliphatic and alkyl aromatic compounds were measured at T = 298.15 K. Vaporization/sublimation enthalpies for 35 branched aliphatic and alkyl aromatic compounds were determined by using modified solution calorimetry approach. These values are in good agreement with available literature data on vaporization/sublimation enthalpies obtained by conventional methods.

  10. The amino acid sequences of two alpha chains of hemoglobins from Komodo dragon Varanus komodoensis and phylogenetic relationships of amniotes.

    Science.gov (United States)

    Fushitani, K; Higashiyama, K; Moriyama, E N; Imai, K; Hosokawa, K

    1996-09-01

    To elucidate phylogenetic relationships among amniotes and the evolution of alpha globins, hemoglobins were analyzed from the Komodo dragon (Komodo monitor lizard) Varanus komodoensis, the world's largest extant lizard, inhabiting Komodo Islands, Indonesia. Four unique globin chains (alpha A, alpha D, beta B, and beta C) were isolated in an equal molar ratio by high performance liquid chromatography from the hemolysate. The amino acid sequences of two alpha chains were determined. The alpha D chain has a glutamine at E7 as does an alpha chain of a snake, Liophis miliaris, but the alpha A chain has a histidine at E7 like the majority of hemoglobins. Phylogenetic analyses of 19 globins including two alpha chains of Komodo dragon and ones from representative amniotes showed the following results: (1) The a chains of squamates (snakes and lizards), which have a glutamine at E7, are clustered with the embryonic alpha globin family, which typically includes the alpha D chain from birds; (2) birds form a sister group with other reptiles but not with mammals; (3) the genes for embryonic and adult types of alpha globins were possibly produced by duplication of the ancestral alpha gene before ancestral amniotes diverged, indicating that each of the present amniotes might carry descendants of the two types of alpha globin genes; (4) squamates first split off from the ancestor of other reptiles and birds.

  11. Extraction of plutonium(IV) by bis(2-ethylhexyl) sulfoxide: a novel branched-chain extractant (Preprint No. ST.23)

    International Nuclear Information System (INIS)

    Shukla, J.P.; Kedari, C.S.

    1989-01-01

    Di-n-alkyl sulfoxides offer certain distint advantages over other common extractants for use in actinides separation particularly in the presence of high radiation fields. Despite widespread interest in these extractants, practical applications of such sulfoxides in nuclear fuel reprocessing have been seriously hampered owing to their poor solubility in common aliphatic hydrocarbon diluents. Recently a promising new branched-chain sulfoxide extractant, bis( 2-ethylhexyl) sulfoxide (BESO) has been introduced as a novel extracting agent for uranium. It possesses almost all the advantages of other sulfoxides, but excels the rest in terms of its complete miscibility with dodecane and the highest Ksub(H) value reported for any sulfoxide. As a part of comprehensive program to explore its analytical usefulness, data concerning preliminary studies on the extraction of plutonium with BESO form nitric acid solutions are reported. (author)

  12. Effect of branched-chain fatty acids, 3-methylindole and 4-methylphenol on consumer sensory scores of grilled lamb meat.

    Science.gov (United States)

    Watkins, P J; Kearney, G; Rose, G; Allen, D; Ball, A J; Pethick, D W; Warner, R D

    2014-02-01

    Tenderness, flavour, overall liking and odour are important components of sheepmeat eating quality. Consumer assessment of these attributes has been made for carcasses from the Information Nucleus Flock (INF) of the Cooperative Research Centre for Sheep Industry Innovation. The concentrations of three branched chain fatty acids, 4-methyloctanoic (MOA), 4-ethyloctanoic (EOA) and 4-methylnonanoic acids (compounds related to 'mutton flavour' in cooked sheepmeat) and 3-methylindole and 4-methylphenol (compounds related to 'pastoral' flavour) were determined for 178 fat samples taken from INF carcasses. Statistical modelling revealed that both MOA and EOA impacted on the 'Like Smell' consumer sensory score of the cooked meat product (Plamb will improve consumer acceptance of the cooked product but other factors affecting the eating quality also need to be considered. Copyright © 2012 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Improvement in carrier mobility and photovoltaic performance through random distribution of segments of linear and branched side chains

    Energy Technology Data Exchange (ETDEWEB)

    Egbe, Daniel A.M.; Adam, Getachew; Pivrikas, Almantas; Ulbricht, Christoph; Ramil, Alberto M.; Sariciftci, Niyazi Serdar [Johannes Kepler Univ., Linz (AT). Linz Inst. for Organic Solar Cells (LIOS); Hoppe, Harald [Technische Univ. Ilmenau (Germany). Inst. of Physics and Inst. of Micro- and Nanotechnologies; Rathgeber, Silke [Mainz Univ. (Germany). Inst. of Physics

    2010-07-01

    The random distribution of segments of linear octyloxy side chains and of branched 2-ethylhexyloxy side chains, on the backbone of anthracene containing poly(p-phenylene-ethynylene)-alt-poly(p-phenylene-vinylene) (PPE-PPV) has resulted in a side chain based statistical copolymer, denoted AnE-PVstat, showing optimized features as compared to the well defined homologues AnE-PVaa, -ab, -ba and -bb, whose constitutional units are incorporated into its backbone. WAXS studies on AnE-P's demonstrate the highest degree of order at the self-assembly state of AnE-PVstat, which is confirmed by its highly structured thin film absorption band. Electric field independent charge carrier mobility ({mu}{sub hole}) for AnE-PVstat was demonstrated by CELIV and OFET measurements, both methods resulting in similar {mu}{sub hole} values of up to 5.43 x 10{sup -4} cm{sup 2}/Vs. Upon comparison, our results show that charge carrier mobility as measured by CELIV technique is predominantly an intrachain process and less an interchain one, which is in line with past photoconductivity results from PPE-PPV based materials. The present side chain distribution favors efficient solar cell active layer phase separation. As a result, a smaller amount of PC{sub 60}BM is needed to achieve relatively high energy conversion efficiencies above 3 %. The efficiency of {eta}{sub AM1.5} {approx} 3.8 % obtained for AnE-PVstat:PC{sub 60}BM blend is presently the state-of-art value for PPV-based materials. (orig.)

  14. Branched-chain fatty acids in the neonatal gut and estimated dietary intake in infancy and adulthood.

    Science.gov (United States)

    Ran-Ressler, Rinat R; Glahn, Raymond P; Bae, SangEun; Brenna, J Thomas

    2013-01-01

    Branched-chain fatty acids (BCFA) are primarily saturated fatty acids (FA) with a methyl branch, usually near the terminal methyl group. BCFA are abundant in bacteria, skin, and vernix caseosa but have seldom been studied with respect to human nutrition. They are constituents of the term newborn infant gut lumen, being swallowed as vernix particulate components of amniotic fluid in the last trimester of normal pregnancy. We recently showed that BCFA protect against necrotizing enterocolitis (NEC) in the rat pup model. Dietary BCFA at levels similar to those found in human vernix reduced NEC incidence by more than 50%, increased the abundance of BCFA-containing bacteria, and increased the expression of ileal anti-inflammatory IL-10. The few published reports of BCFA in human milk enable an estimate that breastfed infants consume 19 mg BCFA per 100 ml milk. Dietary BCFA consumption from milk fat and other ruminant products, the main sources of dietary BCFA, is more than 400 mg BCFA per day in adult Americans. This estimate exceeds by severalfold the average dietary intake of bioactive FA, such as docosahexaenoic acid. BCFA are bioactive, abundant but neglected components of the human food supply. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  15. Identification and quantification of even and odd chained 5-n alkylresorcinols, branched chain-alkylresorcinols and methylalkylresorcinols in Quinoa (Chenopodium quinoa).

    Science.gov (United States)

    Ross, Alastair B; Svelander, Cecilia; Karlsson, Göran; Savolainen, Otto I

    2017-04-01

    Quinoa is a pseudocereal grown in the Andean region of South America that is of increasing interest worldwide as an alternative staple food. We have detected a complex mixture of both odd- and even-alkyl chain alkylresorcinols (AR), branched-chain alkylresorcinols (bcAR) and methylalkylresorcinols (mAR) in ethyl acetate extracts of quinoa. We quantified the content of AR in 17 commercial samples of quinoa, and found that the mean±SD content of AR was 58±16μg/g, bcAR was 182±52μg/g, and mAR was 136±40μg/g. AR from quinoa could also be detected in plasma after eating quinoa, indicating that some of these unique AR could be used as biomarkers of quinoa intake in humans. Further work is required to understand the role of these ARs in the quinoa plant and whether any of the novel ARs may be of particular interest in human nutrition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Growth-Environment Dependent Modulation of Staphylococcus aureus Branched-Chain to Straight-Chain Fatty Acid Ratio and Incorporation of Unsaturated Fatty Acids.

    Science.gov (United States)

    Sen, Suranjana; Sirobhushanam, Sirisha; Johnson, Seth R; Song, Yang; Tefft, Ryan; Gatto, Craig; Wilkinson, Brian J

    2016-01-01

    The fatty acid composition of membrane glycerolipids is a major determinant of Staphylococcus aureus membrane biophysical properties that impacts key factors in cell physiology including susceptibility to membrane active antimicrobials, pathogenesis, and response to environmental stress. The fatty acids of S. aureus are considered to be a mixture of branched-chain fatty acids (BCFAs), which increase membrane fluidity, and straight-chain fatty acids (SCFAs) that decrease it. The balance of BCFAs and SCFAs in USA300 strain JE2 and strain SH1000 was affected considerably by differences in the conventional laboratory medium in which the strains were grown with media such as Mueller-Hinton broth and Luria broth resulting in high BCFAs and low SCFAs, whereas growth in Tryptic Soy Broth and Brain-Heart Infusion broth led to reduction in BCFAs and an increase in SCFAs. Straight-chain unsaturated fatty acids (SCUFAs) were not detected. However, when S. aureus was grown ex vivo in serum, the fatty acid composition was radically different with SCUFAs, which increase membrane fluidity, making up a substantial proportion of the total (37%) and BCFAs (>36%) making up the rest. Staphyloxanthin, an additional major membrane lipid component unique to S. aureus, tended to be greater in content in cells with high BCFAs or SCUFAs. Cells with high staphyloxanthin content had a lower membrane fluidity that was attributed to increased production of staphyloxanthin. S. aureus saves energy and carbon by utilizing host fatty acids for part of its total fatty acids when growing in serum, which may impact biophysical properties and pathogenesis given the role of SCUFAs in virulence. The nutritional environment in which S. aureus is grown in vitro or in vivo in an infection is likely to be a major determinant of membrane fatty acid composition.

  17. Branched DNA nanostructures efficiently stabilised and monitored by novel pyrene-perylene 2'-α-l-amino-LNA FRET pairs

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Santhosh Kumar, T; Campbell, Meghan A

    2013-01-01

    Novel pyrene-perylene α-l-LNA FRET pairs described herein effectively detect assembly of 2- and 3-way branched DNA nanostructures prepared by postsynthetic microwave-assisted CuAAC click chemistry. The fluorescent signalling of assembly by internally positioned FRET pairs is achieved with low...

  18. Free amino acids in the sera of Boer goat bucks: a study under two ...

    African Journals Online (AJOL)

    .

    plasma concentrations of glycine (Gly), serine (Ser), aspartic acid (Asp), glutamic acid (Glu), .... a,b,c,d Values with different superscripts within the same row differ ... Branched-chain amino acids (derived from muscle protein catabolism) would ...

  19. Role of Chain Microstructure and Branching on Solution and Thin Film Phase Behavior

    Science.gov (United States)

    2015-11-30

    Chain Microstructure on Organization of Flexible/Semiflexible Block Copolymers  The choice of 1,3‐cyclohexadiene as the tailorable monomer was  motivated ...0.46:1  PS4  – PI4  60k‐60k   62.9k‐74.8k  1.07  0.457  0.840:1    60k‐120k   62.9k‐116.8k  1.06  0.350  0.54:1    ARO Final Report (PI: M. Kilbey)    5...nominal composition).  PS-PI PS2-PI2 PS4 -PI4 S/I=1 S/I=0.5 ARO Final Report (PI: M. Kilbey)    6    the PS/PVP interface, or possibly bury themselves

  20. Distribution of the branched-chain α-ketoacid dehydrogenase complex E1α subunit and glutamate dehydrogenase in the human brain and their role in neuro-metabolism.

    Science.gov (United States)

    Hull, Jonathon; Usmari Moraes, Marcela; Brookes, Emma; Love, Seth; Conway, Myra E

    2018-01-01

    Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised. We have used specific antibodies to these proteins to analyse their distribution within the human brain and report, for the first time, that the E1α subunit of the BCKD is located in both neurons and vascular endothelial cells. We also demonstrate that GDH is localised to astrocytes, although vascular immunolabelling does occur. The labelling of GDH was most intense in astrocytes adjacent to the hippocampus, in keeping with glutamatergic neurotransmission in this region. GDH was also present in astrocyte processes abutting vascular endothelial cells. Previously, we demonstrated that the branched-chain aminotransferase (hBCAT) proteins were most abundant in vascular cells (hBCATm) and neurons (hBCATc). Present findings are further evidence that BCAAs are metabolised within both the vasculature and neurons in the human brain. We suggest that GDH, hBCAT and the BCKD proteins operate in conjunction with astrocytic glutamate transporters and glutamine synthetase to regulate the availability of glutamate. This has important implications given that the dysregulation of glutamate metabolism, leading to glutamate excitotoxicity, is an important contributor to the pathogenesis of several neurodegenerative conditions such as Alzheimer's disease. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  1. Bio-based phenolic-branched-chain fatty acid isomers synthesized from vegetable oils and natural monophenols using modified h+-ferrierite zeolite

    Science.gov (United States)

    A new group of phenolic branched-chain fatty acids (n-PBC-FA), hybrid molecules of natural monophenols (i.e., thymol, carvacrol and creosote) and mixed fatty acid (i.e., derived from soybean and safflower oils), were efficiently produced through a process known as arylation. The reaction involves a...

  2. The influence of the side-chain sequence on the structure-activity correlations of immunomodulatory branched polypeptides. Synthesis and conformational analysis of new model polypeptides.

    Science.gov (United States)

    Mezö, G; Hudecz, F; Kajtár, J; Szókán, G; Szekerke, M

    1989-10-01

    New branched polypeptides were synthesized for a detailed study of the influence of the side-chain structure on the conformation and biological properties. The first subset of polypeptides were prepared by coupling of tetrapeptides to poly[L-Lys]. These polymers contain either DL-Ala3-X [poly[Lys-(X-DL-Ala3)n

  3. Equivalent chain lengths of all C4-C23 saturated monomethyl branched fatty acid methyl esters on methylsilicone OV-1 stationary phase.

    Science.gov (United States)

    Kubinec, Róbert; Blaško, Jaroslav; Górová, Renáta; Addová, Gabriela; Ostrovský, Ivan; Amann, Anton; Soják, Ladislav

    2011-04-01

    Isomer mixtures of monomethyl branched saturated C7-C23 fatty acid methyl esters (FAME) were prepared by performing a methylene insertion reaction to the straight chain FAME and this study model was completed by using commercially available standards of C4-C7 FAME. The equivalent chain lengths (ECL) of all 220 C4-C23 monomethyl branched FAME on OV-1 stationary phase were measured, achieving an average repeatability of ±0.0004 ECL units. The monomethyl branched FAME was identified by GC on the basis of regularity of the fractional chain lengths (FCL) dependence on the number of carbon atoms (C(z)) of individual homologous series of methyl 2-, 3-, …, 21-FAME. The prediction of retention of the first homologues, having the new position of methyl group beginning at higher carbon atoms number, and analogously for the second, third, fourth, and other members of the homologous series, allowed the dependence FCL=f(C(z)) for the first and subsequent members of beginning homologous of monomethyl derivatives of FAME. The identification was confirmed by mass spectrometry. All of the methyl isomers of FAME, which could not be completely separated by gas chromatography due to having a methyl group in surroundings of the middle of the carbon chain, were resolved by mass spectrometry using deconvolution in a SIM-mode. Measured gas chromatographic and mass spectrometric data were applied for identification of the monomethyl branched saturated FAME in tongue coating. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Utilization of milk amino acids for body gain in suckling mink (Mustela vison) kits

    DEFF Research Database (Denmark)

    Tauson, Anne-Helene; Fink, Rikke; Hansen, Niels E

    2005-01-01

    The efficiency of utilization of milk amino acids for body gain in suckling mink kits from small (n = 3), medium (n = 6) and large litters (n = 9) was investigated by using 36 mink dams and their litters for measurements during lactation weeks 1 through 4. Measurements on each dam and litter were...... performed once, hence three dams per litter size each week (n = 9). Individual milk intake of kits was determined, milk samples were collected and kits were killed for determination of amino acid composition. The most abundant amino acids in milk were glutamate, leucine and aspartate making up about 40......% of total amino acids. Branched chained amino acids made up slightly more than 20% and sulphur containing amino acids less than 5% of total milk amino acids. In kit bodies the sum of glutamate, aspartate and leucine made up about 32% of amino acids, branched chain amino acids about 16% and sulphur...

  5. Evaluation of the Branched-Chain DNA Assay for Measurement of RNA in Formalin-Fixed Tissues

    Science.gov (United States)

    Knudsen, Beatrice S.; Allen, April N.; McLerran, Dale F.; Vessella, Robert L.; Karademos, Jonathan; Davies, Joan E.; Maqsodi, Botoul; McMaster, Gary K.; Kristal, Alan R.

    2008-01-01

    We evaluated the branched-chain DNA (bDNA) assay QuantiGene Reagent System to measure RNA in formalin-fixed, paraffin-embedded (FFPE) tissues. The QuantiGene Reagent System does not require RNA isolation, avoids enzymatic preamplification, and has a simple workflow. Five selected genes were measured by bDNA assay; quantitative polymerase chain reaction (qPCR) was used as a reference method. Mixed-effect statistical models were used to partition the overall variance into components attributable to xenograft, sample, and assay. For FFPE tissues, the coefficients of reliability were significantly higher for the bDNA assay (93–100%) than for qPCR (82.4–95%). Correlations between qPCRFROZEN, the gold standard, and bDNAFFPE ranged from 0.60 to 0.94, similar to those from qPCRFROZEN and qPCRFFPE. Additionally, the sensitivity of the bDNA assay in tissue homogenates was 10-fold higher than in purified RNA. In 9- to 13-year-old blocks with poor RNA quality, the bDNA assay allowed the correct identification of the overexpression of known cancer genes. In conclusion, the QuantiGene Reagent System is considerably more reliable, reproducible, and sensitive than qPCR, providing an alternative method for the measurement of gene expression in FFPE tissues. It also appears to be well suited for the clinical analysis of FFPE tissues with diagnostic or prognostic gene expression biomarker panels for use in patient treatment and management. PMID:18276773

  6. The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen

    Directory of Open Access Journals (Sweden)

    Keyuan Liu

    2017-11-01

    Full Text Available Objective This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. Methods To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C. The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. Results The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05. The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05. The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. Conclusion This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter.

  7. Identification of In-Chain-Functionalized Compounds and Methyl-Branched Alkanes in Cuticular Waxes of Triticum aestivum cv. Bethlehem.

    Directory of Open Access Journals (Sweden)

    Radu C Racovita

    Full Text Available In this work, cuticular waxes from flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem were investigated in search for novel wax compounds. Seven wax compound classes were detected that had previously not been reported, and their structures were elucidated using gas chromatography-mass spectrometry of various derivatives. Six of the classes were identified as series of homologs differing by two methylene units, while the seventh was a homologous series with homologs with single methylene unit differences. In the waxes of flag leaf blades, secondary alcohols (predominantly C27 and C33, primary/secondary diols (predominantly C28 and esters of primary/secondary diols (predominantly C50, combining C28 diol with C22 acid were found, all sharing similar secondary hydroxyl group positions at and around C-12 or ω-12. 7- and 8-hydroxy-2-alkanol esters (predominantly C35, 7- and 8-oxo-2-alkanol esters (predominantly C35, and 4-alkylbutan-4-olides (predominantly C28 were found both in flag leaf and peduncle wax mixtures. Finally, a series of even- and odd-numbered alkane homologs was identified in both leaf and peduncle waxes, with an internal methyl branch preferentially on C-11 and C-13 of homologs with even total carbon number and on C-12 of odd-numbered homologs. Biosynthetic pathways are suggested for all compounds, based on common structural features and matching chain length profiles with other wheat wax compound classes.

  8. Electrochemical Branched-DNA Assay for Polymerase Chain Reaction-Free Detection and Quantification of Oncogenes in Messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ai Cheng; Dai, Ziyu; Chen, Baowei; Wu, Hong; Wang, Jun; Zhang, Aiguo; Zhang, Lurong; Lim, Tit-Meng; Lin, Yuehe

    2008-12-01

    We describe a novel electrochemical branched-DNA (bDNA) assay for polymerase chain reaction (PCR)-free detection and quantification of p185 BCR-ABL leukemia fusion transcript in the population of messenger RNA (mRNA) extracted from cell lines. The bDNA amplifier carrying high loading of alkaline phosphatase (ALP) tracers was used to amplify targets signal. The targets were captured on microplate well surfaces through cooperative sandwich hybridization prior to the labeling of bDNA. The activity of captured ALP was monitored by square-wave voltammetric (SWV) analysis of the electroactive enzymatic product in the presence of 1-napthyl-phosphate. The specificity and sensitivity of assay enabled direct detection of target transcript in as little as 4.6 ng mRNA without PCR amplification. In combination with the use of a well-quantified standard, the electrochemical bDNA assay was capable of direct use for a PCR-free quantitative analysis of target transcript in total mRNA population. The approach thus provides a simple, sensitive, accurate and quantitative tool alternate to the RQ-PCR for early disease diagnosis.

  9. The effect of the head group on branched-alkyl chain surfactants in glycolipid/n-octane/water ternary system.

    Science.gov (United States)

    Nainggolan, Irwana; Radiman, Shahidan; Hamzah, Ahmad Sazali; Hashim, Rauzah

    2009-10-01

    Two novel glycolipids have been synthesized and their phase behaviour studied. They have been characterized using FT-IR, FAB and 13C NMR and 1H NMR to ensure the purity of novel glycolipids. The two glycolipids are distinguished based on the head group of glycolipids (monosaccharide/glucose and disaccharide/maltose). These two novel glycolipids have been used as surfactant to perform two phase diagrams. Phase behaviours that have been investigated are 2-hexyldecyl-beta-D-glucopyranoside (2-HDG)/n-octane/water ternary system and 2-hexyldecyl-beta-D-maltoside (2-HDM)/n-octane/water ternary system. SAXS and polarizing optical microscope have been used to study the phase behaviours of these two surfactants in ternary phase diagram. Study of effect of the head group on branched-alkyl chain surfactants in ternary system is a strategy to derive the structure-property relationship. For comparison, 2-HDM and 2-HDG have been used as surfactant in the same ternary system. The phase diagram of 2-hexyldecyl-beta-D-maltoside/n-octane/water ternary system exhibited a Lalpha phase at a higher concentration regime, followed with two phases and a micellar solution region in a lower concentration regime. The phase diagram of 2-HDG/water/n-octane ternary system shows hexagonal phase, cubic phase, rectangular ribbon phase, lamellar phase, cubic phase as the surfactant concentration increase.

  10. The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen.

    Science.gov (United States)

    Liu, Keyuan; Hao, Xiaoyan; Li, Yang; Luo, Guobin; Zhang, Yonggen; Xin, Hangshu

    2017-11-01

    This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs) and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C). The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (pacids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (pacid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter.

  11. Site-specific antibodies distinguish single amino acid substitutions in position 57 in HLA-DQ beta-chain alleles associated with insulin-dependent diabetes

    DEFF Research Database (Denmark)

    Atar, D; Dyrberg, T; Michelsen, Birgitte

    1989-01-01

    The HLA-DQ beta-chain gene shows a close association with susceptibility or resistance to autoimmune insulin-dependent diabetes mellitus (IDDM) and it has been suggested that the amino acid in position 57 may be of pathogenetic importance. To study the expression of the IDDM associated HLA-DQ beta......-chain alleles, we immunized rabbits with 12 to 13 amino acid long peptides representing HLA-DQw7 and -DQw8 allelic sequences, differing only by one amino acid in position 57 being aspartic acid (Asp) and alanine (Ala), respectively. Immunoblot analysis of lymphoblastoid cells showed that several antisera...

  12. Synthesis and conformational analysis of linear homo- and heterooligomers from novel 2-C-branched sugar amino acids (SAAs).

    Science.gov (United States)

    Tian, Guang-Zong; Hu, Jing; Zhang, Heng-Xi; Rademacher, Christoph; Zou, Xiao-Peng; Zheng, Hong-Ning; Xu, Fei; Wang, Xiao-Li; Linker, Torsten; Yin, Jian

    2018-04-26

    Sugar amino acids (SAAs), as biologically interesting structures bearing both amino and carboxylic acid functional groups represent an important class of multifunctional building blocks. In this study, we develop an easy access to novel SAAs in only three steps starting from nitro compounds in high yields in analytically pure form, easily available by ceric (IV) mediated radical additions. Such novel SAAs have been applied in the assembly of total nine carbopeptoids with the form of linear homo- and heterooligomers for the structural investigations employing circular dichroism (CD) spectroscopy, which suggest that the carbopeptoids emerge a well-extended, left (or right)-handed conformation similar to polyproline II (PPII) helices. NMR studies also clearly demonstrated the presence of ordered secondary structural elements. 2D-ROESY spectra were acquired to identify i+1 NH ↔  i C 1 H, i C 2 H correlations which support the conformational analysis of tetramers by CD spectroscopy. These findings provide interesting information of SAAs and their oligomers as potential scaffolds for discovering new drugs and materials.

  13. Isolation of amino acid activating subunit-pantetheine protein complexes: Their role in chain elongation in tyrocidine synthesis

    Science.gov (United States)

    Lee, Sung G.; Lipmann, Fritz

    1977-01-01

    Dissociation of the multienzymes of tyrocidine synthesis by prolonged incubation of crude extracts of Bacillus brevis (Dubos strain, ATCC 8185) has yielded, on Sephadex G-100 chromatography, two fractions of amino acid activating subunits, a larger one of 70,000 daltons and a smaller one of 90,000 daltons; the latter was a complex consisting of the 70,000 dalton subunit and the pantetheine-carrying protein of about 20,000 daltons. When it dissociated, the intermediate enzyme, which activates three amino acids, contained two-thirds of the subunits in the 70,000 dalton and one-third in the 90,000 dalton fraction; the heavy enzyme, which activates six amino acids, contained five-sixths of the subunits in the former fraction and one-sixth in the latter. Both fractions showed ATP-PPi exchange with all amino acids that are activated by the respective polyenzymes. With proline as an example, the 70,000 dalton subunit exhibited a single low-affinity binding site, which should correspond to the peripheral thiol acceptor site, whereas the 90,000 dalton subunit showed both a low-affinity binding site and an additional high-affinity site for proline; the high-affinity site is attributed to the pantetheine present on the pantetheine-carrying protein, and suggests that amino acids are translocated from the peripheral SH to the pantetheine-carrying moiety during chain elongation. This was confirmed by the observation that the 90,000 dalton complex, when incubated with the light enzyme in the presence of phenylalanine and proline, produced DPhe-Pro dipeptide that cyclized into DPhe-Pro diketopiperazine, but the 70,000 dalton activating subunit, when similarly incubated, did not. After subunit dissociation, however, no further elongation occurred after the transfer from phenylalanine to proline. Images PMID:196286

  14. INVERSION SYMMETRY, ARCHITECTURE AND DISPERSITY, AND THEIR EFFECTS ON THERMODYNAMICS IN BULK AND CONFINED REGIONS: FROM RANDOMLY BRANCHED POLYMERS TO LINEAR CHAINS, STARS AND DENDRIMERS

    Directory of Open Access Journals (Sweden)

    P.D.Gujrati

    2002-01-01

    Full Text Available Theoretical evidence is presented in this review that architectural aspects can play an important role, not only in the bulk but also in confined geometries by using our recursive lattice theory, which is equally applicable to fixed architectures (regularly branched polymers, stars, dendrimers, brushes, linear chains, etc. and variable architectures, i.e. randomly branched structures. Linear chains possess an inversion symmetry (IS of a magnetic system (see text, whose presence or absence determines the bulk phase diagram. Fixed architectures possess the IS and yield a standard bulk phase diagram in which there exists a theta point at which two critical lines C and C' meet and the second virial coefficient A2 vanishes. The critical line C appears only for infinitely large polymers, and an order parameter is identified for this criticality. The critical line C' exists for polymers of all sizes and represents phase separation criticality. Variable architectures, which do not possess the IS, give rise to a topologically different phase diagram with no theta point in general. In confined regions next to surfaces, it is not the IS but branching and monodispersity, which becomes important in the surface regions. We show that branching plays no important role for polydisperse systems, but become important for monodisperse systems. Stars and linear chains behave differently near a surface.

  15. Alanine scan of the peptide antibiotic feglymycin: assessment of amino acid side chains contributing to antimicrobial activity.

    Science.gov (United States)

    Hänchen, Anne; Rausch, Saskia; Landmann, Benjamin; Toti, Luigi; Nusser, Antje; Süssmuth, Roderich D

    2013-03-18

    The antibiotic feglymycin is a linear 13-mer peptide synthesized by the bacterium Streptomyces sp. DSM 11171. It mainly consists of the nonproteinogenic amino acids 4-hydroxyphenylglycine and 3,5-dihydroxyphenylglycine. An alanine scan of feglymycin was performed by solution-phase peptide synthesis in order to assess the significance of individual amino acid side chains for biological activity. Hence, 13 peptides were synthesized from di- and tripeptide building blocks, and subsequently tested for antibacterial activity against Staphylococcus aureus strains. Furthermore we tested the inhibition of peptidoglycan biosynthesis enzymes MurA and MurC, which are inhibited by feglymycin. Whereas the antibacterial activity is significantly based on the three amino acids D-Hpg1, L-Hpg5, and L-Phe12, the inhibitory activity against MurA and MurC depends mainly on L-Asp13. The difference in the position dependence for antibacterial activity and enzyme inhibition suggests multiple molecular targets in the modes of action of feglymycin. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Bifurcation and extinction limit of stretched premixed flames with chain-branching intermediate kinetics and radiative loss

    Science.gov (United States)

    Zhang, Huangwei; Chen, Zheng

    2018-05-01

    Premixed counterflow flames with thermally sensitive intermediate kinetics and radiation heat loss are analysed within the framework of large activation energy. Unlike previous studies considering one-step global reaction, two-step chemistry consisting of a chain branching reaction and a recombination reaction is considered here. The correlation between the flame front location and stretch rate is derived. Based on this correlation, the extinction limit and bifurcation characteristics of the strained premixed flame are studied, and the effects of fuel and radical Lewis numbers as well as radiation heat loss are examined. Different flame regimes and their extinction characteristics can be predicted by the present theory. It is found that fuel Lewis number affects the flame bifurcation qualitatively and quantitatively, whereas radical Lewis number only has a quantitative influence. Stretch rates at the stretch and radiation extinction limits respectively decrease and increase with fuel Lewis number before the flammability limit is reached, while the radical Lewis number shows the opposite tendency. In addition, the relation between the standard flammability limit and the limit derived from the strained near stagnation flame is affected by the fuel Lewis number, but not by the radical Lewis number. Meanwhile, the flammability limit increases with decreased fuel Lewis number, but with increased radical Lewis number. Radical behaviours at flame front corresponding to flame bifurcation and extinction are also analysed in this work. It is shown that radical concentration at the flame front, under extinction stretch rate condition, increases with radical Lewis number but decreases with fuel Lewis number. It decreases with increased radiation loss.

  17. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review

    Science.gov (United States)

    2016-01-01

    Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic patients. However, results seem to be controversial in different races, diets, and distinct tissues. Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies. We performed systematic review, searching MEDLINE, EMASE, ClinicalTrials.gov, the Cochrane Library, and Web of Science from inception to March 2016. After selection, 23 studies including 20,091 participants were included. Based on current evidence, we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk. Factors influencing BCAA level can be divided into four parts: race, gender, dietary patterns, and gene variants. These factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance. Genes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders. Moreover, these factors should be controlled properly during study design and data analysis. In the future, more large-scale studies with elaborate design addressing BCAA and IR are required. PMID:27642608

  18. Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution

    Directory of Open Access Journals (Sweden)

    Adriano Maida

    2017-08-01

    Conclusions: Repletion of BCAAs in dietary PD is sufficient to oppose changes in somatic mTORC1 signaling but does not reverse the hepatic ISR nor induce insulin resistance in type 2 diabetes during dietary PD.

  19. The influence of environmental parameters on the catabolism of branched-chain amino acids by Staphylococcus xylosus and Staphylococcus carnosus

    DEFF Research Database (Denmark)

    Olesen, Pelle Thonning; Stahnke, Louise Heller

    2004-01-01

    . The environmental conditions studied were temperature (12-28degreesC), NaCl concentration (4.0-12.0% (w/w)) acidity (pH 4.8-5.8) and addition of manganese (0-2.5mg Mn/kg). Flavour compounds were sampled by automatic static headspace collection and separated/quantified using gas chromatography/flame ionization...

  20. The influence of precultivation parameters on the catabolism of branched-chain amino acids by Staphylococcus xylosus and Staphylococcus carnosus

    DEFF Research Database (Denmark)

    Olesen, Pelle Thonning; Stahnke, Louise Heller

    2003-01-01

    precultivation parameters were: growth phase, temperature, NaCl concentration and the concentration of leucine, isoleucine and valine (only for S. xylosus). Flavour compounds were sampled by automatic static headspace collection and separated/quantified using gas chromatography/flame ionization detection (GC...

  1. Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels

    DEFF Research Database (Denmark)

    Engelbrechtsen, Line; Iepsen, Eva Pers Winning; Galijatovic, Ehm Astrid Andersson

    2016-01-01

    increased during weight loss (p = 5.2 × 10−15) and showed inverse correlation with insulin resistance measured by HOMA–IR levels (r = −0.318, p = 0.025). Valine concentrations were lower in the control group compared to the GLP-1RA group during weight maintenance (p = 0.005). Conclusion Weight loss...

  2. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Xue Zhao

    2016-01-01

    Full Text Available Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine and insulin resistance (IR in obese or diabetic patients. However, results seem to be controversial in different races, diets, and distinct tissues. Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies. We performed systematic review, searching MEDLINE, EMASE, ClinicalTrials.gov, the Cochrane Library, and Web of Science from inception to March 2016. After selection, 23 studies including 20,091 participants were included. Based on current evidence, we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk. Factors influencing BCAA level can be divided into four parts: race, gender, dietary patterns, and gene variants. These factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance. Genes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders. Moreover, these factors should be controlled properly during study design and data analysis. In the future, more large-scale studies with elaborate design addressing BCAA and IR are required.

  3. Anesthesia and bariatric surgery gut preparation alter plasma acylcarnitines reflective of mitochondrial fat and branched-chain amino acid oxidation

    Science.gov (United States)

    The period around bariatric surgery offers a unique opportunity to characterize metabolism responds to dynamic shifts in energy, gut function, and anesthesia. We analyzed plasma acylcarnitines in obese women (n=17) sampled in the overnight fasted/postabsorptive state ca. 1-2 weeks prior to surgery ...

  4. Bis(thienothiophenyl) diketopyrrolopyrrole-based conjugated polymers with various branched alkyl side chains and their applications in thin-film transistors and polymer solar cells.

    Science.gov (United States)

    Shin, Jicheol; Park, Gi Eun; Lee, Dae Hee; Um, Hyun Ah; Lee, Tae Wan; Cho, Min Ju; Choi, Dong Hoon

    2015-02-11

    New thienothiophene-flanked diketopyrrolopyrrole and thiophene-containing π-extended conjugated polymers with various branched alkyl side-chains were successfully synthesized. 2-Octyldodecyl, 2-decyltetradecyl, 2-tetradecylhexadecyl, 2-hexadecyloctadecyl, and 2-octadecyldocosyl groups were selected as the side-chain moieties and were anchored to the N-positions of the thienothiophene-flanked diketopyrrolopyrrole unit. All five polymers were found to be soluble owing to the bulkiness of the side chains. The thin-film transistor based on the 2-tetradecylhexadecyl-substituted polymer showed the highest hole mobility of 1.92 cm2 V(-1) s(-1) due to it having the smallest π-π stacking distance between the polymer chains, which was determined by grazing incidence X-ray diffraction. Bulk heterojunction polymer solar cells incorporating [6,6]-phenyl-C71-butyric acid methyl ester as the n-type molecule and the additive 1,8-diiodooctane (1 vol %) were also constructed from the synthesized polymers without thermal annealing; the device containing the 2-octyldodecyl-substituted polymer exhibited the highest power conversion efficiency of 5.8%. Although all the polymers showed similar physical properties, their device performance was clearly influenced by the sizes of the branched alkyl side-chain groups.

  5. Structural characterization of saturated branched chain fatty acid methyl esters by collisional dissociation of molecular ions generated by electron ionization[S

    Science.gov (United States)

    Ran-Ressler, Rinat R.; Lawrence, Peter; Brenna, J. Thomas

    2012-01-01

    Saturated branched chain fatty acids (BCFA) are present as complex mixtures in numerous biological samples. The traditional method for structure elucidation, electron ionization (EI) mass spectrometry, sometimes does not unambiguously enable assignment of branching in isomeric BCFA. Zirrolli and Murphy (Zirrolli , J. A. , and R. A. Murphy. 1993. Low-energy tandem mass spectrometry of the molecular ion derived from fatty acid methyl esters: a novel method for analysis of branched-chain fatty acids. J. Am. Soc. Mass Spectrom. 4: 223–229.) showed that the molecular ions of four BCFA methyl ester (BCFAME) yield highly characteristic fragments upon collisional dissociation using a triple quadrupole instrument. Here, we confirm and extend these results by analysis using a tabletop 3-D ion trap for activated molecular ion EI-MS/MS to 30 BCFAME. iso-BCFAME produces a prominent ion (30-100% of base peak) for [M-43] (M-C3H7), corresponding to the terminal isopropyl moiety in the original iso-BCFAME. Anteiso-FAME yield prominent ions (20-100% of base peak) corresponding to losses on both side of the methyl branch, [M-29] and [M-57], and tend to produce more prominent m/z 115 peaks corresponding to a cyclization product around the ester. Dimethyl and tetramethyl FAME, with branches separated by at least one methylene group, yield fragment on both sides of the sites of methyl branches that are more than 6 C away from the carboxyl carbon. EI-MS/MS yields uniquely specific ions that enable highly confident structural identification and quantification of BCFAME. PMID:22021637

  6. Excess molar volumes of (an alkanol plus a branched chain ether) at the temperature 298.15 K and the application of the ERAS model

    CSIR Research Space (South Africa)

    Letcher, TM

    1997-12-01

    Full Text Available Phase Equilibria 140 (1997) 207-220 The excess molar the temperature volumes of (an alkanol + a branched chain ether) at 298.15 K and the application of the ERAS model Trevor M. Letcher * , Penny U. Govender ? Drpartnwnt... V,,? results presented here, together with the previously reported data for the molar excess enthalpy Hi, has been used to test the Extended Real Associated Solution (ERAS) model. 0 1997 Elsevier Science B.V. Ke...

  7. Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping

    DEFF Research Database (Denmark)

    Madsen, Pia Pinholt

    2006-01-01

    Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of L: -isoleucine catabolism. Little is known about the clinical presentation associated with this enzyme defect, as it has been reported in only a limited number of patients. Because the presence...... is relevant to the interpretation of the functional consequences of this type of mutation in other disease genes....

  8. Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues.

    Science.gov (United States)

    Peng, Tao; Huang, Bingzhen; Sun, Yao; Lu, Yongbo; Bonewald, Lynda; Chen, Shuo; Butler, William T; Feng, Jerry Q; D'Souza, Rena N; Qin, Chunlin

    2009-01-01

    Dentin matrix protein 1 (DMP1) is present in the extracellular matrix (ECM) of dentin and bone as processed NH(2)- and COOH-terminal fragments, resulting from proteolytic cleavage at the NH(2) termini of 4 aspartic acid residues during rat DMP1 processing. One cleavage site residue, Asp(181) (corresponding to Asp(197) of mouse DMP1), and its flanking region are highly conserved across species. We speculate that cleavage at the NH(2) terminus of Asp(197) of mouse DMP1 represents an initial, first-step scission in the whole cascade of proteolytic processing. To test if Asp(197) is critical for initiating the proteolytic processing of mouse DMP1, we substituted Asp(197) with Ala(197) by mutating the corresponding nucleotides of mouse cDNA that encode this amino acid residue. This mutant DMP1 cDNA was cloned into a pcDNA3.1 vector. Data from transfection experiments indicated that this single substitution blocked the proteolytic processing of mouse DMP1 in HEK-293 cells, indicating that cleavage at the NH(2) terminus of Asp(197) is essential for exposing other cleavage sites for the conversion of DMP1 to its fragments. The NH(2)-terminal fragment of DMP1 occurs as a proteoglycan form (DMP1-PG) that contains a glycosaminoglycan (GAG) chain. Previously, we showed that a GAG chain is linked to Ser(74) in rat DMP1 (Ser(89) in mouse DMP1). To confirm that mouse DMP1-PG possesses a single GAG chain attached to Ser(89), we substituted Ser(89) by Gly(89). Data from transfection analysis indicated that this substitution completely prevented formation of the GAG-containing form, confirming that DMP1-PG contains a single GAG chain attached to Ser(89) in mouse DMP1. Copyright 2008 S. Karger AG, Basel.

  9. Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans

    DEFF Research Database (Denmark)

    Berg, Ronan Mg; Taudorf, Sarah; Bailey, Damian M

    2010-01-01

    Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along...

  10. Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans

    DEFF Research Database (Denmark)

    Berg, Ronan Mg; Taudorf, Sarah; Bailey, Damian M

    2010-01-01

    Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a ...

  11. Determination of rate constants and branching ratios for TCE degradation by zero-valent iron using a chain decay multispecies model.

    Science.gov (United States)

    Hwang, Hyoun-Tae; Jeen, Sung-Wook; Sudicky, Edward A; Illman, Walter A

    2015-01-01

    The applicability of a newly-developed chain-decay multispecies model (CMM) was validated by obtaining kinetic rate constants and branching ratios along the reaction pathways of trichloroethene (TCE) reduction by zero-valent iron (ZVI) from column experiments. Changes in rate constants and branching ratios for individual reactions for degradation products over time for two columns under different geochemical conditions were examined to provide ranges of those parameters expected over the long-term. As compared to the column receiving deionized water, the column receiving dissolved CaCO3 showed higher mean degradation rates for TCE and all of its degradation products. However, the column experienced faster reactivity loss toward TCE degradation due to precipitation of secondary carbonate minerals, as indicated by a higher value for the ratio of maximum to minimum TCE degradation rate observed over time. From the calculated branching ratios, it was found that TCE and cis-dichloroethene (cis-DCE) were dominantly dechlorinated to chloroacetylene and acetylene, respectively, through reductive elimination for both columns. The CMM model, validated by the column test data in this study, provides a convenient tool to determine simultaneously the critical design parameters for permeable reactive barriers and natural attenuation such as rate constants and branching ratios. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. The catalytic chain of human complement subcomponent C1r. Purification and N-terminal amino acid sequences of the major cyanogen bromide-cleavage fragments.

    Science.gov (United States)

    Arlaud, G J; Gagnon, J; Porter, R R

    1982-01-01

    1. The a- and b-chains of reduced and alkylated human complement subcomponent C1r were separated by high-pressure gel-permeation chromatography and isolated in good yield and in pure form. 2. CNBr cleavage of C1r b-chain yielded eight major peptides, which were purified by gel filtration and high-pressure reversed-phase chromatography. As determined from the sum of their amino acid compositions, these peptides accounted for a minimum molecular weight of 28 000, close to the value 29 100 calculated from the whole b-chain. 3. N-Terminal sequence determinations of C1r b-chain and its CNBr-cleavage peptides allowed the identification of about two-thirds of the amino acids of C1r b-chain. From our results, and on the basis of homology with other serine proteinases, an alignment of the eight CNBr-cleavage peptides from C1r b-chain is proposed. 4. The residues forming the 'charge-relay' system of the active site of serine proteinases (His-57, Asp-102 and Ser-195 in the chymotrypsinogen numbering) are found in the corresponding regions of C1r b-chain, and the amino acid sequence around these residues has been determined. 5. The N-terminal sequence of C1r b-chain has been extended to residue 60 and reveals that C1r b-chain lacks the 'histidine loop', a disulphide bond that is present in all other known serine proteinases.

  13. Regulatory effect of amino acids on the pasting behavior of potato starch is attributable to its binding to the starch chain.

    Science.gov (United States)

    Ito, Azusa; Hattori, Makoto; Yoshida, Tadashi; Watanabe, Ayako; Sato, Ryoichi; Takahashi, Koji

    2006-12-27

    The binding of an amino acid, glycine (Gly), alanine (Ala), epsilon-aminocaproic acid (-AC), monosodium glutamate (GluNa), or lysine (Lys), to starch was examined by a biomolecular interaction analyzer (IAsys). A starch sample (ATS) hydrolyzed to an extent of 1% hydrolysis rate with 15% sulfuric acid was used as a model starch for the binding examination. The reducing end of ATS was oxidized by the Somogyi reagent, and the conversion of the reducing end to the carboxyl group of ATS was confirmed by a carboxylic acid fluorescence labeling reagent. The oxidized ATS was immobilized to the amino group of a sensor cuvette by using water-soluble carbodiimide and N-hydroxysuccinimide through an amide bond. The IAsys examination showed that Gly, Ala, and epsilon-AC scarcely bound to the immobilized starch chains but that GluNa and Lys favorably bound with their increasing concentrations. The relative binding index (RBI) of each amino acid was defined by the ratio of the slope of the linear regression equation between the binding response and the concentration for each amino acid to that for Gly. Because the relationships between the RBI and the pasting characteristics (pasting temperature, peak viscosity, breakdown, and swelling index) could each be expressed by a linear regression equation with a high correlation coefficient, it is concluded that the regulation of the pasting behavior of starch with an amino acid is caused by binding of the amino acid to the starch chains.

  14. Analytic study of the chain dark decomposition reaction of iodides - atomic iodine donors - in the active medium of a pulsed chemical oxygen-iodine laser: 1. Criteria for the development of the branching chain dark decomposition reaction of iodides

    International Nuclear Information System (INIS)

    Andreeva, Tamara L; Kuznetsova, S V; Maslov, Aleksandr I; Sorokin, Vadim N

    2009-01-01

    The scheme of chemical processes proceeding in the active medium of a pulsed chemical oxygen-iodine laser (COIL) is analysed. Based on the analysis performed, the complete system of differential equations corresponding to this scheme is replaced by a simplified system of equations describing in dimensionless variables the chain dark decomposition of iodides - atomic iodine donors, in the COIL active medium. The procedure solving this system is described, the basic parameters determining the development of the chain reaction are found and its specific time intervals are determined. The initial stage of the reaction is analysed and criteria for the development of the branching chain decomposition reaction of iodide in the COIL active medium are determined. (active media)

  15. Effects of clofibric acid on the activity and activity state of the hepatic branched-chain 2-oxo acid dehydrogenase complex.

    OpenAIRE

    Zhao, Y; Jaskiewicz, J; Harris, R A

    1992-01-01

    Feeding clofibric acid to rats caused little or no change in total activity of the liver branched-chain 2-oxo acid dehydrogenase complex (BCODC). No change in mass of liver BCODC was detected by immunoblot analysis in response to dietary clofibric acid. No changes in abundance of mRNAs for the BCODC E1 alpha, E1 beta and E2 subunits were detected by Northern-blot analysis. Likewise, dietary clofibric acid had no effect on the activity state of liver BCODC (percentage of enzyme in the dephosph...

  16. Side-chain amino-acid-based pH-responsive self-assembled block copolymers for drug delivery and gene transfer.

    Science.gov (United States)

    Kumar, Sonu; Acharya, Rituparna; Chatterji, Urmi; De, Priyadarsi

    2013-12-10

    Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

  17. The Role of Microbial Amino Acid Metabolism in Host Metabolism

    Directory of Open Access Journals (Sweden)

    Evelien P. J. G. Neis

    2015-04-01

    Full Text Available Disruptions in gut microbiota composition and function are increasingly implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. The functional output of the gut microbiota, including short-chain fatty acids and amino acids, are thought to be important modulators underlying the development of these disorders. Gut bacteria can alter the bioavailability of amino acids by utilization of several amino acids originating from both alimentary and endogenous proteins. In turn, gut bacteria also provide amino acids to the host. This could have significant implications in the context of insulin resistance and type 2 diabetes mellitus, conditions associated with elevated systemic concentrations of certain amino acids, in particular the aromatic and branched-chain amino acids. Moreover, several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids, which also play a role in the development of obesity. In this review, we aim to compile the available evidence on the contribution of microbial amino acids to host amino acid homeostasis, and to assess the role of the gut microbiota as a determinant of amino acid and short-chain fatty acid perturbations in human obesity and type 2 diabetes mellitus.

  18. Solid-State Organization and Ambipolar Field-Effect Transistors of Benzothiadiazole-Cyclopentadithiophene Copolymer with Long Branched Alkyl Side Chains

    Directory of Open Access Journals (Sweden)

    Martin Baumgarten

    2013-06-01

    Full Text Available The solid-state organization of a benzothiadiazole-cyclopentadithiophene copolymer with long, branched decyl-tetradecyl side chains (CDT-BTZ-C14,10 is investigated. The C14,10 substituents are sterically demanding and increase the π-stacking distance to 0.40 nm from 0.37 nm for the same polymer with linear hexadecyls (C16. Despite the bulkiness, the C14,10 side chains tend to crystallize, leading to a small chain-to-chain distance between lamellae stacks and to a crystal-like microstructure in the thin film. Interestingly, field-effect transistors based on solution processed layers of CDT-BTZ-C14,10 show ambipolar behavior in contrast to CDT-BTZ-C16 with linear side chains, for which hole transport was previously observed. Due to the increased π-stacking distance, the mobilities are only 6 × 10−4 cm²/Vs for electrons and 6 × 10−5 cm²/Vs for holes, while CDT-BTZ-C16 leads to values up to 5.5 cm²/Vs. The ambipolarity is attributed to a lateral shift between stacked backbones provoked by the bulky C14,10 side chains. This reorganization is supposed to change the transfer integrals between the C16 and C14,10 substituted polymers. This work shows that the electronic behavior in devices of one single conjugated polymer (in this case CDT-BTZ can be controlled by the right choice of the substituents to place the backbones in the desired packing.

  19. A novel branched side-chain-type sulfonated polyimide membrane with flexible sulfoalkyl pendants and trifluoromethyl groups for vanadium redox flow batteries

    Science.gov (United States)

    Li, Jinchao; Liu, Suqin; He, Zhen; Zhou, Zhi

    2017-04-01

    A novel branched side-chain-type sulfonated polyimide (6F-s-bSPI) membrane with accessible branching agents of melamine, hydrophobic trifluoromethyl groups (sbnd CF3), and flexible sulfoalkyl pendants is prepared by a high-temperature polycondensation and post-sulfonation method for use in vanadium redox flow batteries (VRFBs). The chemical structure of the 6F-s-bSPI membrane is confirmed by ATR-FTIR and 1H NMR spectra. The physico-chemical properties of the as-prepared 6F-s-bSPI membrane are systematically investigated and found to be strongly related to the specially designed structure. The 6F-s-bSPI membrane offers a reduced cost and possesses a significantly lowered vanadium ion permeability (1.18 × 10-7 cm2 min-1) compared to the linear SPI (2.25 × 10-7 cm2 min-1) and commercial Nafion 115 (1.36 × 10-6 cm2 min-1) membranes, prolonging the self-discharge duration of the VRFBs. In addition, the VRFB assembled with a 6F-s-bSPI membrane shows higher coulombic (98.3%-99.7%) and energy efficiencies (88.4%-66.12%) than that with a SPI or Nafion 115 membrane under current densities ranging from 20 to 100 mA cm-2. Moreover, the VRFB with a 6F-s-bSPI membrane delivers a stable cycling performance over 100 cycles with no decline in coulombic and energy efficiencies. These results show that the branched side-chain-type structure is a promising design to prepare excellent proton conductive membranes.

  20. Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network.

    Science.gov (United States)

    Zhu, Chongqin; Gao, Yurui; Li, Hui; Meng, Sheng; Li, Lei; Francisco, Joseph S; Zeng, Xiao Cheng

    2016-11-15

    Hydrophobicity of macroscopic planar surface is conventionally characterized by the contact angle of water droplets. However, this engineering measurement cannot be directly extended to surfaces of proteins, due to the nanometer scale of amino acids and inherent nonplanar structures. To measure the hydrophobicity of side chains of proteins quantitatively, numerous parameters were developed to characterize behavior of hydrophobic solvation. However, consistency among these parameters is not always apparent. Herein, we demonstrate an alternative way of characterizing hydrophobicity of amino acid side chains in a protein environment by constructing a monolayer of amino acids (i.e., artificial planar peptide network) according to the primary and the β-sheet secondary structures of protein so that the conventional engineering measurement of the contact angle of a water droplet can be brought to bear. Using molecular dynamics simulations, contact angles θ of a water nanodroplet on the planar peptide network, together with excess chemical potentials of purely repulsive methane-sized Weeks-Chandler-Andersen solute, are computed. All of the 20 types of amino acids and the corresponding planar peptide networks are studied. Expectedly, all of the planar peptide networks with nonpolar amino acids are hydrophobic due to θ [Formula: see text] 90°, whereas all of the planar peptide networks of the polar and charged amino acids are hydrophilic due to θ [Formula: see text] 90°. Planar peptide networks of the charged amino acids exhibit complete-wetting behavior due to θ [Formula: see text] 0°. This computational approach for characterization of hydrophobicity can be extended to artificial planar networks of other soft matter.

  1. Amino Acid Functionalization of Doped Single-Walled Carbon Nanotubes: Effects of Dopants and Side Chains as Well as Zwitterionic Stabilizations.

    Science.gov (United States)

    Jiang, Lisha; Zhu, Chang; Fu, Yujie; Yang, Gang

    2017-04-06

    Functionalization of single-walled carbon nanotubes (SWCNTs) is necessitated in a number of conditions such as drug delivery, and here amino acid functionalization of SWCNTs is conducted within the framework of density functional theory. Functionalization efficiencies of Gly are largely determined by dopants, as a combined effect of atomic radius, electronic configuration, and distortion to SWCNTs. Different functionalization sites in Gly have divergent interaction strengths with M/SWCNTs that decline as O b > N > O a , and this trend seems almost independent of the identity of metallic dopants. B/SWCNT behaves distinctly and prefers to the N site. Dopants affect principally interaction strengths, while amino acids regulate significantly both functionalization configurations and interaction energies. Then focus is given to stabilization of zwitterionic amino acids due to enhanced interactions with the widely used zwitterionic drugs. All metallic dopants render zwitterionic Gly to be the most stable, and side chains in amino acids rather than dopants in M/SWCNTs cause more pronounced effects to zwitterionic stabilizations. Charge transfers between amino acids and M/SWCNTs are closely associated with zwitterionic stabilization effects, and different charge transfer mechanisms between M/SWCNTs and metal ions are interpreted. Thus, this work provides a comprehensive understanding of amino acid functionalization of M/SWCNTs.

  2. Highly crystalline films of PCPDTBT with branched side chains by solvent vapor crystallization: influence on opto-electronic properties.

    Science.gov (United States)

    Fischer, Florian S U; Trefz, Daniel; Back, Justus; Kayunkid, Navaphun; Tornow, Benjamin; Albrecht, Steve; Yager, Kevin G; Singh, Gurpreet; Karim, Alamgir; Neher, Dieter; Brinkmann, Martin; Ludwigs, Sabine

    2015-02-18

    PCPDTBT, a marginally crystallizable polymer, is crystallized into a new crystal structure using solvent-vapor annealing. Highly ordered areas with three different polymer-chain orientations are identified using TEM/ED, GIWAXS, and polarized Raman spectroscopy. The optical and structural properties differ significantly from films prepared by standard device preparation protocols. Bilayer solar cells, however, show similar performance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.

    OpenAIRE

    Dorman, J S; LaPorte, R E; Stone, R A; Trucco, M

    1990-01-01

    The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin-dependent diabetes mellitus (IDDM), whereas an aspartic acid at this position (Asp-57) appears to confer resistance to the disease. We hypothesize that the 30-fold difference in IDDM incidence across racial groups and countries is related to variability in the frequency of these alleles. Diabetic and nondiabetic individuals were evalua...

  4. A cyclam core dendrimer containing dansyl and oligoethylene glycol chains in the branches: protonation and metal coordination.

    Science.gov (United States)

    Branchi, Barbara; Ceroni, Paola; Bergamini, Giacomo; Balzani, Vincenzo; Maestri, Mauro; van Heyst, Jeroen; Lee, Sang-Kyu; Luppertz, Friedhelm; Vögtle, Fritz

    2006-12-04

    We have synthesized a dendrimer (1) consisting of a 1,4,8,11-tetraazacyclotetradecane (cyclam) core, appended with four benzyl substituents that carry, in the 3- and 5-positions, a dansyl amide derivative (of type 2), in which the amide hydrogen is replaced by a benzyl unit that carries an oligoethylene glycol chain in the 3- and 5-positions. All together, the dendrimer contains 16 potentially luminescent moieties (eight dansyl- and eight dimethoxybenzene-type units) and three distinct types of multivalent sites that, in principle, can be protonated or coordinated to metal ions (the cyclam nitrogen atoms, the amine moieties of the eight dansyl units, and the 16 oligoethylene glycol chains). We have studied the absorption and luminescence properties of 1, 2, and 3 in acetonitrile and the changes taking place upon titration with acid and a variety of divalent (Co2+, Ni2+, Cu2+, Zn2+), and trivalent (Nd3+, Eu3+, Gd3+) metal ions as triflate and/or nitrate salts. The results obtained show that: 1) double protonation of the cyclam ring takes place before protonation of the dansyl units; 2) the oligoethylene glycol chains do not interfere with protonation of the cyclam core and the dansyl units in the ground state, but affect the luminescence of the protonated dansyl units; 3) the first equivalent of metal ion is coordinated by the cyclam core; 4) the interaction of the resulting cyclam complex with the appended dansyl units depends on the nature of the metal ion; 5) coordination of metal ions by the dansyl units follows at high metal-ion concentrations; 6) the effect of the metal ion depends on the nature of the counterion. This example demonstrates that dendrimers may exhibit complete functionality resulting from the integration of the specific properties of their component units.

  5. Direct RNA detection without nucleic acid purification and PCR: Combining sandwich hybridization with signal amplification based on branched hybridization chain reaction.

    Science.gov (United States)

    Xu, Yao; Zheng, Zhi

    2016-05-15

    We have developed a convenient, robust and low-cost RNA detection system suitable for high-throughput applications. This system uses a highly specific sandwich hybridization to capture target RNA directly onto solid support, followed by on-site signal amplification via 2-dimensional, branched hybridizing chain polymerization through toehold-mediated strand displacement reaction. The assay uses SYBR Green to detect targets at concentrations as low as 1 pM, without involving nucleic acid purification or any enzymatic reaction, using ordinary oligonucleotides without modification or labeling. The system was demonstrated in the detection of malaria RNA in blood and GAPDH gene expression in cell lysate. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Morphology of blends of linear and long-chain-branched polyethylenes in the solid state: A study by SANS, SAXS, and DSC

    International Nuclear Information System (INIS)

    Wignall, G.D.; Londono, J.D.; Lin, J.S.; Alamo, R.G.; Galante, M.J.; Mandelkern, L.

    1995-01-01

    Differential scanning calorimetry (DSC), small-angle neutron scattering (SANS), and X-ray scattering (SAXS) have been used to investigate the solid-state morphology of blends of linear (high density) and long-chain-branched (low-density) polyethylenes (HDPE/LDPE). The blends are homogeneous in the melt, as previously demonstrated by SANS using the contrast obtained by deuterating the linear polymer. However, due to the structural and melting point differences (∼ 20 C) between HDPE and LDPE, the components may phase segregate on slow cooling (0.75 C/min). For high concentrations (φ ≥ 0.5) of HDPE, relatively high rates of crystallization of the linear component lead to the formation of separate stacks of HDPE and LDPE lamellae, as indicated by two-peak SAXS curves. For predominantly branched blends, the difference in crystallization rate of the components becomes smaller and only one SAXS peak is observed, indicating that the two species are in the same lamellar stack. Moreover, the phases no longer consist of the pure component and the HDPE lamellae contain up to 15--20% LDPE (and vice versa). Rapid quenching into dry ice/2-propanol (-78 C) produces only one SAXS peak (and hence one lamellar stack) over the whole concentration range. The blends show extensive cocrystallization, along with a tendency for the branched material to be preferentially located in the amorphous interlamellar regions. For high concentrations (φ > 0.5) of HDPE-D, the overall scattering length density (SLD) is high and the excess concentration of LDPE between the lamellae enhances the SLD contrast between the crystalline and amorphous phases. Thus, the interlamellar spacing (long period) is clearly visible in the SANS pattern. The blend morphology is a strong function of the quenching rate, and samples quenched less rapidly (e.g., into water at 23 C) are similar to slowly cooled blends

  7. Bacterial membrane activity of a-peptide/b-peptoid chimeras: Influence of amino acid composition and chain length on the activity against different bacterial strains

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line; Knapp, Kolja M; Franzyk, Henrik

    2011-01-01

    and subsequent killing is usually not tested. In this report, six α-peptide/β-peptoid chimeras were examined for the effect of amino acid/peptoid substitutions and chain length on the membrane perturbation and subsequent killing of food-borne and clinical bacterial isolates. RESULTS: All six AMP analogues...... acid only had a minor effect on MIC values, whereas chain length had a profound influence on activity. All chimeras were less active against Serratia marcescens (MICs above 46 μM). The chimeras were bactericidal and induced leakage of ATP from Staphylococcus aureus and S. marcescens with similar time...... of onset and reduction in the number of viable cells. EDTA pre-treatment of S. marcescens and E. coli followed by treatment with chimeras resulted in pronounced killing indicating that disintegration of the Gram-negative outer membrane eliminated innate differences in susceptibility. Chimera chain length...

  8. Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient

    DEFF Research Database (Denmark)

    Zhou, J; Hertz, Jens Michael; Leinonen, A

    1992-01-01

    We have generated and characterized cDNA clones providing the complete amino acid sequence of the human type IV collagen chain whose gene has been shown to be mutated in X chromosome-linked Alport syndrome. The entire translation product has 1,685 amino acid residues. There is a 26-residue signal...

  9. Comparison of the Photovoltaic Characteristics and Nanostructure of Fullerenes Blended with Conjugated Polymers with Siloxane-Terminated and Branched Aliphatic Side Chains

    KAUST Repository

    Kim, Do Hwan

    2013-02-12

    All-organic bulk heterojunction solar cells based on blends of conjugated polymers with fullerenes have recently surpassed the 8% efficiency mark and are well on their way to the industrially relevant ∼15% threshold. Using a low band-gap conjugated polymer, we have recently shown that polymer side chain engineering can lead to dramatic improvement in the in-plane charge carrier mobility. In this article, we investigate the effectiveness of siloxy side chain derivatization in controlling the photovoltaic performance of polymer:[6,6]-phenyl-C[71]-butyric acid methyl ester (PC71BM) blends and hence its influence on charge transport in the out-of-plane direction relevant for organic solar cells. We find that, in neat blends, the photocurrent of the polymer with siloxy side chains (PII2T-Si) is 4 times greater than that in blends using the polymer with branched aliphatic side chains (PII2T-ref). This difference is due to a larger out-of-plane hole mobility for PII2T-Si brought about by a largely face-on crystallite orientation as well as more optimal nanoscale polymer:PC71BM mixing. However, upon incorporating a common processing additive, 1,8-diiodooctane (DIO), into the spin-casting blend solution and following optimization, the PII2T-ref:PC71BM OPV device performance undergoes a large improvement and becomes the better-performing device, almost independent of DIO concentration (>1%). We find that the precise amount of DIO plays a larger role in determining the efficiency of PII2T-Si:PC71BM, and even at its maximum, the device performance lags behind optimized PII2T-ref:PC71BM blends. Using a combination of atomic force microscopy and small- and wide-angle X-ray scattering, we are able to elucidate the morphological modifications associated with the DIO-induced changes in both the nanoscale morphology and the molecular packing in blend films. © 2012 American Chemical Society.

  10. Branched-chain alpha-keto acid catabolism via the gene products of the bkd operon in Enterococcus faecalis: a ne, secreted metabolite serving as a temporary redox sink.

    NARCIS (Netherlands)

    Ward, D.E.; van der Weijden, C.C.; van der Merwe, M.J.; Westerhoff, H.V.; Claiborne, A.; Snoep, J.L.

    2000-01-01

    Recently the bkd gene cluster from Enterococcus faecalis was sequenced, and it was shown that the gene products constitute a pathway for the catabolism of branched-chain α-keto acids. We have now investigated the regulation and physiological role of this pathway. Primer extension analysis identified

  11. Ethylmalonic aciduria is associated with an amino acid variant of short chain acyl-coenzyme A dehydrogenase

    DEFF Research Database (Denmark)

    Corydon, M J; Gregersen, N; Lehnert, W

    1996-01-01

    Ethylmalonic aciduria is a common biochemical finding in patients with inborn errors of short chain fatty acid beta-oxidation. The urinary excretion of ethylmalonic acid (EMA) may stem from decreased oxidation by short chain acyl-CoA dehydrogenase (SCAD) of butyryl-CoA, which is alternatively...

  12. Structural and Thermodynamic Basis for Weak Interactions between Dihydrolipoamide Dehydrogenase and Subunit-binding Domain of the Branched-chain [alpha]-Ketoacid Dehydrogenase Complex

    Energy Technology Data Exchange (ETDEWEB)

    Brautigam, Chad A.; Wynn, R. Max; Chuang, Jacinta L.; Naik, Mandar T.; Young, Brittany B.; Huang, Tai-huang; Chuang, David T. (AS); (UTSMC)

    2012-02-27

    The purified mammalian branched-chain {alpha}-ketoacid dehydrogenase complex (BCKDC), which catalyzes the oxidative decarboxylation of branched-chain {alpha}-keto acids, is essentially devoid of the constituent dihydrolipoamide dehydrogenase component (E3). The absence of E3 is associated with the low affinity of the subunit-binding domain of human BCKDC (hSBDb) for hE3. In this work, sequence alignments of hSBDb with the E3-binding domain (E3BD) of the mammalian pyruvate dehydrogenase complex show that hSBDb has an arginine at position 118, where E3BD features an asparagine. Substitution of Arg-118 with an asparagine increases the binding affinity of the R118N hSBDb variant (designated hSBDb*) for hE3 by nearly 2 orders of magnitude. The enthalpy of the binding reaction changes from endothermic with the wild-type hSBDb to exothermic with the hSBDb* variant. This higher affinity interaction allowed the determination of the crystal structure of the hE3/hSBDb* complex to 2.4-{angstrom} resolution. The structure showed that the presence of Arg-118 poses a unique, possibly steric and/or electrostatic incompatibility that could impede E3 interactions with the wild-type hSBDb. Compared with the E3/E3BD structure, the hE3/hSBDb* structure has a smaller interfacial area. Solution NMR data corroborated the interactions of hE3 with Arg-118 and Asn-118 in wild-type hSBDb and mutant hSBDb*, respectively. The NMR results also showed that the interface between hSBDb and hE3 does not change significantly from hSBDb to hSBDb*. Taken together, our results represent a starting point for explaining the long standing enigma that the E2b core of the BCKDC binds E3 far more weakly relative to other {alpha}-ketoacid dehydrogenase complexes.

  13. Saturated Branched Chain, Normal Odd-Carbon-Numbered, and n-3 (Omega-3) Polyunsaturated Fatty Acids in Freshwater Fish in the Northeastern United States.

    Science.gov (United States)

    Wang, Dong Hao; Jackson, James R; Twining, Cornelia; Rudstam, Lars G; Zollweg-Horan, Emily; Kraft, Clifford; Lawrence, Peter; Kothapalli, Kumar; Wang, Zhen; Brenna, J Thomas

    2016-10-04

    The fatty acid profiles of wild freshwater fish are poorly characterized as a human food source for several classes of fatty acids, particularly for branched chain fatty acids (BCFA), a major bioactive dietary component known to enter the US food supply primarily via dairy and beef fat. We evaluated the fatty acid content of 27 freshwater fish species captured in the northeastern US with emphasis on the BCFA and bioactive polyunsaturated fatty acids (PUFA) most associated with fish, specifically n-3 (omega-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Mean BCFA content across all species was 1.0 ± 0.5% (mean ± SD) of total fatty acids in edible muscle, with rainbow smelt (Osmerus mordax) and pumpkinseed (Lepomis gibbosus) the highest at >2% BCFA. In comparison, EPA + DHA constituted 28% ± 7% of total fatty acids. Across all fish species, the major BCFA were iso-15:0, anteiso-15:0, iso-16:0, iso-17:0 and anteiso-17:0. Fish skin had significantly higher BCFA content than muscle tissues, at 1.8% ± 0.7%, but lower EPA and DHA. Total BCFA in fish skins was positively related with that in muscle (r 2 = 0.6). The straight chain saturates n-15:0 and n-17:0 which have been identified previously as markers for dairy consumption were relatively high with means of 0.4% and 0.6%, respectively, and may be an underappreciated marker for seafood intake. Consuming a standardized portion, 70 g (2.5 oz), of wild freshwater fish contributes only small amounts of BCFA, 2.5-24.2 mg, to the American diet, while it adds surprisingly high amounts of EPA + DHA (107 mg to 558 mg).

  14. Changes in rocket salad phytochemicals within the commercial supply chain: Glucosinolates, isothiocyanates, amino acids and bacterial load increase significantly after processing.

    Science.gov (United States)

    Bell, Luke; Yahya, Hanis Nadia; Oloyede, Omobolanle Oluwadamilola; Methven, Lisa; Wagstaff, Carol

    2017-04-15

    Five cultivars of Eruca sativa and a commercial variety of Diplotaxis tenuifolia were grown in the UK (summer) and subjected to commercial growth, harvesting and processing, with subsequent shelf life storage. Glucosinolates (GSL), isothiocyanates (ITC), amino acids (AA), free sugars, and bacterial loads were analysed throughout the supply chain to determine the effects on phytochemical compositions. Bacterial load of leaves increased significantly over time and peaked during shelf life storage. Significant correlations were observed with GSL and AA concentrations, suggesting a previously unknown relationship between plants and endemic leaf bacteria. GSLs, ITCs and AAs increased significantly after processing and during shelf life. The supply chain did not significantly affect glucoraphanin concentrations, and its ITC sulforaphane significantly increased during shelf life in E. sativa cultivars. We hypothesise that commercial processing may increase the nutritional value of the crop, and have added health benefits for the consumer. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Critical role of alkyl chain branching of organic semiconductors in enabling solution-processed N-channel organic thin-film transistors with mobility of up to 3.50 cm² V(-1) s(-1).

    Science.gov (United States)

    Zhang, Fengjiao; Hu, Yunbin; Schuettfort, Torben; Di, Chong-an; Gao, Xike; McNeill, Christopher R; Thomsen, Lars; Mannsfeld, Stefan C B; Yuan, Wei; Sirringhaus, Henning; Zhu, Daoben

    2013-02-13

    Substituted side chains are fundamental units in solution processable organic semiconductors in order to achieve a balance of close intermolecular stacking, high crystallinity, and good compatibility with different wet techniques. Based on four air-stable solution-processed naphthalene diimides fused with 2-(1,3-dithiol-2-ylidene)malononitrile groups (NDI-DTYM2) that bear branched alkyl chains with varied side-chain length and different branching position, we have carried out systematic studies on the relationship between film microstructure and charge transport in their organic thin-film transistors (OTFTs). In particular synchrotron measurements (grazing incidence X-ray diffraction and near-edge X-ray absorption fine structure) are combined with device optimization studies to probe the interplay between molecular structure, molecular packing, and OTFT mobility. It is found that the side-chain length has a moderate influence on thin-film microstructure but leads to only limited changes in OTFT performance. In contrast, the position of branching point results in subtle, yet critical changes in molecular packing and leads to dramatic differences in electron mobility ranging from ~0.001 to >3.0 cm(2) V(-1) s(-1). Incorporating a NDI-DTYM2 core with three-branched N-alkyl substituents of C(11,6) results in a dense in-plane molecular packing with an unit cell area of 127 Å(2), larger domain sizes of up to 1000 × 3000 nm(2), and an electron mobility of up to 3.50 cm(2) V(-1) s(-1), which is an unprecedented value for ambient stable n-channel solution-processed OTFTs reported to date. These results demonstrate that variation of the alkyl chain branching point is a powerful strategy for tuning of molecular packing to enable high charge transport mobilities.

  16. The relationships between odd- and branched-chain fatty acids to ruminal fermentation parameters and bacterial populations with different dietary ratios of forage and concentrate.

    Science.gov (United States)

    Zhang, Y; Liu, K; Hao, X; Xin, H

    2017-12-01

    The objectives of this study were to investigate the effect of different dietary ratios of forage and concentrate (F:C) on ruminal odd- and branched-chain fatty acids (OBCFAs) contents and to evaluate the relationships between OBCFA and ruminal fermentation parameters as well as bacterial populations tested by real-time PCR technique. The experimental design was a 3 × 3 Latin square. Three rumen-fistulated dry Holstein cows were fed three rations with different dietary F:C ratios (F:C; 30:70, 50:50 and 70:30). The rumen samples were collected every two hours (0600, 0800, 1000, 1200, 1400, 1600, 1800, 2000, 2200, 2400, 0200 and 0400 h) over three consecutive days in each sampling period. The results showed that rumen OBCFA profiles are significantly (p ruminal OBCFAs had strong relationships with ruminal fermentation parameters and bacterial populations. In particular, the iso-fatty acids had potential power to predict butyrate and isoacids metabolized in the rumen, whereas the fatty acids with 17 carbon atoms correlated with ruminal NH 3 -N content. The OBCFA contents have different relationships with fibrolytic and starch bacteria in the rumen. C17:0 and its isomers might be used to predict populations of fibrolytic bacteria. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  17. Effects of kinase inhibitors and potassium phosphate (KPi) on site-specific phosphorylation of branched chain α-ketoacid dehydrogenase (BCKDH)

    International Nuclear Information System (INIS)

    Kuntz, M.J.; Shimomura, Y.; Ozawa, T.; Harris, R.A.

    1987-01-01

    BCKDH is phosphorylated by a copurifying kinase at two serine residues on the Elα subunit. Phosphorylation of both sites occurs at about the same rate initially, but inactivation is believed associated only with site 1 phosphorylation. The effects of KPi and known inhibitors of BCKDH kinase, α-chloroisocaproate (CIC) and branched chain α-ketoacids (BCKA), on the phosphorylation of purified rat liver BCKDH were studied. Site-specific phosphorylation was quantitated by thin-layer electrophoresis of tryptic peptides followed by densitometric scanning of autoradiograms. Addition of 5 mM KPi was found necessary to stabilize the BCKDH activity at 37 0 C. Increasing the KPi to 50 mM dramatically increased the CIC and BCKA inhibition of site 1 and site 2 phosphorylation. The finding of enhanced sensitivity of inhibitors with 50 mM KPi may facilitate identification of physiologically important kinase effectors. Regardless of the KPi concentration, CIC and the BCKA showed much more effective inhibition of site 2 than site 1 phosphorylation. Although site 1 is the primary inactivating site, predominant inhibition of site 2 phosphorylation may provide a means of modulating kinase/phosphatase control of BCKDH activity under steady state conditions

  18. Microhydration effect on structural, energetic and light scattering properties of first branched interstellar molecule ( i-PrCN)

    OpenAIRE

    Chakraborty, Sumana; Routh, Swati; Krishnappa, Madhu

    2015-01-01

    In this work, we have focused on microsolvation of isopropyl cyanide (i-PrCN) as isopropyl cyanide has been recently detected in interstellar space and is of great importance from the astrochemical and bio-chemical point of view for its branching carbon chains. Such branches are needed for many molecules crucial to life, such as the amino acids that build proteins. The phenomenon of the formation of hydrogen bond affects structure, energetic and electric properties of microhydrated isopropyl ...

  19. Partial molar volumes of proteins: amino acid side-chain contributions derived from the partial molar volumes of some tripeptides over the temperature range 10-90 degrees C.

    Science.gov (United States)

    Häckel, M; Hinz, H J; Hedwig, G R

    1999-11-15

    The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine, histidine, cysteine, proline, glutamic acid, and arginine, have been determined in aqueous solution over the temperature range 10-90 degrees C using differential scanning densitometry . These data, together with those reported previously, have been used to derive the partial molar volumes of the side-chains of all 20 amino acids. The side-chain volumes are critically compared with literature values derived using partial molar volumes for alternative model compounds. The new amino acid side-chain volumes, along with that for the backbone glycyl group, were used to calculate the partial specific volumes of several proteins in aqueous solution. The results obtained are compared with those observed experimentally. The new side-chain volumes have also been used to re-determine residue volume changes upon protein folding.

  20. Photoinduced electron transfer involving eosin-tryptophan conjugates. Long-lived radical pair states for systems incorporating aromatic amino acid side chains

    Energy Technology Data Exchange (ETDEWEB)

    Jones, G. II; Farahat, C.W.; Oh, C. (Boston Univ., MA (United States))

    1994-07-14

    The electron-transfer photochemistry of the covalent derivatives of the dye eosin, in which the xanthene dye is covalently attached to the amino acid L-tryptophan via the thiohydantoin derivative, the tryptophan dipeptide, and an ethyl ester derivative, has been investigated. The singlet excited state of the dye is significantly quenched on attachment of the aromatic amino acid residue. Dye triplet states are also intercepted through intramolecular interaction of excited dye and amino acid pendants. Flash photolysis experiments verify that this interaction involves electron transfer from the indole side chains of tryptophan. Rate constants for electron transfer are discussed in terms of the distance relationships for the eosin chromophore and aromatic redox sites on peptide derivatives, the pathway for [sigma]-[pi] through-bond interaction between redox sites, and the multiplicity and state of protonation for electron-transfer intermediates. Selected electron-transfer photoreactions were studied under conditions of binding of the peptide derivatives in a high molecular weight, water-soluble, globular polymer, poly(vinyl-2-pyrrolidinone). 28 refs., 4 figs., 1 tab.

  1. Plasma Amino Acids vs Conventional Predictors of Insulin Resistance Measured by the Hyperinsulinemic Clamp

    OpenAIRE

    Labonte, Cherise C.; Farsijani, Samaneh; Marliss, Errol B.; Gougeon, Réjeanne; Morais, José A.; Pereira, Sandra; Bassil, Maya; Winter, Aaron; Murphy, Jessica; Combs, Terry P.; Chevalier, Stéphanie

    2017-01-01

    Context: Specific plasma amino acid (AA) profiles including elevated postabsorptive branched-chain amino acids (BCAAs) have been associated with insulin resistance (IR), mostly estimated by homeostatic model assessment. This study assessed the associations of postabsorptive AAs with IR directly measured by insulin-mediated glucose disposal and determined the quantitative value of AAs and conventional IR predictors. Design: Fifty-one healthy, 31 overweight or obese (Ow/Ob), and 52 men and wome...

  2. Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects

    OpenAIRE

    Yamada, Chizumi; Kondo, Masumi; Kishimoto, Noriaki; Shibata, Takeo; Nagai, Yoko; Imanishi, Tadashi; Oroguchi, Takashige; Ishii, Naoaki; Nishizaki, Yasuhiro

    2015-01-01

    Aims/Introduction Elevation of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine, has been observed in obesity-related insulin resistance. However, there have been few studies on Asians, who are generally less obese and less insulin-resistant than Caucasian or African-Americans. In the present study, we investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) and plasma ami...

  3. Novel Countercation in MMX-Type Mixed-Valence Chain Compound: Coexistence of Neutral and Protonated Amino Substituents

    Directory of Open Access Journals (Sweden)

    Hiroaki Iguchi

    2011-10-01

    Full Text Available The first MMX-type quasi-one-dimensional (Q1D Pt chain complex (MMX chain that contains a mono-protonated diamine as countercation, {o-(H3NC6H4NH2}4[Pt2(pop4I]·H2O (pop = P2H2O52–, was synthesized. According to the crystal structural analysis, –NH2 group was hydrogen-bonded to either lattice H2O molecule or –NH3+ group in addition to typical hydrogen bond between –NH3+ group and pop ligand. To control the partial deprotonation of the countercation will be an important method for achieving the high-conductive MMX-chain polymer by the hole doping.

  4. Content and Composition of Branched-Chain Fatty Acids in Bovine Milk Are Affected by Lactation Stage and Breed of Dairy Cow.

    Science.gov (United States)

    Bainbridge, Melissa L; Cersosimo, Laura M; Wright, André-Denis G; Kraft, Jana

    2016-01-01

    Dairy products contain bioactive fatty acids (FA) and are a unique dietary source of an emerging class of bioactive FA, branched-chain fatty acids (BCFA). The objective of this study was to compare the content and profile of bioactive FA in milk, with emphasis on BCFA, among Holstein (HO), Jersey (JE), and first generation HO x JE crossbreeds (CB) across a lactation to better understand the impact of these factors on FA of interest to human health. Twenty-two primiparous cows (n = 7 HO, n = 7 CB, n = 8 JE) were followed across a lactation. All cows were fed a consistent total mixed ration (TMR) at a 70:30 forage to concentrate ratio. Time points were defined as 5 days in milk (DIM), 95 DIM, 185 DIM, and 275 DIM. HO and CB had a higher content of n-3 FA at 5 DIM than JE and a lower n-6:n-3 ratio. Time point had an effect on the n-6:n-3 ratio, with the lowest value observed at 5 DIM and the highest at 185 DIM. The content of vaccenic acid was highest at 5 DIM, yet rumenic acid was unaffected by time point or breed. Total odd and BCFA (OBCFA) were higher in JE than HO and CB at 185 and 275 DIM. Breed affected the content of individual BCFA. The content of iso-14:0 and iso-16:0 in milk was higher in JE than HO and CB from 95 to 275 DIM. Total OBCFA were affected by time point, with the highest content in milk at 275 DIM. In conclusion, HO and CB exhibited a higher content of several bioactive FA in milk than JE. Across a lactation the greatest content of bioactive FA in milk occurred at 5 DIM and OBCFA were highest at 275 DIM.

  5. Identification of a Key Gene Involved in Branched-Chain Short Fatty Acids Formation in Natto by Transcriptional Analysis and Enzymatic Characterization in Bacillus subtilis.

    Science.gov (United States)

    Hong, Chenlu; Chen, Yangyang; Li, Lu; Chen, Shouwen; Wei, Xuetuan

    2017-03-01

    Natto as a fermented soybean product has many health benefits for human due to its rich nutritional and functional components. However, the unpleasant odor of natto, caused by the formation of branched-chain short fatty acids (BCFAs), prohibits the wide acceptance of natto products. This work is to identify the key gene of BCFAs formation and develop the guidance to reduce natto odor. Transcriptional analysis of BCFAs synthesis pathway genes was conducted in two Bacillus subtilis strains with obvious different BCFAs synthesis abilities. The transcriptional levels of bcd, bkdAA, and ptb in B. subtilis H-9 were 2.7-fold, 0.7-fold, and 8.9-fold higher than that of B. subtilis H-4, respectively. Therefore, the ptb gene with the highest transcriptional change was considered as the key gene in BCFAs synthesis. The ptb encoded enzyme Ptb was further characterized by inducible expression in Escherichia coli. The recombinant Ptb protein (about 32 kDa) was verified by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis analysis. The catalysis functions of Ptb were confirmed on substrates of isovaleryl-CoA and isobutyryl-CoA, and the higher catalysis efficiency of Ptb on isovaleryl-CoA explained the higher level of isovaleric acid in natto. The optimal activities of Ptb were observed at 50 °C and pH 8.0, and the enzymatic activity was inhibited by Ca 2+ , Zn 2+ , Ba 2+ , Mn 2+ , Cu 2+ , SDS, and EDTA. Collectively, this study reports a key gene responsible for BCFAs formation in natto fermentation and provides potential strategies to solve the odor problem.

  6. New Mononuclear Cu(II Complexes and 1D Chains with 4-Amino-4H-1,2,4-triazole

    Directory of Open Access Journals (Sweden)

    Marinela M. Dîrtu

    2013-12-01

    Full Text Available The crystal structures of two mononuclear Cu(II NH2trz complexes [Cu(NH2trz4(H2O](AsF62 (I and [Cu(NH2trz4(H2O](PF62 (II as well as two coordination polymers [Cu(μ2-NH2trz2Cl]Cl∙H2O (III and [Cu(μ2-NH2trz2Cl] (SiF60.5∙1.5H2O (IV are presented. Cationic 1D chains with bridging bis-monodentate μ2-coordinated NH2trz and bridging μ2-coordinated chloride ligands are present in III and IV. In these coordination polymers, the Cu(II ions are strongly antiferromagnetically coupled with J = −128.4 cm−1 for III and J = −143 cm−1 for IV (H = −JΣSiSi+1, due to the nature of the bridges between spin centers. Inter-chain interactions present in the crystal structures were taken into consideration, as well as g factors, which were determined experimentally, for the quantitative modeling of their magnetic properties.

  7. Amino acid 489 is encoded by a mutational "hot spot" on the beta 3 integrin chain: the CA/TU human platelet alloantigen system.

    Science.gov (United States)

    Wang, R; McFarland, J G; Kekomaki, R; Newman, P J

    1993-12-01

    A new platelet alloantigen, termed CA, has recently been implicated in a case of neonatal alloimmune thrombocytopenia (NATP) in a Filipino family in Canada. Maternal anti-CA serum reacted with glycoprotein (GP) IIIa and maintained its reactivity after removal of high mannose carbohydrate residues from GPIIIa. The monoclonal antibody (MoAb) AP3 partially blocked binding of anti-CA to GPIIIa, suggesting that the CA polymorphism is proximal to the AP3 epitope. Platelet RNA polymerase chain reaction (PCR) was used to amplify the region of GPIIIa cDNA that encodes this region of the protein. DNA sequence analysis showed a GA nucleotide substitution at base 1564 that results in an arginine (Arg) (CGG)glutamine (Gln) (CAG) polymorphism in amino acid (AA) 489. Further analysis of PCR-amplified genomic DNA from 27 normal individuals showed that AA 489 is encoded by a mutational "hot spot" of the GPIIIa gene, as three different codons for the wild-type Arg489 of GPIIIa were also found. The codon usage for Arg489 was found to be: CGG (63%), CGA (37%), and CGC (Definition of these new molecular variants of the beta 3 integrin chain should prove valuable in the diagnosis of NATP in these two geographically disparate populations, and it may also provide useful genetic markers for examining other pathologic variations of the GPIIb-IIIa complex.

  8. Ecological genomics of Boechera stricta: Identification of a QTL controlling the allocation of methionine- vs branched-chain amino acid-derived glucosinolates and levels of insect herbivory

    NARCIS (Netherlands)

    Schranz, M.E.; Manzaneda, A.J.; Windsor, A.J.; Clauss, M.; Mitchell-Olds, T.

    2009-01-01

    In the Brassicaceae, glucosinolates influence the feeding, reproduction and development of many insect herbivores. Glucosinolate production and effects on herbivore feeding have been extensively studied in the model species, Arabidopsis thaliana and Brassica crops, both of which constitutively

  9. Modulation of fatty acid composition and growth in Sporosarcina species in response to temperatures and exogenous branched-chain amino acids.

    Science.gov (United States)

    Tsuda, Kentaro; Nagano, Hideaki; Ando, Akinori; Shima, Jun; Ogawa, Jun

    2017-06-01

    Psychrotolerant endospore-forming Sporosarcina species have been predominantly isolated from minced fish meat (surimi), which is stored under refrigeration after heat treatment. To develop a better method for preserving surimi-based food products, we studied the growth and fatty acid compositions of the isolated strain S92h as well as Sporosarcina koreensis and Sporosarcina aquimarina at cold and moderate temperatures. The growth rates of strain S92h and S. koreensis were the fastest and slowest at cold temperatures, respectively, although these strains grew at a similar rate at moderate temperatures. In all three strains, the proportions of anteiso-C 15:0 and unsaturated fatty acids (UFAs) were significantly higher at cold temperatures than at moderate temperatures. Furthermore, supplementation with valine, leucine, and isoleucine resulted in proportional increases in iso-C 16:0 , iso-C 15:0 , and anteiso-C 15:0 , respectively, among the fatty acid compositions of these strains. The proportions of the UFAs were also altered by the supplementation. At cold temperatures, the growth rates of strain S92h and S. koreensis, but not of S. aquimarina, were affected by supplementation with leucine. Supplementation with isoleucine enhanced the growth of S. koreensis at cold temperatures but not that of the other strains. Valine did not affect the growth of any strain. These results indicate that anteiso-C 15:0 and UFAs both play important roles in the cold tolerance of the genus Sporosarcina and that these bacteria modulate their fatty acid compositions in response to the growth environment.

  10. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

    DEFF Research Database (Denmark)

    Hernández-Alvarez, María Isabel; Díaz-Ramos, Angels; Berdasco, María

    2017-01-01

    The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused...... of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes....

  11. Higher Branched-Chain Amino Acid Intake Is Associated with a Lower Prevalence of Being Overweight or Obese in Middle-Aged East Asian and Western Adults12

    OpenAIRE

    Qin, Li‐Qiang; Xun, Pengcheng; Bujnowski, Deborah; Daviglus, Martha L.; Van Horn, Linda; Stamler, Jeremiah; He, Ka

    2010-01-01

    Beneficial effects on body weight of supplementation with BCAA, including leucine, isoleucine, and valine, have been observed in animal and human studies. However, population-based studies on dietary BCAA intake and body weight are lacking. The objective of this study was to examine the association between dietary BCAA intake and risk of overweight status/obesity among multi-ethnic populations. The International Study of Macro-/Micronutrients and Blood Pressure is a cross-sectional epidemiolo...

  12. Regional amino acid transport into brain during diabetes: Effect of plasma amino acids

    International Nuclear Information System (INIS)

    Mans, A.M.; DeJoseph, M.R.; Davis, D.W.; Hawkins, R.A.

    1987-01-01

    Transport of phenylalanine and lysine into the brain was measured in 4-wk streptozotocin-diabetic rats to assess the effect on the neutral and basic amino acid transport systems at the blood-brain barrier. Amino acid concentrations in plasma and brain were also measured. Regional permeability-times-surface area (PS) products and influx were determined using a continuous infusion method and quantitative autoradiography. The PS of phenylalanine was decreased by an average of 40% throughout the entire brain. Influx was depressed by 35%. The PS of lysine was increased by an average of 44%, but the influx was decreased by 27%. Several plasma neutral amino acids (branched chain) were increased, whereas all basic amino acids were decreased. Brain tryptophan, phenylalanine, tyrosine, methionine, and lysine contents were markedly decreased. The transport changes were almost entirely accounted for by the alterations in the concentrations of the plasma amino acids that compete for the neutral and basic amino acid carriers. The reduced influx could be responsible for the low brain content of some essential amino acids, with possibly deleterious consequences for brain functions

  13. Influence of specific amino acid side-chains on the antimicrobial activity and structure of bovine lactoferrampin.

    Science.gov (United States)

    Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J

    2012-06-01

    Lactoferrin is an 80 kDa iron binding protein found in the secretory fluids of mammals and it plays a major role in host defence. An antimicrobial peptide, lactoferrampin, was identified through sequence analysis of bovine lactoferrin and its antimicrobial activity against a wide range of bacteria and yeast species is well documented. In the present work, the contribution of specific amino acid residues of lactoferrampin was examined to evaluate the role that they play in membrane binding and bilayer disruption. The structures of all the bovine lactoferrampin derivatives were examined with circular dichroism and nuclear magnetic resonance spectroscopy, and their interactions with phospholipids were evaluated with differential scanning calorimetry and isothermal titration calorimetry techniques. From our results it is apparent that the amphipathic N-terminal helix anchors the peptide to membranes with Trp 268 and Phe 278 playing important roles in determining the strength of the interaction and for inducing peptide folding. In addition, the N-terminal helix capping residues (DLI) increase the affinity for negatively charged vesicles and they mediate the depth of membrane insertion. Finally, the unique flexibility in the cationic C-terminal region of bovine lactoferrampin does not appear to be essential for the antimicrobial activity of the peptide.

  14. Amino acid composition in parenteral nutrition: what is the evidence?

    Science.gov (United States)

    Yarandi, Shadi S.; Zhao, Vivian M.; Hebbar, Gautam; Ziegler, Thomas R.

    2011-01-01

    Purpose of review Complete parenteral nutrition solutions contain mixed amino acid products providing all nine essential amino acids and a varying composition of nonessential amino acids. Relatively little rigorous comparative efficacy research on altered parenteral nutrition amino acid composition has been published in recent years. Recent findings Limited data from randomized, double-blind, adequately powered clinical trials to define optimal doses of total or individual amino acids in parenteral nutrition are available. An exception is the growing number of studies on the efficacy of glutamine supplementation of parenteral nutrition or given as a single parenteral agent. Parenteral glutamine appears to confer benefit in selected patients; however, additional data to define optimal glutamine dosing and the patient subgroups who may most benefit from this amino acid are needed. Although some promising studies have been published, little data are available in the current era of nutrition support on the clinical efficacy of altered doses of arginine, branched chain amino acids, cysteine, or taurine supplementation of parenteral nutrition. Summary Despite routine use of parenteral nutrition, surprisingly little clinical efficacy data are available to guide total or specific amino acid dosing in adult and pediatric patients requiring this therapy. This warrants increased attention by the research community and funding agencies to better define optimal amino acid administration strategies in patient subgroups requiring parenteral nutrition. PMID:21076291

  15. Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

    Science.gov (United States)

    Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

  16. Poisson branching point processes

    International Nuclear Information System (INIS)

    Matsuo, K.; Teich, M.C.; Saleh, B.E.A.

    1984-01-01

    We investigate the statistical properties of a special branching point process. The initial process is assumed to be a homogeneous Poisson point process (HPP). The initiating events at each branching stage are carried forward to the following stage. In addition, each initiating event independently contributes a nonstationary Poisson point process (whose rate is a specified function) located at that point. The additional contributions from all points of a given stage constitute a doubly stochastic Poisson point process (DSPP) whose rate is a filtered version of the initiating point process at that stage. The process studied is a generalization of a Poisson branching process in which random time delays are permitted in the generation of events. Particular attention is given to the limit in which the number of branching stages is infinite while the average number of added events per event of the previous stage is infinitesimal. In the special case when the branching is instantaneous this limit of continuous branching corresponds to the well-known Yule--Furry process with an initial Poisson population. The Poisson branching point process provides a useful description for many problems in various scientific disciplines, such as the behavior of electron multipliers, neutron chain reactions, and cosmic ray showers

  17. Long branch-chains of amylopectin with B-type crystallinity in rice seed with inhibition of starch branching enzyme I and IIb resist in situ degradation and inhibit plant growth during seedling development : Degradation of rice starch with inhibition of SBEI/IIb during seedling development.

    Science.gov (United States)

    Pan, Ting; Lin, Lingshang; Wang, Juan; Liu, Qiaoquan; Wei, Cunxu

    2018-01-08

    Endosperm starch provides prime energy for cereal seedling growth. Cereal endosperm with repression of starch branching enzyme (SBE) has been widely studied for its high resistant starch content and health benefit. However, in barley and maize, the repression of SBE changes starch component and amylopectin structure which affects grain germination and seedling establishment. A high resistant starch rice line (TRS) has been developed through inhibiting SBEI/IIb, and its starch has very high resistance to in vitro hydrolysis and digestion. However, it is unclear whether the starch resists in situ degradation in seed and influences seedling growth after grain germination. In this study, TRS and its wild-type rice cultivar Te-qing (TQ) were used to investigate the seedling growth, starch property changes, and in situ starch degradation during seedling growth. The slow degradation of starch in TRS seed restrained the seedling growth. The starch components including amylose and amylopectin were simultaneously degraded in TQ seeds during seedling growth, but in TRS seeds, the amylose was degraded faster than amylopectin and the amylopectin long branch-chains with B-type crystallinity had high resistance to in situ degradation. TQ starch was gradually degraded from the proximal to distal region of embryo and from the outer to inner in endosperm. However, TRS endosperm contained polygonal, aggregate, elongated and hollow starch from inner to outer. The polygonal starch similar to TQ starch was completely degraded, and the other starches with long branch-chains of amylopectin and B-type crystallinity were degraded faster at the early stage of seedling growth but had high resistance to in situ degradation during TRS seedling growth. The B-type crystallinity and long branch-chains of amylopectin in TRS seed had high resistance to in situ degradation, which inhibited TRS seedling growth.

  18. Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission Tomography Imaging of Tumors

    Science.gov (United States)

    Sun, Aixia; Liu, Xiang; Tang, Ganghua

    2017-12-01

    Tumor cells have an increased nutritional demand for amino acids(AAs) to satisfy their rapid proliferation. Positron-emitting nuclide labeled AAs are interesting probes and are of great importance for imaging tumors using positron emission tomography (PET). Carbon-11 and fluorine-18 labeled AAs include the [1-11C] amino acids, labeling alpha-C- amino acids, the branched-chain of amino acids and N-substituted carbon-11 labeled amino acids. These tracers target protein synthesis or amino acid(AA) transport, and their uptake mechanism mainly involves AA transport. AA PET tracers have been widely used in clinical settings to image brain tumors, neuroendocrine tumors, prostate cancer, breast cancer, non–small cell lung cancer (NSCLC) and hepatocellular carcinoma. This review focuses on the fundamental concepts and the uptake mechanism of AAs, AA PET tracers and their clinical applications.

  19. alpha-Ketoglutarate application in hemodialysis patients improves amino acid metabolism.

    Science.gov (United States)

    Riedel, E; Nündel, M; Hampl, H

    1996-01-01

    In hemodialysis patients, free amino acids and alpha-ketoacids in plasma were determined by fluorescence HPLC to assess the effect of alpha-ketoglutarate administration in combination with the phosphate binder calcium carbonate on the amino acid metabolism. During 1 year of therapy in parallel to inorganic phosphate, urea in plasma decreased significantly, histidine, arginine and proline as well as branched chain alpha-ketoacids, in particular alpha-ketoisocaproate, a regulator of protein metabolism, increased. Thus, administration of alpha-ketoglutarate with calcium carbonate effectively improves amino acid metabolism in hemodialysis patients as it decreases hyperphosphatemia.

  20. Amino acid metabolic signaling influences Aedes aegypti midgut microbiome variability.

    Directory of Open Access Journals (Sweden)

    Sarah M Short

    2017-07-01

    Full Text Available The mosquito midgut microbiota has been shown to influence vector competence for multiple human pathogens. The microbiota is highly variable in the field, and the sources of this variability are not well understood, which limits our ability to understand or predict its effects on pathogen transmission. In this work, we report significant variation in female adult midgut bacterial load between strains of A. aegypti which vary in their susceptibility to dengue virus. Composition of the midgut microbiome was similar overall between the strains, with 81-92% of reads coming from the same five bacterial families, though we did detect differences in the presence of some bacterial families including Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on the two mosquito strains that showed the greatest difference in bacterial load, and found that they differ in transcript abundance of many genes implicated in amino acid metabolism, in particular the branched chain amino acid degradation pathway. We then silenced this pathway by targeting multiple genes using RNA interference, which resulted in strain-specific bacterial proliferation, thereby eliminating the difference in midgut bacterial load between the strains. This suggests that the branched chain amino acid (BCAA degradation pathway controls midgut bacterial load, though the mechanism underlying this remains unclear. Overall, our results indicate that amino acid metabolism can act to influence the midgut microbiota. Moreover, they suggest that genetic or physiological variation in BCAA degradation pathway activity may in part explain midgut microbiota variation in the field.

  1. Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidine-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

    International Nuclear Information System (INIS)

    Rojas, Fernando A.; Kouznetsov, Vladimir V.

    2011-01-01

    In the present work, the syntheses of new 4-amino-7-chloroquinoline N-derivatives were performed by selective modification of the side chain amino group of N-(7-chloroquinoline-4-yl) alkyldiamines, basis framework of chloroquine (CQ) drug through the incorporation of heterocyclic 2-imino-thiazolidine-4-one and 1 H-pyrrol-2,5-dione systems. These potential activity modulators were selected thanks to their characteristic properties, and evaluated by virtual screening employing the OSIRIS and Molinspirations platforms. Designed and synthesized quinolinic derivatives could increase the antimalarial activity of CQ analogues without affecting the lipophilicity as described in literature, suggesting them as candidates for further biological assessments. (author)

  2. Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidine-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

    Energy Technology Data Exchange (ETDEWEB)

    Rojas, Fernando A; Kouznetsov, Vladimir V., E-mail: kouznet@uis.edu.co [Laboratorio de Quimica Organica y Biomolecular, Escuela de Quimica, Universidad Industrial de Santander, Bucaramanga (Colombia)

    2011-09-15

    In the present work, the syntheses of new 4-amino-7-chloroquinoline N-derivatives were performed by selective modification of the side chain amino group of N-(7-chloroquinoline-4-yl) alkyldiamines, basis framework of chloroquine (CQ) drug through the incorporation of heterocyclic 2-imino-thiazolidine-4-one and {sup 1}H-pyrrol-2,5-dione systems. These potential activity modulators were selected thanks to their characteristic properties, and evaluated by virtual screening employing the OSIRIS and Molinspirations platforms. Designed and synthesized quinolinic derivatives could increase the antimalarial activity of CQ analogues without affecting the lipophilicity as described in literature, suggesting them as candidates for further biological assessments. (author)

  3. Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats.

    Science.gov (United States)

    Yeh, S; Chao, C; Lin, M; Chen, W

    2000-04-01

    This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on

  4. Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain

    OpenAIRE

    Iwaniuk, Daniel P.; Whetmore, Eric D.; Rosa, Nicholas; Ekoue-Kovi, Kekeli; Alumasa, John; de Dios, Angel C.; Roepe, Paul D.; Wolf, Christian

    2009-01-01

    We report the synthesis and in vitro antimalarial activity of several new 4-amino-and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of P. falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11–15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain st...

  5. Radioinitiation of Chain Branched Reactions and its Sensitization; Amorcage sous rayonnement des reactions par ramification en chaine; sensibilisation du processus; Radiatsionnoe initsiirovanie tsennykh razvetvlennykh reaktsij i ego sensibilizatsiya; Radioiniciacion de reacciones en cadena ramificadas y medios para aumentar su sensibilidad

    Energy Technology Data Exchange (ETDEWEB)

    Barelko, E V; Kartashova, L I; Komarov, P N; Proskurnin, M A [Karpov Physico-Chemical Institute, Moscow, Union of Soviet Socialist Republics (Russian Federation)

    1960-07-15

    This paper describes the results of experiments by the writers with radioinitiation of chain branched reactions of the oxidation of organic compounds. The function of radiation as an initiating agent is described with reference to the oxidation of several unsaturated hydrocarbons and butanol. The reaction is self-accelerating and proceeds spontaneously after radiation has ceased. A detailed investigation was made of a process from oxidizing benzene, which has a high radiation resistance. The writers devised a method of sensitizing the radioinitiation of the oxidation of radiation-resistant substances by chemically inert but non-radiation-resistant substances. The main quantitative features of the process for the radiooxidation of benzene are stated to be the accumulation of various reaction products, and the effect of temperature, pressure, power and radiation dosage on the process of such accumulation. Information was obtained about the mechanism of the process. The design of circulating equipment is described. (author) [French] Dans ce memoire, les auteurs presentent les resultats d'une etude consacree a l'amorcage sous rayonnement de reactions, d'oxydation des composes organiques, par ramification en chaine. Ils montrent le role des rayonnements en tant qu'agents d'amorcage de la reaction, en citant comme exemples l'oxydation de certains hydrocarbures non satures et du butanol. La reaction possede un caractere d'auto-acceleration et continue spontanement lorsque l'action des rayonnements a cesse. La reaction d'oxydation du benzene a ete etudiee en detail; elle est caracterisee par la haute stabilite de la substance vis-a-vis de l'action des rayonnements. Les auteurs formulent les principes de la sensibilisation, par l'action de substances instables vis-a-vis des rayonnements de l'amorcage sous rayonnement de la reaction d'oxydation de substances stables vis-a-vis des rayonnements et chimiquement inertes. Le memoire fournit les caracteristiques quantitatives

  6. Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Directory of Open Access Journals (Sweden)

    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  7. A Canonical Biotin Synthesis Enzyme, 8-Amino-7-Oxononanoate Synthase (BioF), Utilizes Different Acyl Chain Donors in Bacillus subtilis and Escherichia coli.

    Science.gov (United States)

    Manandhar, Miglena; Cronan, John E

    2018-01-01

    BioF (8-amino-7-oxononanoate synthase) is a strictly conserved enzyme that catalyzes the first step in assembly of the fused heterocyclic rings of biotin. The BioF acyl chain donor has long been thought to be pimeloyl-CoA. Indeed, in vitro the Escherichia coli and Bacillus sphaericus enzymes have been shown to condense pimeloyl-CoA with l-alanine in a pyridoxal 5'-phosphate-dependent reaction with concomitant CoA release and decarboxylation of l-alanine. However, recent in vivo studies of E. coli and Bacillus subtilis suggested that the BioF proteins of the two bacteria could have different specificities for pimelate thioesters in that E. coli BioF may utilize either pimeloyl coenzyme A (CoA) or the pimelate thioester of the acyl carrier protein (ACP) of fatty acid synthesis. In contrast, B. subtilis BioF seemed likely to be specific for pimeloyl-CoA and unable to utilize pimeloyl-ACP. We now report genetic and in vitro data demonstrating that B. subtilis BioF specifically utilizes pimeloyl-CoA. IMPORTANCE Biotin is an essential vitamin required by mammals and birds because, unlike bacteria, plants, and some fungi, these organisms cannot make biotin. Currently, the biotin included in vitamin tablets and animal feeds is made by chemical synthesis. This is partly because the biosynthetic pathways in bacteria are incompletely understood. This paper defines an enzyme of the Bacillus subtilis pathway and shows that it differs from that of Escherichia coli in the ability to utilize specific precursors. These bacteria have been used in biotin production and these data may aid in making biotin produced by biotechnology commercially competitive with that produced by chemical synthesis. Copyright © 2017 American Society for Microbiology.

  8. Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes?

    Science.gov (United States)

    Rothman, Douglas L; De Feyter, Henk M; Maciejewski, Paul K; Behar, Kevin L

    2012-11-01

    The high in vivo flux of the glutamate/glutamine cycle puts a strong demand on the return of ammonia released by phosphate activated glutaminase from the neurons to the astrocytes in order to maintain nitrogen balance. In this paper we review several amino acid shuttles that have been proposed for balancing the nitrogen flows between neurons and astrocytes in the glutamate/glutamine cycle. All of these cycles depend on the directionality of glutamate dehydrogenase, catalyzing reductive glutamate synthesis (forward reaction) in the neuron in order to capture the ammonia released by phosphate activated glutaminase, while catalyzing oxidative deamination of glutamate (reverse reaction) in the astrocytes to release ammonia for glutamine synthesis. Reanalysis of results from in vivo experiments using (13)N and (15)N labeled ammonia and (15)N leucine in rats suggests that the maximum flux of the alanine/lactate or branched chain amino acid/branched chain amino acid transaminase shuttles between neurons and astrocytes are approximately 3-5 times lower than would be required to account for the ammonia transfer from neurons to astrocytes needed for glutamine synthesis (amide nitrogen) to sustain the glutamate/glutamine cycle. However, in the rat brain both the total ammonia fixation rate by glutamate dehydrogenase and the total branched chain amino acid transaminase activity are sufficient to support a branched chain amino acid/branched chain keto acid shuttle, as proposed by Hutson and coworkers, which would support the de novo synthesis of glutamine in the astrocyte to replace the ~20 % of neurotransmitter glutamate that is oxidized. A higher fraction of the nitrogen needs of total glutamate neurotransmitter cycling could be supported by hybrid cycles in which glutamate and tricarboxylic acid cycle intermediates act as a nitrogen shuttle. A limitation of all in vivo studies in animals conducted to date is that none have shown transfer of nitrogen for glutamine amide

  9. New Functions and Potential Applications of Amino Acids.

    Science.gov (United States)

    Uneyama, Hisayuki; Kobayashi, Hisamine; Tonouchi, Naoto

    Currently, several types of amino acids are being produced and used worldwide. Nevertheless, several new functions of amino acids have been recently discovered that could result in other applications. For example, oral stimulation by glutamate triggers the cephalic phase response to prepare for food digestion. Further, the stomach and intestines have specific glutamate-recognizing systems in their epithelial mucosa. Regarding clinical applications, addition of monosodium glutamate to the medicinal diet has been shown to markedly enhance gastric secretion in a vagus-dependent manner. Branched-chain amino acids (BCAAs) are the major components of muscles, and ingestion of BCAAs has been found to be effective for decreasing muscle pain. BCAAs are expected to be a solution for the serious issue of aging. Further, ingestion of specific amino acids could be beneficial. Glycine can be ingested for good night's sleep: glycine ingestion before bedtime significantly improved subjective sleep quality. Ingestion of alanine and glutamine effectively accelerates alcohol metabolism, and ingestion of cystine and theanine effectively prevents colds. Finally, amino acids could be used in a novel clinical diagnostic method: the balance of amino acids in the blood could be an indicator of the risk of diseases such as cancer. These newly discovered functions of amino acids are expected to contribute to the resolution of various issues.

  10. Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up

    OpenAIRE

    Mook-Kanamori, D. O.; Römisch-Margl, W.; Kastenmüller, G.; Prehn, C.; Petersen, A. K.; Illig, T.; Gieger, C.; Wang-Sattler, R.; Meisinger, C.; Peters, A.; Adamski, J.; Suhre, K.

    2014-01-01

    Background Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). Aim We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. Materials and methods We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia...

  11. Bayesian estimation for quantification by real-time polymerase chain reaction under a branching process model of the DNA molecules amplification process

    NARCIS (Netherlands)

    Lalam, N.; Jacob, C.

    2007-01-01

    The aim of Quantitative Polymerase Chain Reaction is to determine the initial amount X0 of specific nucleic acids from an observed trajectory of the amplification process, the amplification being achieved through successive replication cycles. This process depends on the efficiency fpngn of

  12. Utilization of alimentary protein and amino acids in satisfying the nitrogen requirements of monogastric mammals

    International Nuclear Information System (INIS)

    Pion, R.; Arnal, M.

    1976-01-01

    The nitrogenous matter in the food of monogastric animals consists mainly of proteins, which are rapidly hydrolized in the intestinal tract when they have left the gastric reservoir. The digestive tube has several roles: it provides for hydrolysis of the food proteins and for a supply of endogenous nitrogen; it enables a certain digestive function to be performed by the intestinal flora and permits the transport of amino acids into the blood, selecting those which are needed for protein synthesis. The digestion products appear mainly in the form of free amino acids in the portal blood. A large proportion of these amino acids is taken up by the liver, so that intense protein synthesis takes place in the latter, coupled with a decrease in catabolism leading to a rhythmic increase in the liver content of proteins and RNA. The labile proteins retained are mainly enzymes, which catabolize the amino acids, and the liver is the site of the catabolism of most of the excess amino acids except those with chain branching. Alimentary deficiencies do not markedly reduce protein synthesis in this organ, since the rate of re-utilization of the amino acids is increased and the liver thus plays a regulatory role. The utilization of amino acids in muscle also follows a certain rhythm, partly connected with feeding, and under hormonal control. The muscle is the seat of catabolism of a large part of the branched chain amino acids, and like the liver it contributes to the energy utilization of amino acids. The rate of utilization of certain essential amino acids can be measured by metabolic criteria, including determination of blood and muscle concentrations and excretion of 14 CO 2 labels in the exhaled air or of 35 S labels in urine. (author)

  13. Thermodynamic Modeling of Several Aqueous Alkanol Solutions Containing Amino Acids with the Perturbed-Chain Statistical Associated Fluid Theory Equation of State

    DEFF Research Database (Denmark)

    Ferreira, Luisa; Breil, Martin Peter; Pinho, S. P.

    2009-01-01

    parameters for the amino acids were fitted to the densities, activity and osmotic coefficients, vapor pressures, and water activity of their aqueous solutions. The solubilities of amino acids in pure and mixed solvent systems were calculated on the basis of the phase equilibrium conditions for a pure solid...... and a fluid phase. The hypothetical melting properties of each amino acid were fitted, to accurately correlate the solubilities in pure water. Only one temperature independent binary parameter is required for each amino acid/solvent pair. The model can accurately describe the solubility of the amino acids...... in water, but the correlation for the solubility in pure alcohols was not so satisfactory. The solubility in mixed solvents (ternary systems) was predicted on the basis of the modeling of the solubility in pure solvents, without any additional fitting of the parameters, and the results achieved were...

  14. Characterization of the B-chain of human plasma α2HS-glycoprotein. The complete amino acid sequence and primary structure of its heteroglycan

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Gejyo, F.; Chang, J.-L.; Bürgi, W.; Schmid, K.; Offner, G.D.; Troxler, R.F.; Halbeek, H. van

    1983-01-01

    α2HS-Glycoprotein, a normal human plasma protein, was recently shown to consist of two polypeptide chains. In the present study, we have separated these two chains from one another and have elucidated the complete primary structure of the B-chain. Employing automated Edman degradation, the

  15. Poly(ester amide)s based on (L)-lactic acid oligomers and α-amino acids: influence of the α-amino acid side chain in the poly(ester amide)s properties.

    Science.gov (United States)

    Fonseca, Ana C; Coelho, Jorge F J; Valente, Joana F A; Correia, Tiago R; Correia, Ilídio J; Gil, Maria H; Simões, Pedro N

    2013-01-01

    Novel biodegradable and low cytotoxic poly(ester amide)s (PEAs) based on α-amino acids and (L)-lactic acid (L-LA) oligomers were successfully synthesized by interfacial polymerization. The chemical structure of the new polymers was confirmed by spectroscopic analyses. Further characterization suggests that the α-amino acid plays a critical role on the final properties of the PEA. L-phenylalanine provides PEAs with higher glass transition temperature, whereas glycine enhances the crystallinity. The hydrolytic degradation in PBS (pH = 7.4) at 37 °C also depends on the α-amino acid, being faster for glycine-based PEAs. The cytotoxic profiles using fibroblast human cells indicate that the PEAs did not elicit an acute cytotoxic effect. The strategy presented in this work opens the possibility of synthesizing biodegradable PEAs with low citotoxicity by an easy and fast method. It is worth to mention also that the properties of these materials can be fine-tuned only by changing the α-amino acid.

  16. Amino Acid Composition of an Organic Brown Rice Protein Concentrate and Isolate Compared to Soy and Whey Concentrates and Isolates

    Directory of Open Access Journals (Sweden)

    Douglas S. Kalman

    2014-06-01

    Full Text Available A protein concentrate (Oryzatein-80™ and a protein isolate (Oryzatein-90™ from organic whole-grain brown rice were analyzed for their amino acid composition. Two samples from different batches of Oryzatein-90™ and one sample of Oryzatein-80™ were provided by Axiom Foods (Los Angeles, CA, USA. Preparation and analysis was carried out by Covance Laboratories (Madison, WI, USA. After hydrolysis in 6-N hydrochloric acid for 24 h at approximately 110 °C and further chemical stabilization, samples were analyzed by HPLC after pre-injection derivitization. Total amino acid content of both the isolate and the concentrate was approximately 78% by weight with 36% essential amino acids and 18% branched-chain amino acids. These results are similar to the profiles of raw and cooked brown rice except in the case of glutamic acid which was 3% lower in the isolate and concentrate. The amino acid content and profile of the Oryzatein-90™ isolate was similar to published values for soy protein isolate but the total, essential, and branched-chain amino acid content of whey protein isolate was 20%, 39% and 33% greater, respectively, than that of Oryzatein-90™. These results provide a valuable addition to the nutrient database of protein isolates and concentrates from cereal grains.

  17. Amino Acid Composition of an Organic Brown Rice Protein Concentrate and Isolate Compared to Soy and Whey Concentrates and Isolates.

    Science.gov (United States)

    Kalman, Douglas S

    2014-06-30

    A protein concentrate (Oryzatein-80™) and a protein isolate (Oryzatein-90™) from organic whole-grain brown rice were analyzed for their amino acid composition. Two samples from different batches of Oryzatein-90™ and one sample of Oryzatein-80™ were provided by Axiom Foods (Los Angeles, CA, USA). Preparation and analysis was carried out by Covance Laboratories (Madison, WI, USA). After hydrolysis in 6-N hydrochloric acid for 24 h at approximately 110 °C and further chemical stabilization, samples were analyzed by HPLC after pre-injection derivitization. Total amino acid content of both the isolate and the concentrate was approximately 78% by weight with 36% essential amino acids and 18% branched-chain amino acids. These results are similar to the profiles of raw and cooked brown rice except in the case of glutamic acid which was 3% lower in the isolate and concentrate. The amino acid content and profile of the Oryzatein-90™ isolate was similar to published values for soy protein isolate but the total, essential, and branched-chain amino acid content of whey protein isolate was 20%, 39% and 33% greater, respectively, than that of Oryzatein-90™. These results provide a valuable addition to the nutrient database of protein isolates and concentrates from cereal grains.

  18. Expression of an estrogen-regulated variant transcript of the peroxisomal branched chain fatty acid oxidase ACOX2 in breast carcinomas

    International Nuclear Information System (INIS)

    Bjørklund, Sunniva Stordal; Kristensen, Vessela N.; Seiler, Michael; Kumar, Surendra; Alnæs, Grethe I. Grenaker; Ming, Yao; Kerrigan, John; Naume, Bjørn; Sachidanandam, Ravi; Bhanot, Gyan; Børresen-Dale, Anne-Lise; Ganesan, Shridar

    2015-01-01

    Alternate transcripts from a single gene locus greatly enhance the combinatorial flexibility of the human transcriptome. Different patterns of exon usage have been observed when comparing normal tissue to cancers, suggesting that variant transcripts may play a role in the tumor phenotype. Ribonucleic acid-sequencing (RNA-seq) data from breast cancer samples was used to identify an intronic start variant transcript of Acyl-CoA oxidase 2, ACOX2 (ACOX2-i9). Difference in expression between Estrogen Receptor (ER) positive and ER negative patients was assessed by the Wilcoxon rank sum test, and the findings validated in The Cancer Genome Atlas (TCGA) breast cancer dataset (BRCA). ACOX2-i9 expression was also assessed in cell lines using both quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot analysis. Knock down by short hairpin RNA (shRNA) and colony formation assays were used to determine whether ACOX2-i9 expression would influence cellular fitness. The effect of ACOX2-i9 expression on patient survival was assessed by the Kaplan-Meier survival function, and association to clinical parameters was analyzed using a Fisher exact test. The expression and translation of ACOX2-i9 into a 25 kDa protein was demonstrated in HepG2 cells as well as in several breast cancer cell lines. shRNA knock down of the ACOX2-i9 variant resulted in decreased cell viability of T47D and MDA-MB 436 cells. Moreover, expression of ACOX2-i9 was shown to be estrogen regulated, being induced by propyl pyrazoletriol and inhibited by tamoxifen and fulvestrant in ER+ T47D and Mcf-7 cells, but not in the ER- MDA-MB 436 cell line. This variant transcript showed expression predominantly in ER-positive breast tumors as assessed in our initial set of 53 breast cancers and further validated in 87 tumor/normal pairs from the TCGA breast cancer dataset, and expression was associated with better outcome in ER positive patients. ACOX2-i9 is specifically enriched in ER+ breast

  19. Expression of an estrogen-regulated variant transcript of the peroxisomal branched chain fatty acid oxidase ACOX2 in breast carcinomas.

    Science.gov (United States)

    Bjørklund, Sunniva Stordal; Kristensen, Vessela N; Seiler, Michael; Kumar, Surendra; Alnæs, Grethe I Grenaker; Ming, Yao; Kerrigan, John; Naume, Bjørn; Sachidanandam, Ravi; Bhanot, Gyan; Børresen-Dale, Anne-Lise; Ganesan, Shridar

    2015-07-17

    Alternate transcripts from a single gene locus greatly enhance the combinatorial flexibility of the human transcriptome. Different patterns of exon usage have been observed when comparing normal tissue to cancers, suggesting that variant transcripts may play a role in the tumor phenotype. Ribonucleic acid-sequencing (RNA-seq) data from breast cancer samples was used to identify an intronic start variant transcript of Acyl-CoA oxidase 2, ACOX2 (ACOX2-i9). Difference in expression between Estrogen Receptor (ER) positive and ER negative patients was assessed by the Wilcoxon rank sum test, and the findings validated in The Cancer Genome Atlas (TCGA) breast cancer dataset (BRCA). ACOX2-i9 expression was also assessed in cell lines using both quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot analysis. Knock down by short hairpin RNA (shRNA) and colony formation assays were used to determine whether ACOX2-i9 expression would influence cellular fitness. The effect of ACOX2-i9 expression on patient survival was assessed by the Kaplan-Meier survival function, and association to clinical parameters was analyzed using a Fisher exact test. The expression and translation of ACOX2-i9 into a 25 kDa protein was demonstrated in HepG2 cells as well as in several breast cancer cell lines. shRNA knock down of the ACOX2-i9 variant resulted in decreased cell viability of T47D and MDA-MB 436 cells. Moreover, expression of ACOX2-i9 was shown to be estrogen regulated, being induced by propyl pyrazoletriol and inhibited by tamoxifen and fulvestrant in ER+ T47D and Mcf-7 cells, but not in the ER- MDA-MB 436 cell line. This variant transcript showed expression predominantly in ER-positive breast tumors as assessed in our initial set of 53 breast cancers and further validated in 87 tumor/normal pairs from the TCGA breast cancer dataset, and expression was associated with better outcome in ER positive patients. ACOX2-i9 is specifically enriched in ER+ breast

  20. Lipase-catalyzed kinetic resolution of branched chain fatty acids and their esters : a study towards the production of enantiopure 4-methyloctanoic acid = Lipase-gekatalyseerde kinetische resolutie van vertakte vetzuren en hun esters : een studie naar de productie van enantiomeer zuiver 4-methyloctaanzuur

    NARCIS (Netherlands)

    Heinsman, N.W.J.T.

    2000-01-01

    Flavors and fragrances make an important contribution to the taste and smell of all kinds of food products both as natural occurring components and as additional flavors or fragrances. One of these flavor components is 4-methyloctanoic acid (4-MOA). This branched chain fatty acid

  1. Amino acids

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  2. Improvement in the mechanical properties, proton conductivity, and methanol resistance of highly branched sulfonated poly(arylene ether)/graphene oxide grafted with flexible alkylsulfonated side chains nanocomposite membranes

    Science.gov (United States)

    Liu, Dong; Peng, Jinhua; Li, Zhuoyao; Liu, Bin; Wang, Lei

    2018-02-01

    Sulfonated polymer/graphene oxide (GO) nanocomposites exhibit excellent properties as proton exchange membranes. However, few investigations on highly branched sulfonated poly(arylene ether)s (HBSPE)/GO nanocomposites as proton exchange membranes are reported. In order to obtain HBSPE-based nanocomposite membranes with better dispersibility and properties, a novel GO containing flexible alkylsulfonated side chains (SGO) is designed and prepared for the first time in this work. The HBSPE/SGO nanocomposite membranes with excellent dispersibility are successfully prepared. The properties of these membranes, including the mechanical properties, ion-exchange capacity, water uptake, proton conductivity, and methanol resistance, are characterized. The nanocomposite membranes exhibit higher tensile strength (32.67 MPa), higher proton conductivity (0.39 S cm-1 at 80 °C) and lower methanol permeability (4.89 × 10-7 cm2 s-1) than the pristine membrane. The nanocomposite membranes also achieve a higher maximum power density (82.36 mW cm-2) than the pristine membrane (67.85 mW cm-2) in single-cell direct methanol fuel cell (DMFC) tests, demonstrating their considerable potential for applications in DMFCs.

  3. Density functional theory with van der waals corrections study of the adsorption of alkyl, alkylthiol, alkoxyl, and amino-alkyl chains on the H:Si(111) surface.

    Science.gov (United States)

    Arefi, Hadi H; Nolan, Michael; Fagas, Giorgos

    2014-11-11

    Surface modification of silicon with organic monolayers tethered to the surface by different linkers is an important process in realizing future miniaturized electronic and sensor devices. Understanding the roles played by the nature of the linking group and the chain length on the adsorption structures and stabilities of these assemblies is vital to advance this technology. This paper presents a density functional theory (DFT) study of the hydrogen passivated Si(111) surface modified with alkyl chains of the general formula H:Si-(CH2)n-CH2 and H:Si-X-(CH2)n-CH3, where X = NH, O, S and n = (0, 1, 3, 5, 7, 9, 11), at half coverage. For (X)-hexane and (X)-dodecane functionalization, we also examined various coverages up to full monolayer grafting in order to validate the result of half covered surface and the linker effect on the coverage. We find that it is necessary to take into account the van der Waals interaction between the alkyl chains. The strongest binding is for the oxygen linker, followed by S, N, and C, irrespective of chain length. The result revealed that the sequence of the stability is independent of coverage; however, linkers other than carbon can shift the optimum coverage considerably and allow further packing density. For all linkers apart from sulfur, structural properties, in particular, surface-linker-chain angles, saturate to a single value once n > 3. For sulfur, we identify three regimes, namely, n = 0-3, n = 5-7, and n = 9-11, each with its own characteristic adsorption structures. Where possible, our computational results are shown to be consistent with the available experimental data and show how the fundamental structural properties of modified Si surfaces can be controlled by the choice of linking group and chain length.

  4. Critical role in CXCR4 signaling and internalization of the polypeptide main chain in the amino terminus of SDF-1α probed by novel N-methylated synthetically and modularly modified chemokine analogues.

    Science.gov (United States)

    Dong, Chang-Zhi; Tian, Shaomin; Choi, Won-Tak; Kumar, Santhosh; Liu, Dongxiang; Xu, Yan; Han, Xiaofeng; Huang, Ziwei; An, Jing

    2012-07-31

    The replication of human immunodeficiency virus type 1 (HIV-1) can be profoundly inhibited by the natural ligands of two major HIV-1 coreceptors, CXCR4 and CCR5. Stromal cell-derived factor-1α (SDF-1α) is a natural ligand of CXCR4. We have recently developed a synthetic biology approach of using synthetically and modularly modified (SMM)-chemokines to dissect various aspects of the structure-function relationship of chemokines and their receptors. Here, we used this approach to design novel SMM-SDF-1α analogues containing unnatural N-methylated residues in the amino terminus to investigate whether the polypeptide main chain amide bonds in the N-terminus of SDF-1α play a role in SDF-1α signaling via CXCR4 and/or receptor internalization. The results show that SDF-1α analogues with a modified N-methylated main chain at position 2, 3, or 5 retain significant CXCR4 binding and yet completely lose signaling activities. Furthermore, a representative N-methylated analogue has been shown to be incapable of causing CXCR4 internalization. These results suggest that the ability of SDF-1α to activate CXCR4 signaling and internalization is dependent upon the main chain amide bonds in the N-terminus of SDF-1α. This study demonstrates the feasibility and value of applying a synthetic biology approach to chemically engineer natural proteins and peptide ligands as probes of important biological functions that are not addressed by other biological techniques.

  5. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Science.gov (United States)

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diab