WorldWideScience

Sample records for acid metabolism induction

  1. Are polyamines involved in the induction and regulation of the Crassulacean acid metabolism?

    Science.gov (United States)

    Morel, C; Villanueva, V R; Queiroz, O

    1980-10-01

    Leaves of plants with Crassulacean acid metabolism (CAM) were analyzed for variation in the content of polyamines in connection with the metabolism of malic acid in the dark and in the light, and with the induction of full-CAM activity. Under conditions (long days) resulting in extremely low CAM activity, young leaves of K. blossfeldiana have very low content in the polyamine-precursor arginine and in putrescine. The content in these two substances was increased dramatically by full-CAM induction with short days. During the course of the night/day cycle two peaks of putrescine content were observed in leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb performing full-CAM operation: a large increase occurs toward the end of the day and the first half of the night, and its kinetics corresponds to the increase in the rate of malic acid synthesis; another peak, very sharp, appears during the first hours of the day, concomitant with the time of release of malic acid from the vacuole into the cytoplasm. In the case of Bryophyllum daigremontianum Berger similar variations were observed for the content in spermidine. These results support the hypothesis that polyamines could be involved in countering the tendency toward acidification of the cytoplasm at those moments of CAM operation at which the local concentration of malic acid is increased (i.e., during active synthesis in the dark and during the efflux from the vacuole in the light).

  2. Photoperiodism and enzyme rhythms: Kinetic characteristics of the photoperiodic induction of Crassulacean acid metabolism.

    Science.gov (United States)

    Brulfert, J; Guerrier, D; Queiroz, O

    1975-01-01

    The effect of photoperiod on Crassulacean acid metabolism (CAM) in Kalanchoe blossfeldiana Poellniz, cv. Tom Thumb, has characteristics similar to its effect on flowering in this plant (although these two phenomena are not causally related). The photoperiodic control of CAM is based on (a) dependance on phytochrome, (b) an endogenous circadian rhythm of sensitivity to photoperiodic signals, (c) a balance between specific positive (increase in enzyme capacity) and negative (inhibitory substances) effects of the photoperiod. Variations in malate content, capacity of phosphoenolpyruvate (PEP) carboxylase, and capacity of CAM inhibitors in young leaves were measured under photoperiodic conditions noninductive for CAM and after transfer into photoperiodic conditions inductive for CAM. Essential characteristics of the photoperiodic induction of CAM are: 1) lag time for malate accumulation; 2) after-effect of the inductive photoperiod on the malate accumulation, on the increase in PEP carboxylase capacity, and on the decrease in the level of long-day produced inhibitors; final levels of malate, enzyme capacity and inhibitor are proportional to the number of inductive day-night cycles; 3) cireadian rhythm in PEP carboxylase capacity with a fixed phase under noninductive photoperiods and a continuously shifting phase under inductive photoperiods, after complex advancing and delaying transients. Kinetic similarities indicate that photoperiodic control of different physiological functions, namely, CAM and flowering, may be achieved through similar mechanisms. Preliminary results with species of Bryophyllum and Sedum support this hypothesis. Phase relationships suggest different degrees of coupling between endogenous enzymic rhythm and photoperiod, depending on whether the plants are under long days or short days.

  3. Identification and induction of cytochrome P450s involved in the metabolism of flavone-8-acetic acid in mice

    OpenAIRE

    Pham, Minh Hien; Rhinn, Hervé; Auzeil, Nicolas; Regazzetti, Anne; Harami, Djamel Eddine; Scherman, Daniel; Chabot, Guy G.

    2011-01-01

    The metabolism of flavone-8-acetic acid (FAA) has been hypothesized to be partly responsible for its potent anticancer activity in mice. The purpose of this study was to identify the mouse enzymes involved in FAA Phase I metabolism and evaluate their possible induction in vivo by FAA. Mouse microsomes metabolized FAA into 6 metabolites: 3′,4′-dihydrodiol-FAA, 5,6-epoxy-FAA, 4′-OH-FAA, 3′-OH-FAA, 3′,4′-epoxy-FAA and 6-OH-FAA. Using Cyp-specific inhibitors (furafylline, Cyp1a2; α-naphthoflavone...

  4. Photoperiodism and Crassulacean acid metabolism : II. Relations between leaf aging and photoperiod in Crassulacean acid metabolism induction.

    Science.gov (United States)

    Brulfert, J; Guerrier, D; Queiroz, O

    1982-05-01

    Measurements of net CO2 exchange, malate accumulation, properties and capacity of phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) in leaves of different ages of two short-day dependent Crassulacean acid metabolism (CAM) plants (Kalanchoe blossfeldiana v. Poelln. Tom thumb and K. velutina Welw.) show that, in both species: a) young leaves from plants grown under long days display a CO2 exchange pattern typical of C3 plants; b) leaf aging promotes CAM under long-day conditions; c) short-day treatment induces CAM in young leaves to a higher degree than aging under long days; d) at least in K. blossfeldiana, the PEPC form developed with leaf aging under long days and the enzyme form synthetized de novo in young leaves grown under short days were shown to have similar properties. Short days also promote CAM in older leaves though at a lesser extent than in young leaves: The result is that this photoperiodic treatment increases the general level of CAM performance by the whole plant. The physiological meaning of the control of PEPC capacity by photoperiodism could be to afford a precisely timed seasonal increase in CAM potentiality, enabling the plant to immediately optimize its response to the onset of drought periods.

  5. Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

    Science.gov (United States)

    D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

    2014-11-01

    Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

  6. Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, J.; Spriggs, D.; Imamura, K.; Stone, R.; Luebbers, R.; Kufe, D.

    1989-01-01

    The treatment of human HL-60 promyelocytic leukemia cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcripts. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNS mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase, A/sub 2/ blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B/sub 4/. In contrast, the cyclooxygenase metabolite prostaglandin E/sub 2/ inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B/sub 4/ and prostaglandin E/sub 2/.

  7. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  8. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

    Directory of Open Access Journals (Sweden)

    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  9. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  10. Induction of resistance to gray mold with benzothiadiazole modifies amino acid profile and increases proanthocyanidins in grape: primary versus secondary metabolism.

    Science.gov (United States)

    Iriti, Marcello; Rossoni, Mara; Borgo, Michele; Ferrara, Luigia; Faoro, Franco

    2005-11-16

    Field treatments of grapevine (cv. Merlot) with the plant activator benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by Botrytis cinerea. Both incidence and severity of the disease were reduced. The resistance was associated with an increase of total polyphenols in berry skins, in particular, the proanthocyanidin fraction, that increased up to 36%. The amino acid profile of leaves was also modified by treatments, particularly lysine, that augmented 4-fold. Other amino acids involved in resistance mechanisms to either biotic or abiotic stress increased as well. These results indicate that BTH treatments can be used to control gray mold, thereby limiting an excessive use of fungicides, and could be exploited to increase the content of micronutrients of high nutritional value, arising from both primary and secondary metabolisms.

  11. Bile Acid Metabolism and Signaling

    Science.gov (United States)

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  12. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.

    Directory of Open Access Journals (Sweden)

    Eleanor C Saunders

    2014-01-01

    Full Text Available Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13C-stable isotope resolved metabolomics and (2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

  13. Induction of drug-metabolizing enzymes: mechanisms and consequences

    Energy Technology Data Exchange (ETDEWEB)

    Okey, A.B.; Roberts, E.A.; Harper, P.A.; Denison, M.S.

    1986-04-01

    The activity of many enzymes that carry out biotransformation of drugs and environmental chemicals can be substantially increased by prior exposure of humans or animals to a wide variety of foreign chemicals. Increased enzyme activity is due to true enzyme induction mediated by increased synthesis of mRNAs which code for specific drug-metabolizing enzymes. Several species of cytochrome P-450 are inducible as are certain conjugating enzymes such as glutathione S-transferases, glucuronosyl transferases, and epoxide hydrolases. Induction of drug-metabolizing enzymes has been shown in several instances to alter the efficacy of some therapeutic agents. Induction of various species of cytochrome P-450 also is known to increase the rate at which potentially toxic reactive metabolic intermediates are formed from drugs or environmental chemicals. Overall, however, induction of drug-metabolizing enzymes appears to be a beneficial adaptive response for organisms living in a ''chemically-hostile'' world.48 references.

  14. Grr1p is required for transcriptional induction of amino acid permease genes and proper transcriptional regulation of genes in carbon metabolism of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Regenberg, Birgitte; Nielsen, Jens

    2005-01-01

    and a grr1 Delta strain and adding citrulline in the exponential phase. Whole-genome transcription analyses were performed on samples from each cultivation, both immediately before and 30 min after citrulline addition. Transcriptional induction of the AAP genes AGP1, BAP2, BAP3, DIP5, GNP1 and TAT1 is fully...

  15. [The participation of ethanol in induction of carbohydrates metabolism disturbances].

    Science.gov (United States)

    Orywal, Karolina; Jelski, Wojciech; Szmitkowski, Maciej

    2009-07-01

    Alcohol and products of its metabolism lead to impairment of many organs functions, what cause systemic and local carbohydrates metabolism disturbances. Abusing of alcohol induces changes in pancreatic digestive enzymes secretion, what contributes to development of chronic alcoholic pancreatitis. Alcohol can cause secondary diabetes, what is result of pancreatic beta-cells damage and is a risk factor for type 2 diabetes. Alcohol cause liver cells degeneration and induction of many metabolic disturbances especially carbohydrates.

  16. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Hao, Qin; Jørgensen, Henry Johs. Høgh

    2011-01-01

    Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by e...... metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.......Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated...... with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1a, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited...

  17. Novel metabolic pathways for linoleic and arachidonic acid metabolism.

    Science.gov (United States)

    Moghaddam, M; Motoba, K; Borhan, B; Pinot, F; Hammock, B D

    1996-08-13

    Mouse liver microsomes oxidized linoleic acid to form 9,10- or 12,13-epoxyoctadecenoate. These monoepoxides were subsequently hydrolyzed to their corresponding diols in the absence of the microsomal epoxide hydrolase inhibitor, 1,2-epoxy-3,3,3-trichloropropane. Furthermore, both 9,10- and 12,13-epoxyoctadecenoates were oxidized to diepoxyoctadecanoate at apparently identical rates by mouse liver microsomal P-450 epoxidation. Both epoxyoctadecanoates and diepoxyoctadecanoates were converted to tetrahydrofuran-diols by microsomes. Tetrahydroxides of linoleate were produced as minor metabolites. Arachidonic acid was metabolized to epoxyeicosatrienoates, dihydroxyeicosatrienoates, and monohydroxyeicosatetraenoates by the microsomes. Microsomes prepared from clofibrate (but not phenobarbital) -treated mice exhibited much higher production rates for epoxyeicosatrienoates and vic-dihydroxyeicosatrienoates. This indicated an induction of P-450 epoxygenase(s) and microsomal epoxide hydrolase in mice by clofibrate and not by phenobarbital. Incubation of synthetic epoxyeicosatrienoates with microsomes led to the production of diepoxyeicosadienoates. Among chemically generated diepoxyeicosadienoate isomers, three of them possessing adjacent diepoxides were hydrolyzed to their diol epoxides which cyclized to the corresponding tetrahydrofuran-diols by microsomes as well as soluble epoxide hydrolase at a much higher rate. Larger cyclic products from non-adjacent diepoxides were not observed. The results of our in vitro experiments suggest that linoleic and arachidonic acid can be metabolized to their tetrahydrofuran-diols by two consecutive microsomal cytochrome P-450 epoxidations followed by microsomal or soluble epoxide hydrolase catalyzed hydrolysis of the epoxides. Incubation experiments with the S-9 fractions indicate that the soluble epoxide hydrolase is more important in this conversion. This manuscript is the first report of techniques for the separation and

  18. Bile Acid Metabolism in Liver Pathobiology

    Science.gov (United States)

    Chiang, John Y. L.; Ferrell, Jessica M.

    2018-01-01

    Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders. PMID:29325602

  19. Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.

    Science.gov (United States)

    McGrane, Ian R; Loveland, Joshua G; de Leon, Jose

    2017-01-01

    Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.

  20. Intestinal metabolism of sulfur amino acids

    Science.gov (United States)

    The gastrointestinal tract (GIT) is a metabolically significant site of sulfur amino acid (SAA) metabolism in the body and metabolizes approx. 20% of the dietary methionine intake that is mainly transmethylated to homocysteine and transsulfurated to cysteine. The GIT accounts for approx. 25% of the ...

  1. Intestinal transport and metabolism of bile acids

    Science.gov (United States)

    Dawson, Paul A.; Karpen, Saul J.

    2015-01-01

    In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic pathways. Signaling via these pathways will vary depending on the tissue and the concentration and chemical structure of the bile acid species. Important determinants of the size and composition of the bile acid pool are their efficient enterohepatic recirculation, their host and microbial metabolism, and the homeostatic feedback mechanisms connecting hepatocytes, enterocytes, and the luminal microbiota. This review focuses on the mammalian intestine, discussing the physiology of bile acid transport, the metabolism of bile acids in the gut, and new developments in our understanding of how intestinal metabolism, particularly by the gut microbiota, affects bile acid signaling. PMID:25210150

  2. Induction of autophagy by ARHI (DIRAS3) alters fundamental metabolic pathways in ovarian cancer models

    International Nuclear Information System (INIS)

    Ornelas, Argentina; McCullough, Christopher R.; Lu, Zhen; Zacharias, Niki M.; Kelderhouse, Lindsay E.; Gray, Joshua; Yang, Hailing; Engel, Brian J.; Wang, Yan; Mao, Weiqun; Sutton, Margie N.; Bhattacharya, Pratip K.; Bast, Robert C. Jr.; Millward, Steven W.

    2016-01-01

    Autophagy is a bulk catabolic process that modulates tumorigenesis, therapeutic resistance, and dormancy. The tumor suppressor ARHI (DIRAS3) is a potent inducer of autophagy and its expression results in necroptotic cell death in vitro and tumor dormancy in vivo. ARHI is down-regulated or lost in over 60 % of primary ovarian tumors yet is dramatically up-regulated in metastatic disease. The metabolic changes that occur during ARHI induction and their role in modulating death and dormancy are unknown. We employed Nuclear Magnetic Resonance (NMR)-based metabolomic strategies to characterize changes in key metabolic pathways in both cell culture and xenograft models of ARHI expression and autophagy. These pathways were further interrogated by cell-based immunofluorescence imaging, tracer uptake studies, targeted metabolic inhibition, and in vivo PET/CT imaging. Induction of ARHI in cell culture models resulted in an autophagy-dependent increase in lactate production along with increased glucose uptake and enhanced sensitivity to glycolytic inhibitors. Increased uptake of glutamine was also dependent on autophagy and dramatically sensitized cultured ARHI-expressing ovarian cancer cell lines to glutaminase inhibition. Induction of ARHI resulted in a reduction in mitochondrial respiration, decreased mitochondrial membrane potential, and decreased Tom20 staining suggesting an ARHI-dependent loss of mitochondrial function. ARHI induction in mouse xenograft models resulted in an increase in free amino acids, a transient increase in [ 18 F]-FDG uptake, and significantly altered choline metabolism. ARHI expression has previously been shown to trigger autophagy-associated necroptosis in cell culture. In this study, we have demonstrated that ARHI expression results in decreased cellular ATP/ADP, increased oxidative stress, and decreased mitochondrial function. While this bioenergetic shock is consistent with programmed necrosis, our data indicates that the accompanying up

  3. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  4. Amino acid metabolism conflicts with protein diversity

    OpenAIRE

    Krick, Teresa; Shub, David A.; Verstraete, Nina; Ferreiro, Diego U.; Alonso, Leonardo G.; Shub, Michael; Sanchez, Ignacio E.

    2014-01-01

    The 20 protein-coding amino acids are found in proteomes with different relative abundances. The most abundant amino acid, leucine, is nearly an order of magnitude more prevalent than the least abundant amino acid, cysteine. Amino acid metabolic costs differ similarly, constraining their incorporation into proteins. On the other hand, a diverse set of protein sequences is necessary to build functional proteomes. Here, we present a simple model for a cost-diversity trade-off postulating that n...

  5. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  6. Renal transport and metabolism of nicotinic acid

    International Nuclear Information System (INIS)

    Schuette, S.; Rose, R.C.

    1986-01-01

    Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

  7. Phylogenomic reconstruction of archaeal fatty acid metabolism

    Science.gov (United States)

    Dibrova, Daria V.; Galperin, Michael Y.; Mulkidjanian, Armen Y.

    2014-01-01

    While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analyzing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial-type β-oxidation of fatty acids (acyl-CoA-dehydrogenase, enoyl-CoA hydratase, and 3-hydroxyacyl-CoA dehydrogenase) with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three β-oxidation enzymes working in the reverse direction could potentially catalyze biosynthesis of fatty acids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase, and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications. PMID:24818264

  8. Regulation of uric acid metabolism and excretion.

    Science.gov (United States)

    Maiuolo, Jessica; Oppedisano, Francesca; Gratteri, Santo; Muscoli, Carolina; Mollace, Vincenzo

    2016-06-15

    Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology of platelets, muscles and neurotransmission. All cells require a balanced quantity of purines for growth, proliferation and survival. Under physiological conditions the enzymes involved in the purine metabolism maintain in the cell a balanced ratio between their synthesis and degradation. In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid, generated from the metabolism of purines, has been proven to play emerging roles in human disease. In fact the increase of serum uric acid is inversely associated with disease severity and especially with cardiovascular disease states. This review describes the enzymatic pathways involved in the degradation of purines, getting into their structure and biochemistry until the uric acid formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

  9. [Acid-base homeostasis: metabolic acidosis and metabolic alkalosis].

    Science.gov (United States)

    Dussol, Bertrand

    2014-07-01

    Acid-base homeostasis ensured by the kidneys, which maintain the equilibrium between proton generation by cellular metabolism and proton excretion in urine. This requirement is lifesaving because of the protons' ability to bind to anionic proteins in the extracellular space, modifying their structure and functions. The kidneys also regenerate bicarbonates. The kidney is not the sole organ in charge of maintaining blood pH in a very narrow range; lungs are also involved since they allow a large amount of volatile acid generated by cellular respiration to be eliminated. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  10. Ethosuximide: liver enzyme induction and D-glucaric acid excretion.

    Science.gov (United States)

    Gilbert, J C; Scott, A K; Galloway, D B; Petrie, J C

    1974-06-01

    1 A study has been carried out to determine if ethosuximide induces liver enzymes. 2 Ethosuximide did not affect the urinary excretion of D-glucaric acid by healthy adult subjects nor was the mean daily D-glucaric acid excretion of three epileptic children on long term ethosuximide therapy different from that of three matched controls. 3 Ethosuximide (10 mg/kg or 50 mg/kg daily) did not influence D-glucaric acid excretion or liver microsomal protein and cytochrome P450 contents of guinea pigs but at a dose of 100 mg/kg daily in rats it increased liver microsomal protein and cytochrome P450 without altering D-glucaric acid excretion. 4 These results suggest that at anticonvulsant doses ethosuximide is unlikely to induce liver enzymes. The precise relationship between D-glucaric acid excretion and liver enzyme induction remains in doubt.

  11. Transcriptome Analysis in Haematococcus pluvialis: Astaxanthin Induction by Salicylic Acid (SA) and Jasmonic Acid (JA).

    Science.gov (United States)

    Gao, Zhengquan; Li, Yan; Wu, Guanxun; Li, Guoqiang; Sun, Haifeng; Deng, Suzhen; Shen, Yicheng; Chen, Guoqiang; Zhang, Ruihao; Meng, Chunxiao; Zhang, Xiaowen

    2015-01-01

    Haematococcus pluvialis is an astaxanthin-rich microalga that can increase its astaxanthin production by salicylic acid (SA) or jasmonic acid (JA) induction. The genetic transcriptome details of astaxanthin biosynthesis were analyzed by exposing the algal cells to 25 mg/L of SA and JA for 1, 6 and 24 hours, plus to the control (no stress). Based on the RNA-seq analysis, 56,077 unigenes (51.7%) were identified with functions in response to the hormone stress. The top five identified subcategories were cell, cellular process, intracellular, catalytic activity and cytoplasm, which possessed 5600 (~9.99%), 5302 (~9.45%), 5242 (~9.35%), 4407 (~7.86%) and 4195 (~7.48%) unigenes, respectively. Furthermore, 59 unigenes were identified and assigned to 26 putative transcription factors (TFs), including 12 plant-specific TFs. They were likely associated with astaxanthin biosynthesis in Haematococcus upon SA and JA stress. In comparison, the up-regulation of differential expressed genes occurred much earlier, with higher transcript levels in the JA treatment (about 6 h later) than in the SA treatment (beyond 24 h). These results provide valuable information for directing metabolic engineering efforts to improve astaxanthin biosynthesis in H. pluvialis.

  12. Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis1

    Science.gov (United States)

    Traw, M. Brian; Bergelson, Joy

    2003-01-01

    Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332

  13. Dietary fatty acid metabolism in prediabetes.

    Science.gov (United States)

    Noll, Christophe; Carpentier, André C

    2017-02-01

    Experimental evidences are strong for a role of long-chain saturated fatty acids in the development of insulin resistance and type 2 diabetes. Ectopic accretion of triglycerides in lean organs is a characteristic of prediabetes and type 2 diabetes and has been linked to end-organ complications. The contribution of disordered dietary fatty acid (DFA) metabolism to lean organ overexposure and lipotoxicity is still unclear, however. DFA metabolism is very complex and very difficult to study in vivo in humans. We have recently developed a novel imaging method using PET with oral administration of 14-R,S-F-fluoro-6-thia-heptadecanoic acid (FTHA) to quantify organ-specific DFA partitioning. Our studies thus far confirmed impaired storage of DFA per volume of fat mass in abdominal adipose tissues of individuals with prediabetes. They also highlighted the increased channeling of DFA toward the heart, associated with subclinical reduction in cardiac systolic and diastolic function in individuals with prediabetes. In the present review, we summarize previous work on DFA metabolism in healthy and prediabetic states and discuss these in the light of our novel findings using PET imaging of DFA metabolism. We herein provide an integrated view of abnormal organ-specific DFA partitioning in prediabetes in humans.

  14. Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder

    Science.gov (United States)

    Moe, Orson W.

    2014-01-01

    Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. PMID:25045326

  15. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  16. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2012-01-01

    Full Text Available Obesity, diabetes, and metabolic syndromes are increasingly recognized as health concerns worldwide. Overnutrition and insulin resistance are the major causes of diabetic hyperglycemia and hyperlipidemia in humans. Studies in the past decade provide evidence that bile acids are not just biological detergents facilitating gut nutrient absorption, but also important metabolic regulators of glucose and lipid homeostasis. Pharmacological alteration of bile acid metabolism or bile acid signaling pathways such as using bile acid receptor agonists or bile acid binding resins may be a promising therapeutic strategy for the treatment of obesity and diabetes. On the other hand, bile acid signaling is complex, and the molecular mechanisms mediating the bile acid effects are still not completely understood. This paper will summarize recent advances in our understanding of bile acid signaling in regulation of glucose and lipid metabolism, and the potentials of developing novel therapeutic strategies that target bile acid metabolism for the treatment of metabolic disorders.

  17. Brain docosahexaenoic acid uptake and metabolism.

    Science.gov (United States)

    Lacombe, R J Scott; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-02-08

    Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the brain where it serves to regulate several important processes and, in addition, serves as a precursor to bioactive mediators. Given that the capacity of the brain to synthesize DHA locally is appreciably low, the uptake of DHA from circulating lipid pools is essential to maintaining homeostatic levels. Although, several plasma pools have been proposed to supply the brain with DHA, recent evidence suggests non-esterified-DHA and lysophosphatidylcholine-DHA are the primary sources. The uptake of DHA into the brain appears to be regulated by a number of complementary pathways associated with the activation and metabolism of DHA, and may provide mechanisms for enrichment of DHA within the brain. Following entry into the brain, DHA is esterified into and recycled amongst membrane phospholipids contributing the distribution of DHA in brain phospholipids. During neurotransmission and following brain injury, DHA is released from membrane phospholipids and converted to bioactive mediators which regulate signaling pathways important to synaptogenesis, cell survival, and neuroinflammation, and may be relevant to treating neurological diseases. In the present review, we provide a comprehensive overview of brain DHA metabolism, encompassing many of the pathways and key enzymatic regulators governing brain DHA uptake and metabolism. In addition, we focus on the release of non-esterified DHA and subsequent production of bioactive mediators and the evidence of their proposed activity within the brain. We also provide a brief review of the evidence from post-mortem brain analyses investigating DHA levels in the context of neurological disease and mood disorder, highlighting the current disparities within the field. Copyright © 2017. Published by Elsevier Ltd.

  18. Effect of abscisic acid on the linoleic acid metabolism in developing maize embryos

    International Nuclear Information System (INIS)

    Abian, J.; Gelpi, E.; Pages, M.

    1991-01-01

    Partially purified protein extracts from maize (Zea mays L.) embryos, whether treated or not with abscisic acid (ABA), were incubated with linoleic acid (LA) and 1-[ 14 C]LA. The resulting LA metabolites were monitored by high performance liquid chromatography with a radioactivity detector and identified by gas chromatography-mass spectrometry. α- and γ-ketol metabolites arising from 9-lipoxygenase activity were the more abundant compounds detected in the incubates, although the corresponding metabolites produced by 13-lipoxygenase were also present in the samples. In addition, a group of stereoisomers originating form two isomeric trihydroxy acids (9,12,13-trihydroxy-10-octadecenoic and 9,10,13-trihydroxy-11-octadecenoic acids) are described. Important variations in the relative proportions of the LA metabolites were observed depending on the embryo developmental stage and on ABA treatment. Two new ABA-induced compounds have been detected. These compounds are present in embryos at all developmental stages, being more abundant in old (60 days) embryos. Furthermore, ABA induction of these compounds is maximum at very young development stages, decreasing as maturation progresses. A tentative structure for these compounds (10-oxo-9,13-dihydroxy-11-octadecenoic acid and 12-oxo-9,13-dihydroxy-10-octadecenoic acid) is also provided. This study revealed an early stage in maize embryogenesis characterized by a higher relative sensitivity to ABA. The physiological importance of ABA on LA metabolism is discussed

  19. Metabolism of Mevalonic Acid in Vegetative and Induced Plants of Xanthium strumarium.

    Science.gov (United States)

    Bledsoe, C S

    1978-11-01

    The metabolism of mevalonic acid in Xanthium strumarium L. Chicago plants was studied to determine how mevalonate was metabolized and whether metabolism was related to induction of flowering. Leaves of vegetative, photoperiodically induced, and chemically inhibited cocklebur plants were supplied with [(14)C]mevalonic acid prior to or during a 16-hour inductive dark period. Vegetative, induced, and Tris(2-diethylaminoethyl)phosphate trihydrochloride-treated plants did not differ significantly in the amount of [(14)C]mevalonic acid they absorbed, nor in the distribution of radioactivity among the leaf blade (97%), petiole (2.3%), or shoot tip (0.7%). [(14)C]Mevalonic acid was rapidly metabolized and transported out of the leaves. Possible metabolites of mevalonate were mevalonic acid phosphates and sterols. No detectable (14)C was found in gibberellins, carotenoids, or the phytol alcohol of chlorophyll. Chemically inhibited plants accumulated (14)C compounds not found in vegetative or induced plants. When ethanol extracts of leaves, petioles, and buds were chromatographed, comparisons of chromatographic patterns did not show significant differences between vegetative and induced treatments.

  20. Metabolism of Mevalonic Acid in Vegetative and Induced Plants of Xanthium strumarium 1

    Science.gov (United States)

    Bledsoe, Caroline S.; Ross, Cleon W.

    1978-01-01

    The metabolism of mevalonic acid in Xanthium strumarium L. Chicago plants was studied to determine how mevalonate was metabolized and whether metabolism was related to induction of flowering. Leaves of vegetative, photoperiodically induced, and chemically inhibited cocklebur plants were supplied with [14C]mevalonic acid prior to or during a 16-hour inductive dark period. Vegetative, induced, and Tris(2-diethylaminoethyl)phosphate trihydrochloride-treated plants did not differ significantly in the amount of [14C]mevalonic acid they absorbed, nor in the distribution of radioactivity among the leaf blade (97%), petiole (2.3%), or shoot tip (0.7%). [14C]Mevalonic acid was rapidly metabolized and transported out of the leaves. Possible metabolites of mevalonate were mevalonic acid phosphates and sterols. No detectable 14C was found in gibberellins, carotenoids, or the phytol alcohol of chlorophyll. Chemically inhibited plants accumulated 14C compounds not found in vegetative or induced plants. When ethanol extracts of leaves, petioles, and buds were chromatographed, comparisons of chromatographic patterns did not show significant differences between vegetative and induced treatments. ImagesFig. 1 PMID:16660583

  1. Soybean Aphid Infestation Induces Changes in Fatty Acid Metabolism in Soybean.

    Directory of Open Access Journals (Sweden)

    Charles Kanobe

    Full Text Available The soybean aphid (Aphis glycines Matsumura is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fatty acids play in jasmonate-induced plant defenses, we analyzed the fatty acid profile of soybean leaves and seeds from aphid-infested plants. Aphid infestation reduced levels of polyunsaturated fatty acids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fatty acids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fatty acid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fatty acids, linolenic acid, is the precursor of jasmonate; thus, these changes in fatty acid metabolism may be examples of "metabolic hijacking" by the aphid to avoid the induction of effective defenses. Based on the changes in fatty acid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fatty acid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fatty acids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor.

  2. Inter-Kingdom Modification of Metabolic Behavior: [GAR+] Prion Induction in Saccharomyces cerevisiae Mediated by Wine Ecosystem Bacteria

    Directory of Open Access Journals (Sweden)

    Linda F Bisson

    2016-11-01

    Full Text Available The yeast Saccharomyces cerevisiae has evolved to dominate grape juice fermentation. A suite of cellular properties, rapid nutrient depletion, production of inhibitory compounds and the metabolic narrowing of the niche, all enable a minor resident of the initial population to dramatically increase its relative biomass in the ecosystem. This dominance of the grape juice environment is fueled by a rapid launch of glycolysis and energy generation mediated by transport of hexoses and an efficient coupling of transport and catabolism. Fermentation occurs in the presence of molecular oxygen as the choice between respiratory or fermentative growth is regulated by the availability of sugar a phenomenon known as glucose or catabolite repression. Induction of the GAR+ prion alters the expression of the major hexose transporter active under these conditions, Hxt3, reducing glycolytic capacity. Bacteria present in the grape juice ecosystem were able to induce the GAR+ prion in wine strains of S. cerevisiae. This induction reduced fermentation capacity but did not block it entirely. However, dominance factors such as the rapid depletion of amino acids and other nitrogen sources from the environment were impeded enabling greater access to these substrates for the bacteria. Bacteria associated with arrested commercial wine fermentations were able to induce the prion state, and yeast cells isolated from arrested commercial fermentations were found to be GAR+ thus confirming the ecological relevance of prion induction. Subsequent analyses demonstrated that the presence of environmental acetic acid could lead to GAR+ induction in yeast strains under certain conditions. The induction of the prion enabled yeast growth on non-preferred substrates, oxidation and reduction products of glucose and fructose, present as a consequence of bacterial energy production. In native ecosystems prion induction never exceeded roughly 50-60% of the population of yeast cells

  3. Cyclooxygenase-2 induction in macrophages is modulated by docosahexaenoic acid via interactions with free fatty acid receptor 4 (FFA4).

    Science.gov (United States)

    Li, Xinzhi; Yu, Ying; Funk, Colin D

    2013-12-01

    Cyclooxygenase-2 (COX-2)-derived prostaglandins are implicated in numerous inflammatory disorders. The purpose of these studies was to examine previously unexplored interactions between COX-2 induction and docosahexaenoic acid (DHA) via the free fatty acid receptor 4 (FFA4) signaling pathway in murine RAW 264.7 cells and peritoneal macrophages challenged with lipopolysaccharide (LPS). DHA dose (IC50=18 μM)- and time-dependently reduced COX-2 expression, without affecting COX-1. DHA (25 μM for 24 h) decreased LPS-induced prostaglandin E2 (PGE2) synthesis by 81%, primarily through reducing COX-2 (60%), as well as down-regulating microsomal prostaglandin E synthase-1 (46%), but independently of peroxisome proliferator-activated receptors. FFA4 knockdown abrogated DHA effects on COX-2 induction, PGE2 production, and interleukin 6 (IL-6) gene expression. In the presence of inhibitors of eicosanoid metabolism via COX-2, 12/15-lipoxygenase and CYP450s (rofecoxib (1 μM), PD146176 (2 μM), or MS-PPOH (20 μM)), DHA was still effective in attenuating COX-2 induction. Moreover, Toll-like receptor 4 signaling via Akt/JNK phosphorylation and p65 nuclear translocation was repressed by DHA-activated FFA4 coupling with β-arrestin 2, which was reversed by FFA4 knockdown. These data support DHA modulation of COX-2 expression and activity, in part, via FFA4, which provides a new mechanistic explanation for some of the anti-inflammatory effects of DHA.

  4. Engineering microbial fatty acid metabolism for biofuels and biochemicals

    DEFF Research Database (Denmark)

    Marella, Eko Roy; Holkenbrink, Carina; Siewers, Verena

    2017-01-01

    microbial catalysis. This review summarizes the recent advances in the engineering of microbial metabolism for production of fatty acid-derived products. We highlight the efforts in engineering the central carbon metabolism, redox metabolism, controlling the chain length of the products, and obtaining...

  5. Radioiodinated free fatty acids; can we measure myocardial metabolism

    International Nuclear Information System (INIS)

    Visser, F.C.; Eenige, M.J. van; Duwel, C.M.B.; Roos, J.P.

    1986-01-01

    To investigate the feasibility of radioiodinated free fatty acids for ''metabolic imaging'', the kinetics and distribution pattern of metabolites of heptadecanoic acid I 131 (HDA I 131) were studied in canine myocardium throughout metabolic interventions. In control dogs and in dogs during glucose/insulin and sodium lactate infusion, biopsy specimens were taken during a go-min period after HDA I 131 administration and analyzed. Clearly distinct patterns of distribution and elimination were seen during the metabolic interventions, indicating the usefulness of iodinated fatty acids for metabolic studies. (orig.)

  6. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  7. Bile Acid Signaling in Metabolic Disease and Drug Therapy

    Science.gov (United States)

    Li, Tiangang

    2014-01-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

  8. 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.

  9. The Role of Microbial Amino Acid Metabolism in Host Metabolism

    OpenAIRE

    Evelien P. J. G. Neis; Cornelis H. C. Dejong; Sander S. Rensen

    2015-01-01

    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 protei...

  10. Disturbed amino acid metabolism in HIV: association with neuropsychiatric symptoms

    Directory of Open Access Journals (Sweden)

    Johanna M Gostner

    2015-07-01

    Full Text Available Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1-infected patients. Both essential amino acids, tryptophan and phenylalanine are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms such as development of depression, fatigue, and cognitive impairment.Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions.

  11. The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Norshalizah Mamikutty

    2014-01-01

    Full Text Available Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome.

  12. Dietary effects on fatty acid metabolism of common carp.

    Science.gov (United States)

    Csengeri, I

    1996-01-01

    The paper summarises experimental data demonstrating effects of various dietary factors exerting changes in the fatty acid composition and fatty acid metabolism of the common carp (Cyprinus carpio L.). Among the dietary factors (1) supplementary feeding in fish ponds, (2) absence of essential fatty acids (EFA) in the diet, (3) starvation, and (4) ration level were studied. It was concluded that supplementary feeding in carp rearing ponds is frequently excessive in the Hungarian carp culture practice, inducing slight EFA-deficiency and enhancing de novo fatty acid synthesis. This latter caused enlarged fat depots with high oleic acid contents in the fish organs and tissues. EFA-deficient diets enhanced the synthesis of oleic acid except when high rate of de novo fatty acid synthesis was suppressed by dietary fatty acids. Feeding EFA-deficient diets caused gradual decrease in the levels of polyunsaturated fatty acids and gradual increase in that of Mead's acid: 20:3(n-9), an indicator of the EFA-deficiency. At prolonged starvation, polyunsaturated fatty acids of the structural lipids were somehow protected and mainly oleic acid was utilised for energy production. At high ration levels, excessive exogenous polyunsaturates were decomposed, and probably converted to oleic acid or energy. Starvation subsequent to the feeding the fish at various ration levels, reflected adaptive changes in the fatty acid metabolism: Below and above the ration level required for the most efficient feed utilisation for growth, decomposition processes of the fatty acid metabolism were accelerated.

  13. Metabolism of amino acid amides in Pseudomonas putida ATCC 12633

    NARCIS (Netherlands)

    Hermes, H.F.M.; Croes, L.M.; Peeters, W.P.H.; Peters, P.J.H.; Dijkhuizen, L.

    1993-01-01

    The metabolism of the natural amino acid L-valine, the unnatural amino acids D-valine, and D-, L-phenylglycine (D-, L-PG), and the unnatural amino acid amides D-, L-phenylglycine amide (D, L-PG-NH2) and L-valine amide (L-Val-NH2) was studied in Pseudomonas putida ATCC 12633. The organism possessed

  14. Dependence of the metabolic fecal amino acids on the amino acid content of the feed. 2

    International Nuclear Information System (INIS)

    Krawielitzki, K.; Schadereit, R.; Voelker, T.; Reichel, K.

    1982-01-01

    In an experiment with 20 15 N-labelled growing rats the excretion of amino acids as well as of metabolic fecal amino acids were investigated after feeding of soybean oil meal as sole protein source. A low, yet statistically significant increase of the excretion of amino acids and metabolic fecal amino acids was ascertained in accordance with a growing quota of soybean oil meal in the ration. The true digestibility of amino acids ascertained according to conventional methods is above 90% and, under consideration of the increase of metabolic fecal amino acids, on the average increases by 3.5 digestibility units (1.4 to 6.2). (author)

  15. Acid stress response and protein induction in Campylobacter jejuni isolates with different acid tolerance

    DEFF Research Database (Denmark)

    Birk, Tina; Wik, Monica Takamiya; Lametsch, René

    2012-01-01

    with MALDI-TOF-TOF. The most acid-sensitive isolate was C. jejuni 327, followed by NCTC 11168 and isolate 305 as the most tolerant. Overall, induction of five proteins was observed within the pI range investigated: 19 kDa periplasmic protein (p19), thioredoxin-disulfide (TrxB), a hypothetical protein Cj0706......RT-PCR. In this transcriptomic analysis, only up-regulation of trxB and p19 was observed. CONCLUSIONS: A defined medium that supports the growth of a range of Campylobacter strains and suitable for proteomic analysis was developed. Mainly proteins normally involved in iron control and oxidative stress defence were induced...

  16. Ecophysiology of Crassulacean Acid Metabolism (CAM).

    Science.gov (United States)

    Lüttge, Ulrich

    2004-06-01

    Crassulacean Acid Metabolism (CAM) as an ecophysiological modification of photosynthetic carbon acquisition has been reviewed extensively before. Cell biology, enzymology and the flow of carbon along various pathways and through various cellular compartments have been well documented and discussed. The present attempt at reviewing CAM once again tries to use a different approach, considering a wide range of inputs, receivers and outputs. Input is given by a network of environmental parameters. Six major ones, CO(2), H(2)O, light, temperature, nutrients and salinity, are considered in detail, which allows discussion of the effects of these factors, and combinations thereof, at the individual plant level ('physiological aut-ecology'). Receivers of the environmental cues are the plant types genotypes and phenotypes, the latter including morphotypes and physiotypes. CAM genotypes largely remain 'black boxes', and research endeavours of genomics, producing mutants and following molecular phylogeny, are just beginning. There is no special development of CAM morphotypes except for a strong tendency for leaf or stem succulence with large cells with big vacuoles and often, but not always, special water storage tissues. Various CAM physiotypes with differing degrees of CAM expression are well characterized. Output is the shaping of habitats, ecosystems and communities by CAM. A number of systems are briefly surveyed, namely aquatic systems, deserts, salinas, savannas, restingas, various types of forests, inselbergs and paramós. While quantitative census data for CAM diversity and biomass are largely missing, intuition suggests that the larger CAM domains are those systems which are governed by a network of interacting stress factors requiring versatile responses and not systems where a single stress factor strongly prevails. CAM is noted to be a strategy for variable, flexible and plastic niche occupation rather than lush productivity. 'Physiological syn-ecology' reveals

  17. Metabolic strategies of beer spoilage lactic acid bacteria in beer.

    Science.gov (United States)

    Geissler, Andreas J; Behr, Jürgen; von Kamp, Kristina; Vogel, Rudi F

    2016-01-04

    Beer contains only limited amounts of readily fermentable carbohydrates and amino acids. Beer spoilage lactic acid bacteria (LAB) have to come up with metabolic strategies in order to deal with selective nutrient content, high energy demand of hop tolerance mechanisms and a low pH. The metabolism of 26 LAB strains of 6 species and varying spoilage potentialwas investigated in order to define and compare their metabolic capabilities using multivariate statistics and outline possible metabolic strategies. Metabolic capabilities of beer spoilage LAB regarding carbohydrate and amino acids did not correlate with spoilage potential, but with fermentation type (heterofermentative/homofermentative) and species. A shift to mixed acid fermentation by homofermentative (hof) Pediococcus claussenii and Lactobacillus backii was observed as a specific feature of their growth in beer. For heterofermentative (hef) LAB a mostly versatile carbohydrate metabolism could be demonstrated, supplementing the known relevance of organic acids for their growth in beer. For hef LAB a distinct amino acid metabolism, resulting in biogenic amine production, was observed, presumably contributing to energy supply and pH homeostasis.

  18. Amino acid metabolism in plant leaf, 1

    International Nuclear Information System (INIS)

    Ito, Osamu; Kumazawa, Kikuo

    1977-01-01

    14C-labelled sodium bicarbonate and 15N-labelled ammonium sulfate were simultaneously vacuum-infiltrated into detached sunflower leaves, and the incorporation of 14C and 15N into free amino acids was chased during 60-min period in the light and in the dark. In the light, the 14C specific activity of aspartic acid, alanine, serine and glycine rapidly increased for 5 min and thereafter decreased. On the other hand, that of glutamic acid continued to increase slowly during the entire 60-min period. In the dark, aspartic acid most actively incorporated 14C. The difference of changes in 14C specific activity between glutamic acid and other amino acids was also observed in the dark as in the light. These results suggest that the carbon skeleton of glutamic acid is synthesized from aspartic acid, alanine, serine and glycine. 15N content of glutamine was the highest of all amino acids investigated in the light, and it was followed by glutamic acid, alanine, aspartic acid, serine and glycine, in this order. In the dark, 15N content of glutamic acid fell remarkably and was lower than that of alanine up to 5 min. From these 15N tracer experiments, it is suggested that the incorporation of ammonium into glutamic acid is strictly dependent on light and that alanine incorporates ammonium by the direct animation besides the transamination from glutamic acid. (auth.)

  19. Production of amino acids - Genetic and metabolic engineering approaches.

    Science.gov (United States)

    Lee, Jin-Ho; Wendisch, Volker F

    2017-12-01

    The biotechnological production of amino acids occurs at the million-ton scale and annually about 6milliontons of l-glutamate and l-lysine are produced by Escherichia coli and Corynebacterium glutamicum strains. l-glutamate and l-lysine production from starch hydrolysates and molasses is very efficient and access to alternative carbon sources and new products has been enabled by metabolic engineering. This review focusses on genetic and metabolic engineering of amino acid producing strains. In particular, rational approaches involving modulation of transcriptional regulators, regulons, and attenuators will be discussed. To address current limitations of metabolic engineering, this article gives insights on recent systems metabolic engineering approaches based on functional tools and method such as genome reduction, amino acid sensors based on transcriptional regulators and riboswitches, CRISPR interference, small regulatory RNAs, DNA scaffolding, and optogenetic control, and discusses future prospects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Specific fatty acids as metabolic modulators in the dairy cow

    Directory of Open Access Journals (Sweden)

    J.A.A. Pires

    2008-07-01

    Full Text Available This review summarizes recent developments on the utilization of specific fatty acids to modulate bovine energy metabolism, with emphasis on the periparturient dairy cow. A number of experiments have assessed the effects of polyunsaturated fatty acids on bovine hepatic energy metabolism using in vitro and in vivo models. Treatment of hepatocytes with specific fatty acids altered energy metabolism in vitro. For example, linolenic acid seemed to decrease hepatocyte triacylglycerol accumulation. This effect was confirmed in vivo, using parenteral infusions of emulsions derived from different fat sources to feed-restricted non-lactating cows. Additionally, polyunsaturated fatty acids can increase whole body response to insulin, potentially enhancing antilipolytic effects of insulin and muscle protein anabolism in the bovine. There is limited literature on the effects of feeding fat sources rich in omega-3 polyunsaturated fatty acids, such as fish oil and linseed oil, on metabolism of periparturient dairy cows. Available research has yielded conflicting results which need further clarification. On the other hand, specific isomers of conjugated linoleic acid consistently induce milk fat depression and are able to decrease energy export in milk by periparturient dairy cows. Nonetheless, research is still needed to assess whether these effects will ultimately benefit productivity and health status of periparturient dairy cows. Limitations of available methods to protect fatty acids from ruminal biohydrogenation are also addressed.

  1. Salicylic Acid Alters Antioxidant and Phenolics Metabolism in ...

    African Journals Online (AJOL)

    Key words: Antioxidant enzymes; Catharanthus roseus; indole alkaloids; phenolic metabolism; salicylic acid; salinity stress. Abbreviations: CAT - catalase; Chl - chlorophyll; Car - carotenoids; DTNB - 5,5-dithiobis-2-nitrobenzoic acid; GR - glutathione reductase; GST - Glutathione-S-transferase; H2O2 - hydrogen peroxide; ...

  2. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    DEFF Research Database (Denmark)

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation....

  3. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

    Science.gov (United States)

    Castro, Maite A; Beltrán, Felipe A; Brauchi, Sebastián; Concha, Ilona I

    2009-07-01

    In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD(+)/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.

  4. Exogenous fatty acid metabolism in bacteria.

    Science.gov (United States)

    Yao, Jiangwei; Rock, Charles O

    2017-10-01

    Bacterial type II fatty acid synthesis (FASII) is a target for novel antibiotic development. All bacteria encode for mechanisms to incorporate exogenous fatty acids, and some bacteria can use exogenous fatty acids to bypass FASII inhibition. Bacteria encode three different mechanisms for activating exogenous fatty acids for incorporation into phospholipid synthesis. Exogenous fatty acids are converted into acyl-CoA in Gammaproteobacteria such as E. coli. Acyl-CoA molecules constitute a separate pool from endogenously synthesized acyl-ACP. Acyl-CoA can be used for phospholipid synthesis or broken down by β-oxidation, but cannot be used for lipopolysaccharide synthesis. Exogenous fatty acids are converted into acyl-ACP in some Gram-negative bacteria. The resulting acyl-ACP undergoes the same fates as endogenously synthesized acyl-ACP. Exogenous fatty acids are converted into acyl-phosphates in Gram-positive bacteria, and can be used for phospholipid synthesis or become acyl-ACP. Only the order Lactobacillales can use exogenous fatty acids to bypass FASII inhibition. FASII shuts down completely in presence of exogenous fatty acids in Lactobacillales, allowing Lactobacillales to synthesize phospholipids entirely from exogenous fatty acids. Inhibition of FASII cannot be bypassed in other bacteria because FASII is only partially down-regulated in presence of exogenous fatty acid or FASII is required to synthesize essential metabolites such as β-hydroxyacyl-ACP. Certain selective pressures such as FASII inhibition or growth in biofilms can select for naturally occurring one step mutations that attenuate endogenous fatty acid synthesis. Although attempts have been made to estimate the natural prevalence of these mutants, culture-independent metagenomic methods would provide a better estimate. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  5. Pathophysiological aspect of metabolic acid-base disorders

    Directory of Open Access Journals (Sweden)

    Nešović-Ostojić Jelena

    2016-01-01

    Full Text Available Maintaing the arterial pH values (in normal range of 7,35-7,45 is one of the main principles of homeostasis. Regulatory responses, including chemical buffering (extracellular, intracellular, sceletal, the regulation of pCO2 by the respiratory system, and the regulation of [HCO3-] by the kidneys, act in concert to maintain normal arterial pH value. The main extracellular chemical buffer is bicarbonate-carbonic acid buffer system. The kidneys contribute to the regulation of hydrogen (and bicarbonate in body fluids in two ways. Proximal tubules are important in bicarbonate reabsorption and distal tubules excrete hydrogen ion (as ammonium ion or titratable acid. There are four simple acid-base disorders: metabolic acidosis and metabolic alkalosis; respiratory acidosis and respiratory alkalosis. Metabolic acidosis can occur because of an increase in endogenous acid production (such as lactate and ketoacids, loss of bicarbonate (as in diarrhea, or accumulation of endogenous acids (as in renal failure. Metabolic acidosis can also be with high and normal (hyperchloremic metabolic acidosis anion gap. Renal tubular acidosis (RTA is a form of hyperchloremic metabolic acidosis which occurs when the renal damage primarily affects tubular function. The main problem in distal RTA is reduced H+ excretion in distal tubule. Type 2 RTA is also called proximal RTA because the main problem is greatly impaired reabsorption of bicarbonate in proximal tubule. Impaired cation exchange in distal tubule is the main problem in RTA type 4. Metabolic alkalosis occurs as a result of net gain of [HCO3-] or loss of nonvolatile acid from extracellular fluids. Metabolic alkalosis can be associated with reduced or increased extracellular volume.

  6. Fatty acid metabolism in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    van Roermund, C. W. T.; Waterham, H. R.; IJlst, L.; Wanders, R. J. A.

    2003-01-01

    Peroxisomes are essential subcellular organelles involved in a variety of metabolic processes. Their importance is underlined by the identification of a large group of inherited diseases in humans in which one or more of the peroxisomal functions are impaired. The yeast Saccharomyces cerevisiae has

  7. Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.

    Science.gov (United States)

    Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J

    2017-01-01

    Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia. We evaluated 103 patients less than 40 years of age, from a low-income population, and without history of cardiovascular disease, in all of them the presence of metabolic syndrome was assessed in accordance with the International Diabetes Federation criteria. In all patients, fasting serum uric acid levels were measured; hyperuricaemia was defined as serum uric acid values 6.5 mg/dl in men and 5.1 mg/dl in women. Statistical analysis was performed with odds ratio. 83 of our patients (80.5%) suffered metabolic syndrome, the odds ratio for the presence of metabolic syndrome in patients with hyperuricaemia was 5.1 (p=0.002, I.C 1.8- 14.5). When patients were evaluated by gender a significantly association between hyperuricaemia and metabolic syndrome was found in women (odds ratio 3.6, p=0.048, C.I. 1.0-12.9), and men (odds ratio 10.2, p= 0.015, IC 1.5-13.2). When uric acid was correlated with the components of metabolic syndrome, we only found a positive correlation with waist circumference (r=0.483). Our results showed a significant association between hyperuricemia and metabolic syndrome in low-income young adults in Mexico. DR is associated with estimated risk of CVD in type 2 diabetic patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Biobased organic acids production by metabolically engineered microorganisms

    DEFF Research Database (Denmark)

    Chen, Yun; Nielsen, Jens

    2016-01-01

    Bio-based production of organic acids via microbial fermentation has been traditionally used in food industry. With the recent desire to develop more sustainable bioprocesses for production of fuels, chemicals and materials, the market for microbial production of organic acids has been further...... expanded as organic acids constitute a key group among top building block chemicals that can be produced from renewable resources. Here we review the current status for production of citric acid and lactic acid, and we highlight the use of modern metabolic engineering technologies to develop high...... performance microbes for production of succinic acid and 3-hydroxypropionic acid. Also, the key limitations and challenges in microbial organic acids production are discussed...

  9. Nucleotide Metabolism and its Control in Lactic Acid Bacteria

    DEFF Research Database (Denmark)

    Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal

    2005-01-01

    Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...... the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria....

  10. Bile acid metabolism and signaling in cholestasis, inflammation and cancer

    Science.gov (United States)

    Apte, Udayan

    2015-01-01

    Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles in bile acid synthesis. Bile acids are physiological detergent molecules, so are highly cytotoxic. They undergo enterohepatic circulation and play important roles in generating bile flow and facilitating biliary secretion of endogenous metabolites and xenobiotics and intestinal absorption of dietary fats and lipid soluble vitamins. Bile acid synthesis, transport and pool size are therefore tightly regulated under physiological conditions. In cholestasis, impaired bile flow leads to accumulation of bile acids in the liver, causing hepatocyte and biliary injury and inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis and eventually liver failure. Chronic cholestasis also increases the risk of developing hepatocellular or cholangiocellular carcinomas. Extensive research in the last two decades has shown that bile acids act as signaling molecules that regulate various cellular processes. The bile acid-activated nuclear receptors are ligand-activated transcriptional factors that play critical roles in the regulation of bile acid, drug and xenobiotic metabolism. In cholestasis, these bile acid-activated receptors regulate a network of genes involved in bile acid synthesis, conjugation, transport and metabolism to alleviate bile acid-induced inflammation and injury. Additionally, bile acids are known to regulate cell growth and proliferation, and altered bile acid levels in diseased conditions have been implicated in liver injury/regeneration and tumorigenesis. We will cover the mechanisms that regulate bile acid homeostasis and detoxification during cholestasis, and the roles of bile acids in the initiation and regulation of hepatic inflammation, regeneration and carcinogenesis. PMID:26233910

  11. Attenuation of abnormalities in the lipid metabolism during experimental myocardial infarction induced by isoproterenol in rats: beneficial effect of ferulic acid and ascorbic acid.

    Science.gov (United States)

    Yogeeta, Surinder Kumar; Hanumantra, Rao Balaji Raghavendran; Gnanapragasam, Arunachalam; Senthilkumar, Subramanian; Subhashini, Rajakannu; Devaki, Thiruvengadam

    2006-05-01

    The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.

  12. Treatment of Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... of amino acids. Babies with TYR I may need vitamin D, a vitamin that can help babies who ... Rickets is a condition in which too little vitamin D causes a child’s bones to be ... condition, he may need to take certain medicines. For example: Babies with ...

  13. Amino acid metabolism of Lemna minor L

    International Nuclear Information System (INIS)

    Rhodes, D.; Rich, P.J.; Brunk, D.G.

    1989-01-01

    A serious limitation to the use of N(O,S)-heptafluorobutyryl isobutyl amino acid derivatives in the analysis of 15 N-labeling kinetics of amino acids in plant tissues, is that the amides glutamine and asparagine undergo acid hydrolysis to glutamate and aspartate, respectively, during derivatization. This led us to consider an alternative procedure for derivatization of glutamine and asparagine with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide in pyridine. Gas chromatography-mass spectrometry yielded fragment ions (M-57) of mass 417 and 431 for the [ 14 N]asparagine and [ 14 N]glutamine derivatives, respectively, suitable for monitoring unlabeled, single- 15 N- and double- 15 N-labeled amide species from the ion clusters at mass to charge ratio (m/z) 415 to 423 for asparagine, and m/z 429 to 437 for glutamine. From separate analyses of the specific isotope abundance of the amino-N groups of asparagine and glutamine as their N-heptafluorobutyryl isobutyl derivatives, the specific amide-[ 15 N] abundance of these amino acids was determined

  14. N-13 labeled amino acids: biodistribution, metabolism and dosimetric considerations

    International Nuclear Information System (INIS)

    Rosenspire, K.C.; Gelbard, A.S.

    1986-01-01

    With the growing interest in metabolic imaging and with the increasing number of cyclotron/PET facilities, more studies are being performed in animal and humans using short-lived positron-emitting radionuclides. Amino acids labeled either with N-13 or C-11 are one group of compounds being used to study in vivo regional organ (i.e., brain and heart) or tumor metabolism. Of the studies previously reported using C-11 or N-13 labeled amino acids (methionine, alanine, valine, glutamate, glutamine and tryptophan), imaging was restricted mainly to the organ or tissue of interest with little information obtained about the whole-bode distribution of the label. Such data are important for studying interorgan transport of amino acids and for determining accurate dosimetric measurements after intravenous injection of labeled amino acids. The goals of the authors study were to compare the distribution of several N-13 L-amino acids and N-13 ammonia in tumor-bearing mice and to determine the metabolic fate of the label in vivo. The following amino acids were enzymatically labeled using N-13 ammonia: glutamine, glutamate, methionine, α-aminobutyric acid, valine and leucine. 30 references, 2 figures, 14 tables

  15. Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

    Science.gov (United States)

    Sorrell, T C; Muller, M; Sztelma, K

    1992-05-01

    Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

  16. Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Sun, J.D.; MacGregor, J.T.; Wehr, C.M.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

    1990-01-01

    Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased

  17. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.

    Science.gov (United States)

    Mueller, Michaela; Thorell, Anders; Claudel, Thierry; Jha, Pooja; Koefeler, Harald; Lackner, Carolin; Hoesel, Bastian; Fauler, Guenter; Stojakovic, Tatjana; Einarsson, Curt; Marschall, Hanns-Ulrich; Trauner, Michael

    2015-06-01

    Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to bariatric surgery. Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7α-hydroxylase induction mirrored by elevated C4 and 7α-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

    DEFF Research Database (Denmark)

    Mourtzakis, Marina; Saltin, B.; Graham, T.

    2006-01-01

    During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline...... amino acid taken up during exercise and recovery. Alanine and glutamine were also associated...... with pyruvate metabolism, and they comprised 68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism...

  19. A Review of the Metabolic Origins of Milk Fatty Acids

    Directory of Open Access Journals (Sweden)

    Anamaria COZMA

    2013-08-01

    Full Text Available Milk fat and its fatty acid profile are important determinants of the technological, sensorial, and nutritional properties of milk and dairy products. The two major processes contributing to the presence of fatty acids in ruminant milk are the mammary lipogenesis and the lipid metabolism in the rumen. Among fatty acids, 4:0 to 12:0, almost all 14:0 and about a half of 16:0 in milk fat derive from de novo synthesis within the mammary gland. De novo synthesis utilizes as precursors acetate and butyrate produced through carbohydrates ruminal fermentation and involves acetyl-CoA carboxylase and fatty acid synthetase as key enzymes. The rest of 16:0 and all of the long-chain fatty acids derive from mammary uptake of circulating lipoproteins and nonesterified fatty acids that originate from digestive absorption of lipids and body fat mobilization. Further, long-chain fatty acids as well as medium-chain fatty acids entering the mammary gland can be desaturated via Δ-9 desaturase, an enzyme that acts by adding a cis-9-double bond on the fatty acid chain. Moreover, ruminal biohydrogenation of dietary unsaturated fatty acids results in the formation of numerous fatty acids available for incorporation into milk fat. Ruminal biohydrogenation is performed by rumen microbial population as a means of protection against the toxic effects of polyunsaturated fatty acids. Within the rumen microorganisms, bacteria are principally responsible for ruminal biohydrogenation when compared to protozoa and anaerobic fungi.

  20. Induction of DNA damage by oxidised amino acids and proteins

    DEFF Research Database (Denmark)

    Luxford, Catherine; Dean, Roger T; Davies, Michael Jonathan

    2002-01-01

    Exposure of amino acids, peptides and proteins to radicals in the presence of O2 generates hydroperoxides in a dose-dependent manner. These hydroperoxides are stable in the absence of exogenous catalysts (e.g. heat, light, redox-active transition metal ions), but decompose rapidly in the presence...

  1. Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis.

    Science.gov (United States)

    Oh, Euhlim; Lu, Mingshou; Park, Changhun; Park, Changhun; Oh, Han Bin; Lee, Sang Yup; Lee, Jinwon

    2011-02-01

    A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/ MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

  2. Induction of secondary metabolism of Aspergillus terreus ATCC 20542 in the batch bioreactor cultures.

    Science.gov (United States)

    Boruta, Tomasz; Bizukojc, Marcin

    2016-04-01

    Cultivation of Aspergillus terreus ATCC 20542 in a stirred tank bioreactor was performed to induce the biosynthesis of secondary metabolites and provide the bioprocess-related insights into the metabolic capabilities of the investigated strain. The activation of biosynthetic routes was attempted by the diversification of process conditions and growth media. Several strategies were tested, including the addition of rapeseed oil or inulin, changing the concentration of nitrogen source, reduction of chlorine supply, cultivation under saline conditions, and using various aeration schemes. Fifteen secondary metabolites were identified in the course of the study by using ultra-high performance liquid chromatography coupled with mass spectrometry, namely mevinolinic acid, 4a,5-dihydromevinolinic acid, 3α-hydroxy-3,5-dihydromonacolin L acid, terrein, aspulvinone E, dihydroisoflavipucine, (+)-geodin, (+)-bisdechlorogeodin, (+)-erdin, asterric acid, butyrolactone I, desmethylsulochrin, questin, sulochrin, and demethylasterric acid. The study also presents the collection of mass spectra that can serve as a resource for future experiments. The growth in a salt-rich environment turned out to be strongly inhibitory for secondary metabolism and the formation of dense and compact pellets was observed. Generally, the addition of inulin, reducing the oxygen supply, and increasing the content of nitrogen source did not enhance the production of examined molecules. The most successful strategy involved the addition of rapeseed oil to the chlorine-deficient medium. Under these conditions, the highest levels of butyrolactone I, asterric acid, and mevinolinic acid were achieved and the presence of desmethylsulochrin and (+)-bisdechlorogeodin was detected in the broth. The constant and relatively high aeration rate in the idiophase was shown to be beneficial for terrein and (+)-geodin biosynthesis.

  3. Plants know where it hurts: root and shoot jasmonic acid induction elicit differential responses in Brassica oleracea.

    Directory of Open Access Journals (Sweden)

    Tom O G Tytgat

    Full Text Available Plants respond to herbivore attack by rapidly inducing defenses that are mainly regulated by jasmonic acid (JA. Due to the systemic nature of induced defenses, attack by root herbivores can also result in a shoot response and vice versa, causing interactions between above- and belowground herbivores. However, little is known about the molecular mechanisms underlying these interactions. We investigated whether plants respond differently when roots or shoots are induced. We mimicked herbivore attack by applying JA to the roots or shoots of Brassica oleracea and analyzed molecular and chemical responses in both organs. In shoots, an immediate and massive change in primary and secondary metabolism was observed. In roots, the JA-induced response was less extensive and qualitatively different from that in the shoots. Strikingly, in both roots and shoots we also observed differential responses in primary metabolism, development as well as defense specific traits depending on whether the JA induction had been below- or aboveground. We conclude that the JA response is not only tissue-specific but also dependent on the organ that was induced. Already very early in the JA signaling pathway the differential response was observed. This indicates that both organs have a different JA signaling cascade, and that the signal eliciting systemic responses contains information about the site of induction, thus providing plants with a mechanism to tailor their responses specifically to the organ that is damaged.

  4. Hepatocyte heterogeneity in the metabolism of amino acids and ammonia

    NARCIS (Netherlands)

    Häussinger, D.; Lamers, W. H.; Moorman, A. F.

    1992-01-01

    With respect to hepatocyte heterogeneity in ammonia and amino acid metabolism, two different patterns of sublobular gene expression are distinguished: 'gradient-type' and 'strict- or compartment-type' zonation. An example for strict-type zonation is the reciprocal distribution of carbamoylphosphate

  5. Photoperiodism and crassulacean acid metabolism : I. Immunological and kinetic evidences for different patterns of phosphoenolpyruvate carboxylase isoforms in photoperiodically inducible and non-inducible Crassulacean acid metabolism plants.

    Science.gov (United States)

    Brulfert, J; Müller, D; Kluge, M; Queiroz, O

    1982-05-01

    Plants of Kalanchoe blossfeldiana v. Poelln. Tom Thumb and Sedum morganianum E. Walth. were grown under controlled photoperiodic conditions under either short or long days. Gaz exchange measurements confirmed that in K. blossfeldiana Crassulacean acid metabolism (CAM) was photoperiodically inducible and that S. morganianum performed CAM independently of photoperiod. With K. blossfeldiana, a comparison of catalytic and regulatory properties of phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) from short-day and long-day grown plants showed differences, but not with S. morganianum. Ouchterlony double diffusion tests and immunotitration experiments (using a S. morganianum PEPC antibody) established that CAM is induced in K. blossfeldiana-but not in S. morganianum-through the synthesis of a new PEPC isoform; this form shows an immunological behavior different from that prevailing under non-inductive conditions and can be considered as specific for CAM performance.

  6. PARIS reprograms glucose metabolism by HIF-1α induction in dopaminergic neurodegeneration.

    Science.gov (United States)

    Kang, Hojin; Jo, Areum; Kim, Hyein; Khang, Rin; Lee, Ji-Yeong; Kim, Hanna; Park, Chi-Hu; Choi, Jeong-Yun; Lee, Yunjong; Shin, Joo-Ho

    2018-01-22

    Our previous study found that PARIS (ZNF746) transcriptionally suppressed transketolase (TKT), a key enzyme in pentose phosphate pathway (PPP) in the substantia nigra (SN) of AAV-PARIS injected mice. In this study, we revealed that PARIS overexpression reprogrammed glucose metabolic pathway, leading to the increment of glycolytic proteins along with TKT reduction in the SN of AAV-PARIS injected mice. Knock-down of TKT in differentiated SH-SY5Y cells led to an increase of glycolytic enzymes and decrease of PPP-related enzymes whereas overexpression of TKT restored PARIS-mediated glucose metabolic shift, suggesting that glucose metabolic alteration by PARIS is TKT-dependent. Inhibition of PPP by either PARIS overexpression or TKT knock-down elevated the level of H 2 O 2 , and diminished NADPH and GSH levels, ultimately triggering the induction of HIF-1α, a master activator of glycolysis. In addition, TKT inhibition by stereotaxic injection of oxythiamine demonstrated slight decrement of dopaminergic neurons (DNs) in SN but not cortical neurons in the cortex, suggesting that TKT might be a survival factor of DNs. In differentiated SH-SY5Y, cell toxicity by GFP-PARIS was partially restored by introduction of Flag-TKT and siRNA-HIF-1α. We also observed the increase of HIF-1α and glycolytic hexokinase 2 in the SN of Parkinson's disease patients. Taken together, these results suggest that PARIS accumulation might distort the balance of glucose metabolism, providing clues for understanding mechanism underlying selective DNs death by PARIS. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Metabolically engineered cells for the production of polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    2005-01-01

    The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves...... improvement of the PUFA content in the host organism through fermentation optimization, e.g. decreasing the temperature and/or designing an optimal medium, or through improving the flux towards fatty acids by metabolic engineering, e.g. through over-expression of fatty acid synthases, over-expression of other...

  8. Nickel deficiency disrupts metabolism of ureides, amino acids, and organic acids of young pecan foliage.

    Science.gov (United States)

    Bai, Cheng; Reilly, Charles C; Wood, Bruce W

    2006-02-01

    The existence of nickel (Ni) deficiency is becoming increasingly apparent in crops, especially for ureide-transporting woody perennials, but its physiological role is poorly understood. We evaluated the concentrations of ureides, amino acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni-S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch). Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but total ureides, urea concentration, and urease activity were reduced. Disruption of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine, valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids, and lower concentrations of histidine and glutamic acid. Ni deficiency also disrupted the citric acid cycle, the second stage of respiration, where Ni-D foliage contained very low levels of citrate compared to Ni-S foliage. Disruption of carbon metabolism was also via accumulation of lactic and oxalic acids. The results indicate that mouse-ear, a key morphological symptom, is likely linked to the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and margins of leaflets. Our results support the role of Ni as an essential plant nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan is evidence of the existence of unidentified physiological roles for Ni in pecan.

  9. Homocysteine regulates fatty acid and lipid metabolism in yeast.

    Science.gov (United States)

    Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O; Wolinski, Heimo; Rechberger, Gerald N; Tehlivets, Oksana

    2018-04-13

    S -Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S -adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Evolution of amino acid metabolism inferred through cladistic analysis.

    Science.gov (United States)

    Cunchillos, Chomin; Lecointre, Guillaume

    2003-11-28

    Because free amino acids were most probably available in primitive abiotic environments, their metabolism is likely to have provided some of the very first metabolic pathways of life. What were the first enzymatic reactions to emerge? A cladistic analysis of metabolic pathways of the 16 aliphatic amino acids and 2 portions of the Krebs cycle was performed using four criteria of homology. The analysis is not based on sequence comparisons but, rather, on coding similarities in enzyme properties. The properties used are shared specific enzymatic activity, shared enzymatic function without substrate specificity, shared coenzymes, and shared functional family. The tree shows that the earliest pathways to emerge are not portions of the Krebs cycle but metabolisms of aspartate, asparagine, glutamate, and glutamine. The views of Horowitz (Horowitz, N. H. (1945) Proc. Natl. Acad. Sci. U. S. A. 31, 153-157) and Cordón (Cordón, F. (1990) Tratado Evolucionista de Biologia, Aguilar, Madrid, Spain), according to which the upstream reactions in the catabolic pathways and the downstream reactions in the anabolic pathways are the earliest in evolution, are globally corroborated; however, with some exceptions. These are due to later opportunistic connections of pathways (actually already suggested by these authors). Earliest enzymatic functions are mostly catabolic; they were deaminations, transaminations, and decarboxylations. From the consensus tree we extracted four time spans for amino acid metabolism development. For some amino acids catabolism and biosynthesis occurred at the same time (Asp, Glu, Lys, Leu, Ala, Val, Ile, Pro, Arg). For others ultimate reactions that use amino acids as a substrate or as a product are distinct in time, with catabolism preceding anabolism for Asn, Gln, and Cys and anabolism preceding catabolism for Ser, Met, and Thr. Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.

  11. Postillumination burst of carbon dioxide in crassalacean Acid metabolism plants.

    Science.gov (United States)

    Crews, C E; Vines, H M; Black, C C

    1975-04-01

    Immediately following exposure to light, a postillumination burst of CO(2) has been detected in Crassulacean acid metabolism plants. A detailed study with pineapple (Ananas comosus) leaves indicates that the postillumination burst changes its amplitude and kinetics during the course of a day. In air, the postillumination burst in pineapple leaves generally is exhibited as two peaks. The postillumination burst is sensitive to atmospheric CO(2) and O(2) concentrations as well as to the light intensity under which plants are grown. We propose that the CO(2) released in the first postillumination burst peak is indicative of photorespiration since it is sensitive to either O(2) or CO(2) concentration while the second CO(2) evolution peak is likely due to decarboxylation of organic acids involved in Crassulacean acid metabolism.In marked contrast to other higher plants, the postillumination burst in Crassulacean acid metabolism plants can be equal to or greater than the rate of photosynthesis. Photosynthesis in pineapple leaves also varies throughout a day. Both photosynthesis and the postillumination burst have a daily variation which apparently is a complex function of degree of leaf acidity, growth light intensity, ambient gas phase, and the time a plant has been exposed to a given gas.

  12. Metabolic evolution of Escherichia coli strains that produce organic acids

    Science.gov (United States)

    Grabar, Tammy; Gong, Wei; Yocum, R Rogers

    2014-10-28

    This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.

  13. Metabolism of sialic acid by Bifidobacterium breve UCC2003.

    Science.gov (United States)

    Egan, Muireann; O'Connell Motherway, Mary; Ventura, Marco; van Sinderen, Douwe

    2014-07-01

    Bifidobacteria constitute a specific group of commensal bacteria that inhabit the gastrointestinal tracts of humans and other mammals. Bifidobacterium breve UCC2003 has previously been shown to utilize several plant-derived carbohydrates that include cellodextrins, starch, and galactan. In the present study, we investigated the ability of this strain to utilize the mucin- and human milk oligosaccharide (HMO)-derived carbohydrate sialic acid. Using a combination of transcriptomic and functional genomic approaches, we identified a gene cluster dedicated to the uptake and metabolism of sialic acid. Furthermore, we demonstrate that B. breve UCC2003 can cross feed on sialic acid derived from the metabolism of 3'-sialyllactose, an abundant HMO, by another infant gut bifidobacterial strain, Bifidobacterium bifidum PRL2010. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. Metabolism of Sialic Acid by Bifidobacterium breve UCC2003

    Science.gov (United States)

    Egan, Muireann; O'Connell Motherway, Mary; Ventura, Marco

    2014-01-01

    Bifidobacteria constitute a specific group of commensal bacteria that inhabit the gastrointestinal tracts of humans and other mammals. Bifidobacterium breve UCC2003 has previously been shown to utilize several plant-derived carbohydrates that include cellodextrins, starch, and galactan. In the present study, we investigated the ability of this strain to utilize the mucin- and human milk oligosaccharide (HMO)-derived carbohydrate sialic acid. Using a combination of transcriptomic and functional genomic approaches, we identified a gene cluster dedicated to the uptake and metabolism of sialic acid. Furthermore, we demonstrate that B. breve UCC2003 can cross feed on sialic acid derived from the metabolism of 3′-sialyllactose, an abundant HMO, by another infant gut bifidobacterial strain, Bifidobacterium bifidum PRL2010. PMID:24814790

  15. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    International Nuclear Information System (INIS)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-01-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production

  16. Regulation of intestinal protein metabolism by amino acids.

    Science.gov (United States)

    Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

    2013-09-01

    Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

  17. ω-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Chen, Yi; Xu, Chengfu; Yan, Tianlian; Yu, Chaohui; Li, Youming

    2015-01-01

    The aim of this study was to evaluate the effect of ω-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as ω-3 fatty acids were used as intervention. The autophagic role of ω-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of ω-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. ω-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. ω-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. ω-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Heart and bile acids - Clinical consequences of altered bile acid metabolism.

    Science.gov (United States)

    Vasavan, Tharni; Ferraro, Elisa; Ibrahim, Effendi; Dixon, Peter; Gorelik, Julia; Williamson, Catherine

    2018-04-01

    Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Structurally modified fatty acids - clinical potential as tracers of metabolism

    International Nuclear Information System (INIS)

    Dudczak, R.; Schmoliner, R.; Angelberger, P.; Knapp, F.F.; Goodman, M.M.

    1985-01-01

    Recently 15-p-iodophenyl-betamethyl-pentadecanoic acid (BMPPA) was proposed for myocardial scintigraphy, as possible probe of metabolic processes other than β-oxidation. In 19 patients myocardial scintigraphy was done after i.v. BMPPA (2 to 4 mCi). Data were collected (LAO 45 0 /14; anterior/5) for 100 minutes in the fasted patients. From heart (H) and liver (L) organ to background (BG) ratios were calculated, and the elimination (E) behavior was analyzed from BG (V. cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl 3 /MeOH extraction of plasma samples (90 min. pi) both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with benzoic acid, BMPPA and triglycerides. In urine (0 to 2h pi: 4.1% dose) hippuric acid was found. It is concluded that BMPPA is a useful agent for myocardial scintigraphy. Its longer retention in the heart compared to unbranched radioiodinated fatty acids may facilitate SPECT studies. Rate of elimination and plasma analysis indicate the metabolic breakdown of BMPPA. Yet, the complexity of the supposed mechanism may impede curve interpretation in terms of specific metabolic pathways. 19 refs., 5 tabs

  20. Metabolic Conversion of l-Ascorbic Acid to Oxalic Acid in Oxalate-accumulating Plants 1

    Science.gov (United States)

    Yang, Joan C.; Loewus, Frank A.

    1975-01-01

    l-Ascorbic acid-1-14C and its oxidation product, dehydro-l-ascorbic acid, produced labeled oxalic acid in oxalate-accumulating plants such as spinach seedlings (Spinacia oleracea) and the detached leaves of woodsorrel (Oxalis stricta and O. oregana), shamrock (Oxalis adenopylla), and begonia (Begonia evansiana). In O. oregana, conversion occurred equally well in the presence or absence of light. This relationship between l-ascorbic acid metabolism and oxalic acid formation must be given careful consideration in attempts to explain oxalic accumulation in plants. PMID:16659288

  1. Metabolic Diet App Suite for inborn errors of amino acid metabolism.

    Science.gov (United States)

    Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

    2016-03-01

    An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright

  2. Chirality, phase transitions and their induction in amino acids

    International Nuclear Information System (INIS)

    Salam, A.

    1991-04-01

    ''Atoms such as carbon, oxygen, nitrogen and hydrogen, the major constituents of biological molecules, are less than 0.4 nm in diameter... The behaviour of small molecules is a reflection of the intrinsic properties of the constituent atoms. Hence it might be expected that the behaviour of large macromolecules can be explained by a knowledge of atomic properties. Since organelles, whole cells and organisms are essentially macromolecular assemblies, it may be possible in time to derive an atomic theory of life'' (Rees and Sternberg). It has been suggested that chirality among the twenty amino acids which make up the proteins may be a consequence of a phase transition which is analogous to that due to BCS superconductivity. We explore these ideas in this paper and show, following Lee and Drell, that a crucial form for the transition temperature T c involves dynamical symmetry breaking. The t-quarks or supersymmetry (or something similar which ensures a heavy mass) appear to be essential if such mechanisms are to hold. (author). 12 refs, 1 fig., 1 tab

  3. Metabolic inhibitors as stimulating factors for citric acid production

    International Nuclear Information System (INIS)

    Adham, N.Z.; Ahmed, E.M.; Refai, H.A.E.

    2008-01-01

    The effect of some metabolic inhibitors on citric acid (CA) production by Aspergillus niger in cane molasses medium was investigated. Addition of 0.01-0.1 mM iodoacetic acid and sodium arsenate, 0.05-1.0 mM sodium malonate, 0.01 mM sodium azide, 0.01-0.05 mM sodium fluoride, 0.1-1.0 mM EDTA stimulated CA production (5-49%). Higher concentrations (10 mM) of iodoacetic acid, sodium malonate and 0.5 mM sodium azide caused a complete inhibition of fungal growth, Iodoacetic acid, sodium arsenate and sodium fluoride (0.2 mM) caused a remarkable inhibition of CA production. The implications of those preliminary functions was discussed. (author)

  4. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel

    2016-01-01

    Full Text Available Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

  5. Regulation of abscisic acid metabolism in relation to the dormancy and germination of cereal grains

    Directory of Open Access Journals (Sweden)

    Justyna Fidler

    2015-03-01

    Full Text Available Seed dormancy is of particular importance in the cultivation of cereals, as it directly affects the quality of crop yield. If the dormancy period is too short, this may lead to pre-harvest sprouting, whereas a dormancy period that is too long may cause uneven germination; both of these scenarios are associated with economic losses. Most enzymes engaged in the metabolism of abscisic acid (ABA have been identified, and significant progress has been made in understanding the role of this phytohormone in the induction and maintenance of dormancy, mainly as a result of research conducted in Arabidopsis. Much less is known about the metabolism and function of ABA in cereal grains, especially in relation to dormancy and germination. This review focuses on the regulation of ABA metabolism in dormant and non-dormant cereal grains, in both the dry state and upon imbibition. Moreover, this review describes the influence of factors such as after-ripening, light, temperature, nitric oxide, and reactive oxygen species (ROS on the dormancy and germination of cereal grains. These factors, with the exception of ROS, appear to affect the level of dormancy and germination of grains through regulation of ABA metabolism.

  6. 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...

  7. Differential retinoic acid inhibition of ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate and by germicidal ultraviolet light

    International Nuclear Information System (INIS)

    Lichti, U.; Patterson, E.; Hennings, H.; Yuspa, S.H.

    1981-01-01

    Several retinoids including retinoic acid effectively inhibit phorbol ester-mediated tumor promotion and ornithine decarboxylase (ODC) induction in mouse epidermis. To understand better the possible cellular site of action of retinoids, the inhibitory action of retinoic acid on the induction of ODC was compared for two distinctly different inducers, namely, 12-O-tetradecanoylphorbol-13-acetate (TPA) and germicidal ultraviolet light (uv), in primary mouse epidermal cell cultures. It was found that the induction of ODC by TPA is almost completely prevented by retinoic acid while the induction by uv is only moderately inhibited. The differential inhibition of enzyme induction cannot be accounted for by selective retinoid inhibition of DNA, RNA, or protein synthesis either alone or in concert with TPA or uv. These agents possibly act at transcription or translation, both of which are required for ODC induction by TPA or uv

  8. 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

  9. Fatty acids in energy metabolism of the central nervous system.

    Science.gov (United States)

    Panov, Alexander; Orynbayeva, Zulfiya; Vavilin, Valentin; Lyakhovich, Vyacheslav

    2014-01-01

    In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

  10. RELATIONSHIP BETWEEN URIC ACID METABOLISM AND INSULIN RESISTANCE

    OpenAIRE

    辻本, 伸宏; 金内, 雅夫; 尾崎, 博基; 藤田, 泰三; 中嶋, 民夫; 土肥, 和紘

    1998-01-01

    To investigate the relationship between uric acid (UA) metabolism and insulin resistance, serum creatinine concentration (Scr), serum UA concentration (SuA) and the urinary excretion of creatinine and UA were determined in 25 non-diabetic patients. Creatinine clearance (Ccr) and UA clearance/creatinine clearance ratio (CuA/Ccr) were also calculated. Insulin resistance was evaluated by the euglycemic glucose clamp tech- nique and expressed as the mean value of the glucose infusion rate (M-valu...

  11. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

    Science.gov (United States)

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-01-01

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment. PMID:27570415

  12. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea.

    Science.gov (United States)

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-08-14

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

  13. Bacterial fatty acid metabolism in modern antibiotic discovery.

    Science.gov (United States)

    Yao, Jiangwei; Rock, Charles O

    2017-11-01

    Bacterial fatty acid synthesis is essential for many pathogens and different from the mammalian counterpart. These features make bacterial fatty acid synthesis a desirable target for antibiotic discovery. The structural divergence of the conserved enzymes and the presence of different isozymes catalyzing the same reactions in the pathway make bacterial fatty acid synthesis a narrow spectrum target rather than the traditional broad spectrum target. Furthermore, bacterial fatty acid synthesis inhibitors are single-targeting, rather than multi-targeting like traditional monotherapeutic, broad-spectrum antibiotics. The single-targeting nature of bacterial fatty acid synthesis inhibitors makes overcoming fast-developing, target-based resistance a necessary consideration for antibiotic development. Target-based resistance can be overcome through multi-targeting inhibitors, a cocktail of single-targeting inhibitors, or by making the single targeting inhibitor sufficiently high affinity through a pathogen selective approach such that target-based mutants are still susceptible to therapeutic concentrations of drug. Many of the pathogens requiring new antibiotic treatment options encode for essential bacterial fatty acid synthesis enzymes. This review will evaluate the most promising targets in bacterial fatty acid metabolism for antibiotic therapeutics development and review the potential and challenges in advancing each of these targets to the clinic and circumventing target-based resistance. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Induction of the metabolic regulator Txnip in fasting-induced and natural torpor.

    Science.gov (United States)

    Hand, Laura E; Saer, Ben R C; Hui, Simon T; Jinnah, Hyder A; Steinlechner, Stephan; Loudon, Andrew S I; Bechtold, David A

    2013-06-01

    Torpor is a physiological state characterized by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions. The hypothalamus coordinates energy homeostasis and thermoregulation and plays a key role in directing torpor. We recently showed that mice lacking the orphan G protein-coupled receptor Gpr50 readily enter torpor in response to fasting and have now used these mice to conduct a microarray analysis of hypothalamic gene expression changes related to the torpor state. This revealed a strong induction of thioredoxin-interacting protein (Txnip) in the hypothalamus of torpid mice, which was confirmed by quantitative RT-PCR and Western blot analyses. In situ hybridization identified the ependyma lining the third ventricle as the principal site of torpor-related expression of Txnip. To characterize further the relationship between Txnip and torpor, we profiled Txnip expression in mice during prolonged fasting, cold exposure, and 2-deoxyglucose-induced hypometabolism, as well as in naturally occurring torpor bouts in the Siberian hamster. Strikingly, pronounced up-regulation of Txnip expression was only observed in wild-type mice when driven into torpor and during torpor in the Siberian hamster. Increase of Txnip was not limited to the hypothalamus, with exaggerated expression in white adipose tissue, brown adipose tissue, and liver also demonstrated in torpid mice. Given the recent identification of Txnip as a molecular nutrient sensor important in the regulation of energy metabolism, our data suggest that elevated Txnip expression is critical to regulating energy expenditure and fuel use during the extreme hypometabolic state of torpor.

  15. Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach

    Directory of Open Access Journals (Sweden)

    Cidália Dionísio Pereira

    2014-01-01

    Full Text Available The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model. The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease.

  16. 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.

  17. Acylation and metabolism of (n-6) fatty acids in hepatocytes

    International Nuclear Information System (INIS)

    Voss, A.C.; Sprecher, H.

    1986-01-01

    Isolated hepatocytes (5 x 10 6 in 2ml) from chow fed rats were incubated from 20 to 60 min. with increasing concentrations of [1- 14 C] labeled 18:2 (n-6), 18:3 (n-6) or 20:3 (n-6) to define optimum conditions for measuring acylation and metabolism to other (n-6) acids with subsequent incorporation into lipids. The triglycerides (TG) and phospholipids (PL) contained 157 and 80 nmols of 18:2 (n-6) and 6.0 and 6.1 nmols of other (n-6) acids, respectively, when cells were incubated with 0.3mM [1- 14 C] 18:2 (n-6) for 40 min. When cells were incubated with 0.3mM [1- 14 C] 18:2 (n-6) plus 0.15 to 0.45mM 18:3 (n-6) or 20:3 (n-6), the metabolism of 18:2 (n-6) to other (n-6) acids was inhibited but not totally abolished. These results may suggest that (n-6) acid made from linoleate do not totally equilibrate with exogenous 18:3 (n-6) or 20:3

  18. Dietary fatty acids linking postprandial metabolic response and chronic diseases.

    Science.gov (United States)

    Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2012-01-01

    Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

  19. Hepatic Metabolism of Perfluorinated Carboxylic Acids and Polychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in vito

    Science.gov (United States)

    1994-01-06

    L. Narayanan. and B. M. Jamot. ’Effects of Peulluoro-n- octanoic Acid , Perfluoro-n-decanoic Acid , and Clofibrate on Hepatic Phosphorus Metabolism in...pathways and examined the impact of perfluorocarboxylic acid exposure. This investigative strategy will delineate the metabolic effices exerted by...Perfluorinated Carboxylic Acids and Polychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in Vivo Principal Investigator: Nicholas V. Reo

  20. Effect of aspartic acid and glutamate on metabolism and acid stress resistance of Acetobacter pasteurianus.

    Science.gov (United States)

    Yin, Haisong; Zhang, Renkuan; Xia, Menglei; Bai, Xiaolei; Mou, Jun; Zheng, Yu; Wang, Min

    2017-06-15

    Acetic acid bacteria (AAB) are widely applied in food, bioengineering and medicine fields. However, the acid stress at low pH conditions limits acetic acid fermentation efficiency and high concentration of vinegar production with AAB. Therefore, how to enhance resistance ability of the AAB remains as the major challenge. Amino acids play an important role in cell growth and cell survival under severe environment. However, until now the effects of amino acids on acetic fermentation and acid stress resistance of AAB have not been fully studied. In the present work the effects of amino acids on metabolism and acid stress resistance of Acetobacter pasteurianus were investigated. Cell growth, culturable cell counts, acetic acid production, acetic acid production rate and specific production rate of acetic acid of A. pasteurianus revealed an increase of 1.04, 5.43, 1.45, 3.30 and 0.79-folds by adding aspartic acid (Asp), and cell growth, culturable cell counts, acetic acid production and acetic acid production rate revealed an increase of 0.51, 0.72, 0.60 and 0.94-folds by adding glutamate (Glu), respectively. For a fully understanding of the biological mechanism, proteomic technology was carried out. The results showed that the strengthening mechanism mainly came from the following four aspects: (1) Enhancing the generation of pentose phosphates and NADPH for the synthesis of nucleic acid, fatty acids and glutathione (GSH) throughout pentose phosphate pathway. And GSH could protect bacteria from low pH, halide, oxidative stress and osmotic stress by maintaining the viability of cells through intracellular redox equilibrium; (2) Reinforcing deamination of amino acids to increase intracellular ammonia concentration to maintain stability of intracellular pH; (3) Enhancing nucleic acid synthesis and reparation of impaired DNA caused by acid stress damage; (4) Promoting unsaturated fatty acids synthesis and lipid transport, which resulted in the improvement of cytomembrane

  1. Effect of indole-3-butyric acid (IBA) on in vitro root induction in ...

    African Journals Online (AJOL)

    Root induction pre-developed in vitro plantlets of orchid was carried out using indole-3-butyric acid (IBA) (0, 0.5, 1.0, 1.5, 2.0, 2.5 and 3 mM) on basal Murashige and Skoog (MS) medium. Among the concentrations of IBA, the number of roots per plantlet with 1 mM IBA was found to be the highest (2.25 roots per plantlet) ...

  2. Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression.

    Science.gov (United States)

    Zeman, Miroslav; Vecka, Marek; Jáchymová, Marie; Jirák, Roman; Tvrzická, Eva; Stanková, Barbora; Zák, Ales

    2009-04-01

    The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54 Males/59 Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P phosphatidylcholine (PC) (P = 0.052), lower index of Delta5 desaturation (P insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.

  3. Dependence of the metabolic fecal amino acids on the amino acid content of the feed. 1

    International Nuclear Information System (INIS)

    Krawielitzki, K.; Schadereit, R.; Voelker, T.; Reichel, K.

    1981-01-01

    The amount of metabolic fecal amino acids (MFAA) in dependence on the amino acid intake was determined for graded maize rations in 15 N-labelled rats and the part of labelled endogenous amino acids in feces was calculated by the isotope dilution method. The excretion of amino acids and MFAA in feces are described as functions of the amino acid intake for 17 amino acids and calculated regressively. For all 17 amino acids investigated, there was a more or less steep increase of MFAA according to an increasing amino acid intake. In contrast to N-free feeding, the MFAA increase to the 2- to 4.5-fold value in feeding with pure maize (16.5% crude protein). The thesis of the constancy of the excretion of MFAA can consequently be no longer maintained. The true digestibility according to the conventional method is, on an average of all amino acids, 7.3 units below ascertained according to the 15 N method. The limiting amino acids lysine and threonine revealed the greatest difference. Tryptophane as first limiting amino acid could not be determined. The true digestibility of nearly all amino acids ascertained for maize by the isotope method is above 90%. (author)

  4. Effect of acute acid loading on acid-base and calcium metabolism

    DEFF Research Database (Denmark)

    Osther, Palle J

    2006-01-01

    OBJECTIVE: To investigate the acid-base and calcium metabolic responses to acute non-carbonic acid loading in idiopathic calcium stone-formers and healthy males using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h ammonium chloride loading studies were performed in 12...... male recurrent idiopathic calcium stone-formers and 12 matched healthy men using a randomized, placebo-controlled, cross-over design. Arterialized capillary blood, serum and urine were collected hourly for measurement of electrolytes, ionized calcium, magnesium, phosphate, parathyroid hormone and acid-base...... status. Concentrations of non-metabolizable base (NB) and acid (NA) were calculated from measured concentrations of non-metabolizable ions. RESULTS: The extracellular acid-base status in the stone-formers during basal conditions and acid loading was comparable to the levels in the healthy controls...

  5. Metabolism modifications and apoptosis induction after Cellfood™ administration to leukemia cell lines.

    Science.gov (United States)

    Catalani, Simona; Carbonaro, Valentina; Palma, Francesco; Arshakyan, Marselina; Galati, Rossella; Nuvoli, Barbara; Battistelli, Serafina; Canestrari, Franco; Benedetti, Serena

    2013-09-09

    Cellfood™ (CF) is a nutritional supplement containing deuterium sulphate, minerals, amino acids, and enzymes, with well documented antioxidant properties. Its organic and inorganic components are extracted from the red algae Lithothamnion calcareum, whose mineral extract has shown growth-inhibitory effect both on in vitro and in vivo models. The purpose of this study was to evaluate the antiproliferative effects of CF on leukemic cells. In fact, according to its capacity to modulate O2 availability and to improve mitochondrial respiratory metabolism, we wondered if CF could affect cancer cell metabolism making cells susceptible to apoptosis. Three leukemic cell lines, Jurkat, U937, and K562, were treated with CF 5 μl/ml up to 72 hours. Cell viability, apoptosis (i.e. caspase-3 activity and DNA fragmentation), hypoxia inducible factor 1 alpha (HIF-1α) concentration, glucose transporter 1 (GLUT-1) expression, lactate dehydrogenase (LDH) activity and lactate release in the culture medium were detected and compared with untreated cells. CF significantly inhibited leukemic cell viability by promoting cell apoptosis, as revealed by caspase-3 activation and DNA laddering. In particular, CF treated cells showed lower HIF-1α levels and lower GLUT-1 expression as compared to untreated cells. At the same time, CF was able to reduce LDH activity and, consequently, the amount of lactate released in the extracellular environment. We supplied evidence for an antiproliferative effect of CF on leukemia cell lines by inducing cell death through an apoptotic mechanism and by altering cancer cell metabolism through HIF-1α and GLUT-1 regulation. Thanks to its antioxidative and proapoptotic properties, CF might be a good candidate for cancer prevention.

  6. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment

    International Nuclear Information System (INIS)

    Billi de Catabbi, Silvia C.; Faletti, Alicia; Fuentes, Federico; San Martin de Viale, Leonor C.; Cochon, Adriana C.

    2005-01-01

    Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A 2 (cPLA 2 ) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg -1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA 2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA 2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA 2 in

  7. Metabolic engineering of lactic acid bacteria for the production of nutraceuticals

    NARCIS (Netherlands)

    Hugenholtz, J.; Sybesma, W.; Groot, M.N.; Wisselink, W.; Ladero, V.; Burgess, K.; Sinderen, van D.; Piard, J.C.; Eggink, G.; Smid, E.J.; Savoy, G.; Sesma, F.; Jansen, T.; Hols, P.; Kleerebezem, M.

    2002-01-01

    Lactic acid bacteria display a relatively simple and well-described metabolism where the sugar source is converted mainly to lactic acid. Here we will shortly describe metabolic engineering strategies on the level of sugar metabolism, that lead to either the efficient re-routing of the lactococcal

  8. Metabolic changes and induction of hepatic lipidosis during feed restriction in llamas.

    Science.gov (United States)

    Tornquist, S J; Cebra, C K; Van Saun, R J; Smith, B B; Mattoon, J S

    2001-07-01

    To determine whether feed restriction induces hepatic lipidosis (HL) in llamas and to evaluate the metabolic changes that develop during feed restriction. 8 healthy adult female llamas. Llamas were fed grass hay at a rate of 0.25% of their body weight per day for 13 to 28 days. Llamas were monitored by use of clinical observation, serum biochemical analyses, and ultrasound-guided liver biopsies. All 8 llamas lost weight and mobilized fat. Five llamas developed HL, including 4 that were nursing crias. During the period of feed restriction, mean serum concentration of bile acids and activities of aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), and gamma-glutamyl transferase (GGT) were significantly higher in llamas that developed HL, compared with llamas that did not. Mean insulin-to-cortisol concentration ratios were lower in llamas with HL before and up to 7 days of feed restriction, compared with those that did not develop HL. HL in llamas may be induced by severe feed restriction, particularly in the face of increased energy demand. Llamas with weight loss attributable to inadequate dietary intake may develop biochemical evidence of hepatopathy and HL. Increases in serum concentration of bile acids and activities of GGT, AST, and SDH may indicate the development of HL in llamas and identify affected animals for aggressive therapeutic intervention.

  9. Induction of hypoxic root metabolism results from physical limitations in O2 bioavailability in microgravity.

    Science.gov (United States)

    Liao, J; Liu, G; Monje, O; Stutte, G W; Porterfield, D M

    2004-01-01

    Numerous spaceflight experiments have noted changes in the roots that are consistent with hypoxia in the root zone. These observations include general ultrastructure analysis and biochemical measurements to direct measurements of stress specific enzymes. In experiments that have monitored alcohol dehydrogenase (ADH), the data shows this hypoxically responsive gene is induced and is associated with increased ADH activity in microgravity. These changes in ADH could be induced either by spaceflight hypoxia resulting from inhibition of gravity mediated O2 transport, or by a non-specific stress response due to inhibition of gravisensing. We tested these hypotheses in a series of two experiments. The objective of the first experiment was to determine if physical changes in gravity-mediated O2 transport can be directly measured, while the second series of experiments tested whether disruption of gravisensing can induce a non-specific ADH response. To directly measure O2 bioavailability as a function of gravity, we designed a sensor that mimics metabolic oxygen consumption in the rhizosphere. Because of these criteria, the sensor is sensitive to any changes in root O2 bioavailability that may occur in microgravity. In a KC-135 experiment, the sensor was implanted in a moist granular clay media and exposed to microgravity during parabolic flight. The resulting data indicated that root O2 bioavailability decreased in phase with gravity. In experiments that tested for non-specific induction of ADH, we compared the response of transgenic Arabidopsis plants (ADH promoted GUS marker gene) exposed to clinostat, control, and waterlogged conditions. The plants were grown on agar slats in a growth chamber before being exposed to the experimental treatments. The plants were stained for GUS activity localization, and subjected to biochemical tests for ADH, and GUS enzyme activity. These tests showed that the waterlogging treatment induced significant increases in GUS and ADH enzyme

  10. Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets

    Directory of Open Access Journals (Sweden)

    Matthew W. McCarthy

    2018-03-01

    Full Text Available Discovering new drugs for treatment of invasive fungal infections is an enduring challenge. There are only three major classes of antifungal agents, and no new class has been introduced into clinical practice in more than a decade. However, recent advances in our understanding of the fungal life cycle, functional genomics, proteomics, and gene mapping have enabled the identification of new drug targets to treat these potentially deadly infections. In this paper, we examine amino acid transport mechanisms and metabolism as potential drug targets to treat invasive fungal infections, including pathogenic yeasts, such as species of Candida and Cryptococcus, as well as molds, such as Aspergillus fumigatus. We also explore the mechanisms by which amino acids may be exploited to identify novel drug targets and review potential hurdles to bringing this approach into clinical practice.

  11. Dietary trans-fatty acids and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Zdzisław Kochan

    2010-12-01

    Full Text Available Trans-fatty acids (TFAs, products of partial hydrogenation of vegetable oils, have become more prevalent in our diet since the 1960s, when they replaced animal fats. TFAs also occur naturally in meat and dairy products from ruminants. There is growing evidence that dietary trans-fatty acids may increase the risk of metabolic syndrome. Several studies have demonstrated adverse effects of TFAs on plasma lipids and lipoproteins. In dietary trials, trans-fatty acids have been shown to raise the total cholesterol/HDL cholesterol ratio and Lp(a levels in blood. Moreover, a high intake of TFAs has been associated with an increased risk of coronary heart disease. Prospective cohort studies have shown that dietary trans-fatty acids promote abdominal obesity and weight gain. In addition, it appears that TFA consumption may be associated with the development of insulin resistance and type 2 diabetes. The documented adverse health effects of TFAs emphasise the importance of efforts to reduce the content of partially hydrogenated vegetable oils in foods.

  12. The initial metabolic conversion of levulinic acid in Cupriavidus necator.

    Science.gov (United States)

    Jaremko, Matt; Yu, Jian

    2011-09-20

    Levulinic acid or 4-ketovaleric acid is a potential renewable substrate for production of polyhydroxyalkanoates. In this work, the initial reactions of LA metabolism by Cupriavidus necator were examined in vitro. The organic acid was converted by membrane-bound crude enzymes obtained from the cells pre-grown on LA, while no LA activity was detected from cells pre-grown on acetic acid. Acetyl-CoA and propionyl-CoA were two major intermediates in the initial reactions of LA conversion. A mass balance on propionyl-CoA accounts for 84 mol% of LA added in vitro. It explains an interesting phenomenon that 3-hydroxbutyrate and 3-hydroxyvalerate are two major monomers of the biopolyester formed from LA, instead of 4-hydroxvalerate that has the similar chemical structure of LA as the precursor. A Monod model was used to describe the kinetics of LA utilization as a sole carbon source or a co-substrate of glucose and fructose. The μ(max) and K(m) of LA alone were 0.26 h⁻¹ and 0.01 g/L, respectively. The content and composition of PHA are also dependent on the culture conditions such as carbon to nitrogen ratio. The in vitro observation is supported by the high utilization rate of LA and the high molar percentage of 3HB and 3HV in the PHA derived from LA. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. The role of bile acids in metabolic regulation.

    Science.gov (United States)

    Vítek, Libor; Haluzík, Martin

    2016-03-01

    Bile acids (BA), long believed to only have lipid-digestive functions, have emerged as novel metabolic modulators. They have important endocrine effects through multiple cytoplasmic as well as nuclear receptors in various organs and tissues. BA affect multiple functions to control energy homeostasis, as well as glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor and the cytoplasmic G protein-coupled BA receptor TGR5 in a variety of tissues. However, BA also are aimed at many other cellular targets in a wide array of organs and cell compartments. Their role in the pathogenesis of diabetes, obesity and other 'diseases of civilization' becomes even more clear. They also interact with the gut microbiome, with important clinical implications, further extending the complexity of their biological functions. Therefore, it is not surprising that BA metabolism is substantially modulated by bariatric surgery, a phenomenon contributing favorably to the therapeutic effects of these surgical procedures. Based on these data, several therapeutic approaches to ameliorate obesity and diabetes have been proposed to affect the cellular targets of BA. © 2016 Society for Endocrinology.

  14. Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction

    NARCIS (Netherlands)

    van Straten, Esther M. E.; Bloks, Vincent W.; van Dijk, Theo H.; Baller, Julius F. W.; Huijkman, Nicolette C. A.; Kuipers, Irma; Verkade, Henkjan J.; Plosch, Torsten

    Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome. Objective: We

  15. 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...

  16. The dehydration stress of couch grass is associated with its lipid metabolism, the induction of transporters and the re-programming of development coordinated by ABA.

    Science.gov (United States)

    Janská, Anna; Svoboda, Pavel; Spiwok, Vojtěch; Kučera, Ladislav; Ovesná, Jaroslava

    2018-05-02

    The wild relatives of crop species represent a potentially valuable source of novel genetic variation, particularly in the context of improving the crop's level of tolerance to abiotic stress. The mechanistic basis of these tolerances remains largely unexplored. Here, the focus was to characterize the transcriptomic response of the nodes (meristematic tissue) of couch grass (a relative of barley) to dehydration stress, and to compare it to that of the barley crown formed by both a drought tolerant and a drought sensitive barley cultivar. Many of the genes up-regulated in the nodes by the stress were homologs of genes known to be mediated by abscisic acid during the response to drought, or were linked to either development or lipid metabolism. Transporters also featured prominently, as did genes acting on root architecture. The resilience of the couch grass node arise from both their capacity to develop an altered, more effective root architecture, but also from their formation of a lipid barrier on their outer surface and their ability to modify both their lipid metabolism and transporter activity when challenged by dehydration stress. Our analysis revealed the nature of dehydration stress response in couch grass. We suggested the tolerance is associated with lipid metabolism, the induction of transporters and the re-programming of development coordinated by ABA. We also proved the applicability of barley microarray for couch grass stress-response analysis.

  17. [Metabolic syndrome reversion by polyunsaturated fatty acids ingestion].

    Science.gov (United States)

    Campos Mondragón, Martha Gabriela; Oliart Ros, Rosa María; Martínez Martinez, Angélica; Méndez Machado, Gustavo Francisco; Angulo Guerrero, Jesús Ofelia

    2013-12-21

    Metabolic syndrome (MS) frequency is growing and diet has an important influence on its evolution. Our objective was to study the effect of 3 sources of polyunsaturated fatty acids on MS parameters in humans. The MS was diagnosed according to the International Diabetes Federation. Three groups of individuals (n=15/group) were quasi-randomly assigned to one of the following treatments during 6 weeks: a) 1.8 g/d n-3 (1.08g eicosapentoaenoic acid+0.72 g docosahexaenoic acid); b) 2.0 g/d conjugated linoleic acid (CLA, 50:50, cis9:trans11, trans10:cis12), and c) 40 g/d walnut. The clinical and biochemical parameters were evaluated at the beginning and the end of the essay. In the group with n-3 the triglycerides level decreased from 183.9 ± 35.2mg/dl to 149.6 ± 29.0mg/dl (P=.007). In the group with walnut the HDL level rose from 41.7 ± 5.2mg/dl to 47.8 ± 5.4 mg/dl (P=.004) and the Castelli index (total cholesterol/HDL) decreased from 4.86 ± 0.97 to 3.82 ± 0.81 (P=.004). There were not significant changes in the CLA group. At the end of the essay, 46.7% of walnut group patients, 46.7% of n-3 group and 20% of CLA group, had no MS. The groups that consumed polyunsaturated fatty acids n-3 and those in walnut in moderate daily doses during 6 weeks had an improvement of the dyslipidemia component of MS, hypertriglyceridemia and low HDL level. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  18. Role of salicylic acid in induction of plant defense system in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    War, Abdul Rashid; Paulraj, Michael Gabriel; War, Mohd Yousf; Ignacimuthu, Savarimuthu

    2011-11-01

    Salicylic acid (SA), a plant hormone plays an important role in induction of plant defense against a variety of biotic and abiotic stresses through morphological, physiological and biochemical mechanisms. A series of experiments were carried out to evaluate the biochemical response of the chickpea (Cicer arietinum L.) plants to a range of SA concentrations (1, 1.5, and 2 mM). Water treated plants were maintained as control. Activities of peroxidase (POD) and polyphenol oxidase (PPO) were evaluated and amounts of total phenols, hydrogen peroxide (H2O2), and proteins were calculated after 96 h of treatment. Plants responded very quickly to SA at 1.5 mM and showed higher induction of POD and PPO activities, besides the higher accumulation of phenols, H2O2 and proteins. Plants treated with SA at 2 mM showed phytotoxic symptoms. These results suggest that SA at 1.5 mM is safe to these plants and could be utilized for the induction of plant defense.

  19. Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

    2017-11-01

    Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( P citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

  20. Induction of Heavy-Metal-Transporting CPX-Type ATPases during Acid Adaptation in Lactobacillus bulgaricus▿

    Science.gov (United States)

    Penaud, S.; Fernandez, A.; Boudebbouze, S.; Ehrlich, S. D.; Maguin, E.; van de Guchte, M.

    2006-01-01

    Lactobacillus bulgaricus is a lactic acid bacteria (LAB) that, through the production of lactic acid, gradually acidifies its environment during growth. In the course of this process, L. bulgaricus acquires an improved tolerance to acidity. A survey of the recently established genome sequence shows that this bacterium possesses few of the pH control functions that have been described in other LAB and raises the question of what other mechanisms could be involved in its adaptation to the decreasing environmental pH. In some bacteria other than LAB, ion transport systems have been implicated in acid adaptation. We therefore studied the expression of this type of transport system during acid adaptation in L. bulgaricus by reverse transcription and real-time quantitative PCR and mapped transcription start sites. Intriguingly, the most significantly induced were three ATPases carrying the CPX signature of heavy-metal transporters. Protein homology and the presence of a conserved sequence motif in the promoter regions of the genes encoding these proteins strongly suggest that they are involved in copper homeostasis. Induction of this system is thought to assist in avoiding indirect damage that could result from medium acidification. PMID:16997986

  1. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

    Science.gov (United States)

    Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

    2013-05-01

    Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

  2. Induction of phytic acid synthesis by abscisic acid in suspension-cultured cells of rice.

    Science.gov (United States)

    Matsuno, Koya; Fujimura, Tatsuhito

    2014-03-01

    A pathway of phytic acid (PA) synthesis in plants has been revealed via investigations of low phytic acid mutants. However, the regulation of this pathway is not well understood because it is difficult to control the environments of cells in the seeds, where PA is mainly synthesized. We modified a rice suspension culture system in order to study the regulation of PA synthesis. Rice cells cultured with abscisic acid (ABA) accumulate PA at higher levels than cells cultured without ABA, and PA accumulation levels increase with ABA concentration. On the other hand, higher concentrations of sucrose or inorganic phosphorus do not affect PA accumulation. Mutations in the genes RINO1, OsMIK, OsIPK1 and OsLPA1 have each been reported to confer low phytic acid phenotypes in seeds. Each of these genes is upregulated in cells cultured with ABA. OsITPK4 and OsITPK6 are upregulated in cells cultured with ABA and in developing seeds. These results suggest that the regulation of PA synthesis is similar between developing seeds and cells in this suspension culture system. This system will be a powerful tool for elucidating the regulation of PA synthesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Electron inductive effects in the radiolysis of substituted phenylboronic acid solutions

    International Nuclear Information System (INIS)

    Brown, B.J.; Fitch, P.G.; Sangster, D.F.

    1976-01-01

    The pulse radiolysis of aqueous solutions of phenylboronic acid PhB(OH) 2 and its m-nitro and m-amino derivatives has been investigated. The transient optical absorption spectra indicate the presence of three intermediate species absorbing with independent maxima at 297, 317 and 400 nm. The 297-nm band has been assigned to the anion formed in an electron capture reaction, i.e. PhB(OH) 2 +epsilonsub(aq) - → PhB(OH) 2 - and the 317-nm band to cyclohexadienyl radicals formed from OH and H attack on OhB(OH) 2 . Hydroxyphenylboronic acid has been identified as the major stable radiation product. For each of the systems studied the respective yield and reactivity of observed intermediate species can be interpreted relative to the inductive effects of substituent groups in agreement with the Hammett relationship. (author)

  4. Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes

    Directory of Open Access Journals (Sweden)

    Cho YY

    2014-11-01

    Full Text Available Yong-Yeon Cho,1 Hyeon-Uk Jeong,1 Jeong-Han Kim,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon, Korea; 2Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea Abstract: Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP, UDP-glucuronosyltransferase (UGT, and sulfotransferase 2A1 (SULT2A1, were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 µM increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5–50 µM did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19 or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1 in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1'-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans. Keywords: honokiol, human hepatocytes, drug interactions, cytochrome P450, UDP-glucuronosyltransferases

  5. Sulfur amino acids metabolism in magnesium deficient rats

    Energy Technology Data Exchange (ETDEWEB)

    Tojo, H.; Kosokawa, Y.; Yamaguchi, K.

    1984-01-01

    Effect of magnesium (Mg) deficiency on sulfur amino acid metabolism was investigated in rats. Young male rats were fed on the diet containing either 2.26 (deficient rats) or 63.18 mg Mg/100g diet (control and low protein rats) for 2 weeks. A remarkable decrease of body weight gain, serum Mg contents and a slight decreases in the hematological parameters such as Hb, Ht and RBC was observed, while the hepatic Mg and Ca was not significantly changed. Erythema and cramps were observed 5 days after feeding on the Mg-depleted diet. The hepatic glutathione and cysteine contents increased in Mg-deficient rats. However, no significant change of cysteine dioxygenase (CDO) activity and taurine content in Mg-deficient rat liver was observed. These results suggest that Mg deficiency affects the utilization and biosynthesis of hepatic glutathione but not the cysteine catabolism.

  6. Protein and amino acid metabolism in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guoyao.

    1989-01-01

    Isolated chick extensor digitorum communis (EDC) muscles and, in some experiments, rat skeletal muscles were used to study a number of aspects of protein and amino acid metabolism. (1) Chick EDC muscles synthesize and release large amounts of alanine and glutamine, which indirectly obtain their amino groups from branched-chain amino acids (BCAA). (2) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) decrease (P < 0.01) alanine synthesis and BCAA transamination in EDC muscles from 24-h fasted chicks by decreasing (P < 0.01) intracellular concentrations of pyruvate due to inhibition of glycolysis. (3) Glutamine is extensively degraded in skeletal muscles from both chicks and rats, thus challenging the traditional view that glutamine oxidation is negligible in skeletal muscle. The cytosolic glutamine aminotransferases L and K in the rat and the mitochondrial phosphate-activated glutaminase in the chick play important roles in the conversion of glutamine to {alpha}-ketoglutarate for further oxidation. (4) Although methionine has been reported to be extensively transaminated in rat skeletal muscle preparations in the absence of other amino acids, transamination of methionine is absent or negligible in chick and rat skeletal muscles in the presence of physiological concentrations of amino acids. (5) Glutamine at 1.0-15 mM increases (P < 0.01) protein synthesis ({sup 3}H-phenylalanine incorporation), and at 10.0-15.0 mM decreases (P < 0.05) protein degradation ({sup 3}H-phenylalanine release from prelabelled protein in vivo) in EDC muscles from fed chicks as compared to muscles incubated in the absence of glutamine. (6) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) has a small but significant inhibitory effect (P < 0.05) on the rate of protein synthesis, but has no effect (P > 0.05) on the rate of protein degradation in EDC muscles from fed chicks.

  7. Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats

    Science.gov (United States)

    2014-01-01

    The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication. PMID:25202970

  8. Dynamics of human whole body amino acid metabolism

    International Nuclear Information System (INIS)

    Young, V.R.

    1981-01-01

    The mechanism of regulation of the nitrogen metabolism in humans under various nutritional and physiological states was examined using stable isotopes. In the simultaneous continuous infusion of 1- [ 13 ] - leucine and α- [ 15 N]- lysine, their fluxed decreased when individuals received lower protein intake. The rates of oxidation and incorporation into body proteins of leucine changed in parallel with the protein intake. Such effects of diet on whole body leucine kinetics were modified by the energy state and dietary energy level. The nitrogen balance was also improved by an excess level of dietary energy. When the intake of dietary protein was lowered below the maintenance level, the whole body flux and de novo synthesis of glycine were lowered, but alanine synthesis was clearly increased. The intravenous infusion of glucose at 4 mg/kg.min, which causes increase in excess blood sugar and plasma insulin, increased the alanine flux, but had no effect on the glycine flux. The rate of albumin synthesis, determined by giving 15 N-glycine orally every 3 hr, decreased with the lowered intake of dietary protein in young men, but not in elderly men. This explains why the serum albumin synthesis increases with the increase in the intake of dietary protein in young men, but not in elderly men. The rate of whole body protein synthesis in young men receiving the L-amino acid diets providing with the required intake of specific amino acid was much lower than that in the men receiving the diets providing with generous intake of specific amino acid. Thus the control mechanism to maintain the homeostasis of body nitrogen and amino acids is related in some unknown way to the nutritional requirement of the hosts. (Kaihara, S.)

  9. Arachidonic acid metabolism in silica-stimulated bovine alveolar macrophages

    International Nuclear Information System (INIS)

    Englen, M.D.

    1989-01-01

    The in vitro production of arachidonic acid (AA) metabolites in adherent bovine alveolar macrophages (BAM) incubated with silica was investigated. BAM were pre-labelled with 3 H-AA, and lipid metabolites released into the culture medium were analyzed by high performance liquid chromatography (HPLC). Lactate dehydrogenase (LDH) release was simultaneously assayed to provide an indication of cell injury. Increasing doses of silica selectively stimulated the 5-lipoxygenase pathway of AA metabolism, while cyclooxygenase metabolite output was suppressed. LDH release increased in a linear, dose-dependent fashion over the range of silica doses used. Moreover, within 15 min following addition of a high silica dose, a shift to the production of 5-lipoxygenase metabolites occurred, accompanied by a reduction in cyclooxygenase products. This rapid alteration in AA metabolism preceded cell injury. To examine the relationship between cytotoxicity and AA metabolite release by BAM exposed to silicas with different cytotoxic and fibrogenic activities, BAM were exposed to different doses of DQ-12, Minusil-5, and Sigma silicas, and carbonyl iron beads. The median effective dose (ED 50 ) of each particulate to stimulate the release of AA metabolites and LDH was calculated. The ED 50 values for DQ-12, Minusil-5, and Sigma silica showed that the relative cytotoxicities of the different silicas for BAM corresponded to the relative potencies of the silicas to elicit 5-lipoxygenase metabolites from BAM. These results indicate that the cytotoxic, and presumed fibrogenic potential, of a silica is correlated with the potency to stimulate the release of leukotrienes from AM

  10. A metabolic pathway for catabolizing levulinic acid in bacteria

    International Nuclear Information System (INIS)

    Rand, Jacqueline M.; Pisithkul, Tippapha; Clark, Ryan L.; Thiede, Joshua M.; Mehrer, Christopher R.

    2017-01-01

    Microorganisms can catabolize a wide range of organic compounds and therefore have the potential to perform many industrially relevant bioconversions. One barrier to realizing the potential of biorefining strategies lies in our incomplete knowledge of metabolic pathways, including those that can be used to assimilate naturally abundant or easily generated feedstocks. For instance, levulinic acid (LA) is a carbon source that is readily obtainable as a dehydration product of lignocellulosic biomass and can serve as the sole carbon source for some bacteria. Yet, the genetics and structure of LA catabolism have remained unknown. Here, we report the identification and characterization of a seven-gene operon that enables LA catabolism in Pseudomonas putida KT2440. When the pathway was reconstituted with purified proteins, we observed the formation of four acyl-CoA intermediates, including a unique 4-phosphovaleryl-CoA and the previously observed 3-hydroxyvaleryl-CoA product. Using adaptive evolution, we obtained a mutant of Escherichia coli LS5218 with functional deletions of fadE and atoC that was capable of robust growth on LA when it expressed the five enzymes from the P. putida operon. Here, this discovery will enable more efficient use of biomass hydrolysates and metabolic engineering to develop bioconversions using LA as a feedstock.

  11. Microbial diversity and metabolic networks in acid mine drainage habitats

    Directory of Open Access Journals (Sweden)

    Celia eMendez-Garcia

    2015-05-01

    Full Text Available Acid mine drainage (AMD emplacements are low-complexity natural systems. Low-pH conditions appear to be the main factor underlying the limited diversity of the microbial populations thriving in these environments, although temperature, ionic composition, total organic carbon and dissolved oxygen are also considered to significantly influence their microbial life. This natural reduction in diversity driven by extreme conditions was reflected in several studies on the microbial populations inhabiting the various micro-environments present in such ecosystems. Early studies based on the physiology of the autochthonous microbiota and the growing success of omics technologies have enabled a better understanding of microbial ecology and function in low-pH mine outflows; however, complementary omics-derived data should be included to completely describe their microbial ecology. Furthermore, recent updates on the distribution of eukaryotes and ultra-micro-archaea demand their inclusion in the microbial characterisation of AMD systems. In this review, we present a complete overview of the bacterial, archaeal (including ultra-micro-archaeal and eukaryotic diversity in these ecosystems and include a thorough depiction of the metabolism and element cycling in AMD habitats. We also review different metabolic network structures at the organismal level, which is necessary to disentangle the role of each member of the AMD communities described thus far.

  12. Dynamic low dose I-123-iodophenylpentadecanoic acid metabolic cardiac imaging

    International Nuclear Information System (INIS)

    Murray, G.L.; Magill, H.L.; Schad, N.C.

    1993-01-01

    Recognition of stunned and hibernating myocardium is essential in this era of cardiac revascularization. Positron emission tomography (PET) accurately identifies viability but is costly and unavailable to most patients. Dynamic low dose I-123-iodophenylpentadecanoic acid (IPPA) metabolic cardiac imaging is a potentially cost-effective alternative to PET. Using transmural myocardial biopsies obtained during coronary bypass surgery as the viability gold standard, resting IPPA imaging agreed with 39/43 (91%) biopsies, with a sensitivity for viability of 33/36(92%) and a specificity of 6/7 (86%) in patients with severe ischemic cardiomyopathy. Eighty percent of IPPA viable, infarcted segments improved wall motion postoperatively. Furthermore, when compared to reinjection thallium (SPECT-Tl) scans after myocardial infarction, there was IPPA-Tl concordance in 27/35 (77%)(Kappa=0.536, p=0.0003). Similar to PET, IPPA demonstrated more viability than SPECT-Tl, 26/35 (74%) vs. 18/35 (51%)(p=0.047). Finally, when compared to transvenous endomyocardial biopsy for detecting rejection following cardiac transplantation, IPPA sensitivity for ≥Grade II rejection was 100%, and IPPA screening assessment for the necessity of biopsy could result in a 31% cost-savings. Therefore, IPPA metabolic cardiac imaging is a safe, inexpensive technique with a promising future. (author)

  13. Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK.

    Science.gov (United States)

    Siddesha, Jalahalli M; Valente, Anthony J; Sakamuri, Siva S V P; Gardner, Jason D; Delafontaine, Patrice; Noda, Makoto; Chandrasekar, Bysani

    2014-07-01

    The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-κB- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H(2)O(2) generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H(2)O(2) generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms. © 2013 Wiley Periodicals, Inc.

  14. The influence of aging on the metabolism of simultaneously administered hexobarbital enantiomers and antipyrine before and after phenobarbital induction in male rats: A longitudinal study

    NARCIS (Netherlands)

    Groen, K.; Breimer, D.D.; Jansen, E.J.; Bezooijen, C.F.A. van

    1994-01-01

    The influence of aging on the metabolism of antipyrine (AP) and hexobarbital enantiomers (R-HB and S-HB) with and without phenobarbital (PB) induction was investigated in a longitudinal study in rats aged 6, 12, 24 and 30 months. The metabolic clearances of AP (Cl(m AP)), R-HB (Cl(m R-HB)) and S-HB

  15. Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor

    Science.gov (United States)

    Hoffart, E; Ghebreghiorghis, L; Nussler, AK; Thasler, WE; Weiss, TS; Schwab, M; Burk, O

    2012-01-01

    BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug-metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two-hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR-regulated genes was measured. Two-hybrid co-activator interaction and co-repressor release assays were utilized to elucidate the molecular mechanism of PXR activation. KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para-hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co-activator recruitment were not observed, para-hydroxy atorvastatin demonstrated only 50% release of co-repressors. CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co-repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR-dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para-hydroxy atorvastatin, might be lower than that of the parent compound. PMID:21913896

  16. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Mei-Fei Yueh

    Full Text Available Triclocarban (3,4,4'-trichlorocarbanilide, TCC is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs. To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR and estrogen receptor alpha (ERα activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR because no induction occurred in hUGT1Car(-/- mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for

  17. Uric acid in metabolic syndrome: From an innocent bystander to a central player

    Science.gov (United States)

    Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.

    2016-01-01

    Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429

  18. Pachymic acid promotes induction of autophagy related to IGF-1 signaling pathway in WI-38 cells.

    Science.gov (United States)

    Lee, Su-Gyeong; Kim, Moon-Moo

    2017-12-01

    The insulin-like growth factor 1 (IGF-1) signaling pathway has spotlighted as a mechanism to elucidate aging associated with autophagy in recent years. Therefore, we have tried to screen an effective compound capable of inducing autophagy to delay aging process. The aim of this study is to investigate whether pachymic acid, a main compound in Poria cocos, induces autophagy in the aged cells. The aging of young cells was induced by treatment with IGF-1 at 50 ng/ml three times every two days. The effect of pachymic acid on cell viability was evaluated in human lung fibroblasts, WI-38 cells, using MTT assay. The induction of autophagy was detected using autophagy detection kit. The expression of proteins related to autophagy and IGF-1 signaling pathway was examined by western blot analysis and immunofluorescence assay. In this study, pachymic acid showed cytotoxic effect in a dose dependent manner and remarkably induced autophagy at the same time. Moreover, pachymic acid increased the expression of proteins related to autophagy such as LC3-II and Beclin1 and decreased the levels of mTor phosphorylation and p70S6K in the aged cells. In particular, pachymic acid increased the expression of p-PI3K, p-FoxO and Catalase. In addition, pachymic acid remarkably increased the expression of IGFBP-3. Above results suggest that pachymic acid could induce autophagy related to IGF-1 signaling pathway in the aged cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Metabolic pathways regulated by abscisic acid, salicylic acid and γ-aminobutyric acid in association with improved drought tolerance in creeping bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2017-01-01

    Abscisic acid (ABA), salicylic acid (SA) and γ-aminobutyric acid (GABA) are known to play roles in regulating plant stress responses. This study was conducted to determine metabolites and associated pathways regulated by ABA, SA and GABA that could contribute to drought tolerance in creeping bentgrass (Agrostis stolonifera). Plants were foliar sprayed with ABA (5 μM), GABA (0.5 mM) and SA (10 μM) or water (untreated control) prior to 25 days drought stress in controlled growth chambers. Application of ABA, GABA or SA had similar positive effects on alleviating drought damages, as manifested by the maintenance of lower electrolyte leakage and greater relative water content in leaves of treated plants relative to the untreated control. Metabolic profiling showed that ABA, GABA and SA induced differential metabolic changes under drought stress. ABA mainly promoted the accumulation of organic acids associated with tricarboxylic acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA strongly stimulated the accumulation of amino acids (proline, serine, threonine and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5-oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids (malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The enhanced drought tolerance could be mainly due to the enhanced respiration metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment (OA) and energy metabolism by SA, and amino acid metabolism related to OA and stress-defense secondary metabolism by GABA. © 2016 Scandinavian Plant Physiology Society.

  20. Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues.

    Science.gov (United States)

    Ralston, Jessica C; Lyons, Claire L; Kennedy, Elaine B; Kirwan, Anna M; Roche, Helen M

    2017-08-21

    Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.

  1. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    Directory of Open Access Journals (Sweden)

    Seher Balaban

    2015-01-01

    Full Text Available Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

  2. Perturbations of Amino Acid Metabolism Associated with Glyphosate-Dependent Inhibition of Shikimic Acid Metabolism Affect Cellular Redox Homeostasis and Alter the Abundance of Proteins Involved in Photosynthesis and Photorespiration1[W][OA

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P.; Bulman, Christopher A.; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H.

    2011-01-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. PMID:21757634

  3. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

    2011-09-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

  4. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Science.gov (United States)

    Norambuena, Fernando; Morais, Sofia; Emery, James A; Turchini, Giovanni M

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

  5. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Directory of Open Access Journals (Sweden)

    Fernando Norambuena

    Full Text Available Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3, with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher

  6. 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...

  7. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

    DEFF Research Database (Denmark)

    Wahlström, Annika; Sayin, Sama I; Marschall, Hanns-Ulrich

    2016-01-01

    The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids......, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host....... Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also...

  8. Cytochrome P-450-catalyzed desaturation of valproic acid in vitro. Species differences, induction effects, and mechanistic studies

    International Nuclear Information System (INIS)

    Rettie, A.E.; Boberg, M.; Rettenmeier, A.W.; Baillie, T.A.

    1988-01-01

    The cytochrome P-450-mediated desaturation of valproic acid (VPA) to its hepatotoxic metabolite, 2-n-propyl-4-pentenoic acid (4-ene-VPA), was examined in liver microsomes from rats, mice, rabbits and humans. The highest substrate turnover was found with microsomes from rabbits (44.2 +/- 2.7 pmol of product/nmol P-450/15 min), while lower activities were observed in preparations from human, mouse, and rat liver, in that order. Pretreatment of animals with phenobarbital led to enhanced rates of formation of 4-ene-VPA in vitro and yielded induction ratios for desaturation ranging from 2.5 to 8.4, depending upon the species. Comparative studies in the rat showed that phenobarbital is a more potent inducer of olefin formation than either phenytoin or carbamazepine. The mechanism of the desaturation reaction was studied by inter- and intramolecular deuterium isotope effect experiments, which demonstrated that removal of a hydrogen atom from the subterminal C-4 position of VPA is rate limiting in the formation of both 4-ene- and 4-hydroxy-VPA. Hydroxylation at the neighboring C-5 position, on the other hand, was highly sensitive to deuterium substitution at that site, but not to deuteration at C-4. Based on these findings, it is proposed that 4-ene- and 4-hydroxy-VPA are products of a common P-450-dependent metabolic pathway, in which a carbon-centered free radical at C-4 serves as the key intermediate. 5-Hydroxy-VPA, in contrast, derives from an independent hydroxylation reaction

  9. Metabolic Effects of a Succinic Acid

    Directory of Open Access Journals (Sweden)

    B. N. Shakh

    2014-01-01

    Full Text Available The paper discusses promises for clinical use of substrate antihypoxants.Objective: to investigate the efficacy of succinate containing  substrate  antihypoxants  on  systemic  oxygen  consumption,  blood  buffer  capacity,  and  changes  in  the  mixed venous blood level of lactate when they are used in gravely sick patients and victims with marked metabolic posthypoxic disorders.Subjects and methods. The trial enrolled 30 patients and victims who had sustained an episode of severe hypoxia of mixed genesis, the severity of which was evaluated by the APACHE II scale and amounted to 23 to 30 scores with a 46 to 70.3% risk of death. The standard infusion program in this group involved the succinate-containing drug 1.5% reamberin solution  in  a  total  dose  of  800  ml.  A  comparison  group  included  15  patients  who  had  undergone  emergency  extensive surgery for abdominal diseases. 400 ml of 10% glucose solution was used as an infusion medium. Oxygen consumption (VO2ml/min and carbon dioxide production (VCO2ml/min were measured before infusion and monitored for 2 hours. Arterial blood gases and acid-base balance (ABB parameters and mixed venous blood lactate levels were examined. Measurements were made before and 30 minutes after the infusion of reamberin or glucose solution.Results. Infusion of 1.5% reamberin solution was followed by a significant increase in minute oxygen consumption from 281.5±21.2 to 310.4±24.4 ml/min. CO2 production declined (on average, from 223.3±6.5 to 206.5±7.59 ml/min. During infusion of 10% glucose solution, all the patients of the comparison group showed a rise in oxygen consumption from 303.6±33.86 to 443.13±32.1 ml/min, i.e. about 1.5-fold. VCO2 changed similarly. The intravenous infusion of 800 ml of 1.5% reamberin solution raised arterial blood buffer capacity, which was reflected by changes in pH, BE, and HCO3. There was a clear trend for lactate values to drop in the

  10. Metabolism and fatty acid profile in fat and lean rainbow trout lines fed with vegetable oil: effect of carbohydrates.

    Directory of Open Access Journals (Sweden)

    Biju Sam Kamalam

    Full Text Available The present study investigated the effect of dietary carbohydrates on metabolism, with special focus on fatty acid bioconversion and flesh lipid composition in two rainbow trout lines divergently selected for muscle lipid content and fed with vegetable oils. These lines were chosen based on previously demonstrated potential differences in LC-PUFA synthesis and carbohydrate utilization. Applying a factorial study design, juvenile trout from the lean (L and the fat (F line were fed vegetable oil based diets with or without gelatinised starch (17.1% for 12 weeks. Blood, liver, muscle, intestine and adipose tissue were sampled after the last meal. Feed intake and growth was higher in the L line than the F line, irrespective of the diet. Moderate postprandial hyperglycemia, strong induction of hepatic glucokinase and repressed glucose-6-phosphatase transcripts confirmed the metabolic response of both lines to carbohydrate intake. Further at the transcriptional level, dietary carbohydrate in the presence of n-3 LC-PUFA deficient vegetable oils enhanced intestinal chylomicron assembly, disturbed hepatic lipid metabolism and importantly elicited a higher response of key desaturase and elongase enzymes in the liver and intestine that endorsed our hypothesis. PPARγ was identified as the factor mediating this dietary regulation of fatty acid bioconversion enzymes in the liver. However, these molecular changes were not sufficient to modify the fatty acid composition of muscle or liver. Concerning the genotype effect, there was no evidence of substantial genotypic difference in lipid metabolism, LC-PUFA synthesis and flesh fatty acid profile when fed with vegetable oils. The minor reduction in plasma glucose and triglyceride levels in the F line was linked to potentially higher glucose and lipid uptake in the muscle. Overall, these data emphasize the importance of dietary macro-nutrient interface in evolving fish nutrition strategies.

  11. Metabolism and fatty acid profile in fat and lean rainbow trout lines fed with vegetable oil: effect of carbohydrates.

    Science.gov (United States)

    Kamalam, Biju Sam; Médale, Françoise; Larroquet, Laurence; Corraze, Geneviève; Panserat, Stephane

    2013-01-01

    The present study investigated the effect of dietary carbohydrates on metabolism, with special focus on fatty acid bioconversion and flesh lipid composition in two rainbow trout lines divergently selected for muscle lipid content and fed with vegetable oils. These lines were chosen based on previously demonstrated potential differences in LC-PUFA synthesis and carbohydrate utilization. Applying a factorial study design, juvenile trout from the lean (L) and the fat (F) line were fed vegetable oil based diets with or without gelatinised starch (17.1%) for 12 weeks. Blood, liver, muscle, intestine and adipose tissue were sampled after the last meal. Feed intake and growth was higher in the L line than the F line, irrespective of the diet. Moderate postprandial hyperglycemia, strong induction of hepatic glucokinase and repressed glucose-6-phosphatase transcripts confirmed the metabolic response of both lines to carbohydrate intake. Further at the transcriptional level, dietary carbohydrate in the presence of n-3 LC-PUFA deficient vegetable oils enhanced intestinal chylomicron assembly, disturbed hepatic lipid metabolism and importantly elicited a higher response of key desaturase and elongase enzymes in the liver and intestine that endorsed our hypothesis. PPARγ was identified as the factor mediating this dietary regulation of fatty acid bioconversion enzymes in the liver. However, these molecular changes were not sufficient to modify the fatty acid composition of muscle or liver. Concerning the genotype effect, there was no evidence of substantial genotypic difference in lipid metabolism, LC-PUFA synthesis and flesh fatty acid profile when fed with vegetable oils. The minor reduction in plasma glucose and triglyceride levels in the F line was linked to potentially higher glucose and lipid uptake in the muscle. Overall, these data emphasize the importance of dietary macro-nutrient interface in evolving fish nutrition strategies.

  12. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  13. Relationship between the murine Ah locus and 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatic metabolism, enzyme induction, and toxicity

    International Nuclear Information System (INIS)

    Shen, E.S.

    1988-01-01

    The influence of the Ah locus and hepatic microsomal enzyme induction on 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) metabolism and hepatotoxicity was investigated using C57BL/6J (C57) and DBA/2J (DBA) mice. C57 mice are more sensitive to toxic and enzyme inductive effects of 2,3,7,8-TCDD than DBA mice. Characterization of interstrain differences in hepatic enzyme induction, 2,3,7,8-TCDD metabolism, and hepatotoxicity may aid in identifying the mechanism(s) of 2,3,7,8-TCDD toxicity. The hepatic uptake and metabolism of [ 14 C]2,3,7,8-TCDD were studied using isolated hepatocytes from control and 2,3,7,8-TCDD-pretreated C57 and DBA mice. Pretreated mice were injected with 2,3,7,8-TCDD at doses that maximally induce aryl hydrocarbon hydroxylase activity or at doses that approach the LD 50 value. Despite the induction of hepatic 7-ethoxyresorufin O-deethylase activity and benzo[a]pyrene metabolism, all 2,3,7,8-TCDD pretreatment doses failed to increase the rate of [ 14 C]2,3,7,8-TCDD metabolism for both C57 and DBA mice. These results suggest that the uptake and rate of hepatic metabolism of 2,3,7,8-TCDD do not correlate with genetic differences at the murine Ah locus

  14. Regulation of glycolysis and level of the Crassulacean acid metabolism.

    Science.gov (United States)

    Pierre, J N; Queiroz, O

    1979-01-01

    Glycolysis shows different patterns of operation and different control steps, depending on whether the level of Crassulacean acid metabolism (CAM) is low or high in the leaves of Kalanchoe blossfeldiana v.Poelln., when subjected to appropriate photoperiodic treatments: at a low level of CAM operation all the enzymes of glycolysis and phosphoenol pyruvate (PEP) carboxylase present a 12 h rhythm of capacity, resulting from the superposition of two 24h rhythms out of phase; phosphofructokinase appears to be the main regulation step; attainment of high CAM level involves (1) an increase in the peak of capacity occurring during the night of all the glycolytic enzymes, thus achieving an over-all 24h rhythm, in strict allometric coherence with the increase in PEP carboxylase capacity, (2) the establishment of different phase relationships between the rhythms of enzyme capacity, and (3) the control of three enzymic steps (phosphofructokinase, the group 3-P-glyceraldehyde dehydrogenase - 3-P-glycerate kinase, and PEP carboxylase). Results show that the hypothesis of allosteric regulation of phosphofructokinase (by PEP) and PEP carboxylase (by malate and glucose-6-P) cannot provide a complete explanation for the temporal organization of glycolysis and that changes in the phase relationships between the rhythms of enzyme capacity along the pathway and a strict correlation between the level of PEP carboxylase capacity and the levels of capacity of the glycolytic enzymes are important components of the regulation of glycolysis in relation to CAM.

  15. Abscisic acid induction of vacuolar H+-ATPase activity in mesembryanthemum crystallinum is developmentally regulated

    Science.gov (United States)

    Barkla; Vera-Estrella; Maldonado-Gama; Pantoja

    1999-07-01

    Abscisic acid (ABA) has been implicated as a key component in water-deficit-induced responses, including those triggered by drought, NaCl, and low- temperature stress. In this study a role for ABA in mediating the NaCl-stress-induced increases in tonoplast H+-translocating ATPase (V-ATPase) and Na+/H+ antiport activity in Mesembryanthemum crystallinum, leading to vacuolar Na+ sequestration, were investigated. NaCl or ABA treatment of adult M. crystallinum plants induced V-ATPase H+ transport activity, and when applied in combination, an additive effect on V-ATPase stimulation was observed. In contrast, treatment of juvenile plants with ABA did not induce V-ATPase activity, whereas NaCl treatment resulted in a similar response to that observed in adult plants. Na+/H+ antiport activity was induced in both juvenile and adult plants by NaCl, but ABA had no effect at either developmental stage. Results indicate that ABA-induced changes in V-ATPase activity are dependent on the plant reaching its adult phase, whereas NaCl-induced increases in V-ATPase and Na+/H+ antiport activity are independent of plant age. This suggests that ABA-induced V-ATPase activity may be linked to the stress-induced, developmentally programmed switch from C3 metabolism to Crassulacean acid metabolism in adult plants, whereas, vacuolar Na+ sequestration, mediated by the V-ATPase and Na+/H+ antiport, is regulated through ABA-independent pathways.

  16. Fatty acid is a potential agent for bone tissue induction: In vitro and in vivo approach.

    Science.gov (United States)

    Cardoso, Guinea Bc; Chacon, Erivelto; Chacon, Priscila Gl; Bordeaux-Rego, Pedro; Duarte, Adriana Ss; Saad, Sara T Olalla; Zavaglia, Cecilia Ac; Cunha, Marcelo R

    2017-12-01

    Our hypothesis was to investigate the fatty acid potential as a bone induction factor. In vitro and in vivo studies were performed to evaluate this approach. Oleic acid was used in a 0.5 wt.% concentration. Polycaprolactone was used as the polymeric matrix by combining solvent-casting and particulate-leaching techniques, with a final porosity of 70 wt.%, investigated by SEM images. Contact angle measurements were produced to investigate the influence of oleic acid on polycaprolactone chains. Cell culture was performed using adipocyte-derived stem cells to evaluate biocompatibility and bioactivity properties. In addition, in vivo studies were performed to evaluate the induction potential of oleic acid addition. Adipocyte-derived stem cells were used to provide differentiation after 21 days of culture. Likewise, information were obtained with in vivo data and cellular invagination was observed on both scaffolds (polycaprolactone and polycaprolactone /oleic acid); interestingly, the scaffold with oleic acid addition demonstrated that cellular migrations are not related to the surrounding tissue, indicating bioactive potential. Our hypothesis is that fatty acid may be used as a potential induction factor for bone tissue engineering. The study's findings indicate oleic acid as a possible agent for bone induction, according to data on cell differentiation, proliferation, and migration. Impact statement The biomaterial combined in this study on bone regeneration is innovative and shows promising results in the treatment of bone lesions. Polycaprolactone (PCL) and oleic acid have been studied separately. In this research, we combined biomaterials to assess the stimulus and the speed of bone healing.

  17. Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

    Science.gov (United States)

    Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G; Cryan, John F; Ross, R Paul; Quigley, Eamonn M; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F; O'Toole, Paul W; Stanton, Catherine

    2012-01-01

    The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (pbreve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (pbreve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (pbreve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (pbreve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (pbreve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.

  18. Hepatic Metabolism of Perfluorinated Carboxylic Acids: A Nuclear Magnetic Resonance Investigation in Vivo

    Science.gov (United States)

    1995-01-17

    Reo, C. M. Goecke, L. Narayanan, and B. M. Jarnot. "Effects of Perfluoro-n- octanoic Acid , Perfluoro-n-decanoic Acid , and Clofibrate on Hepatic...SUBTITLE 7C 5. FUNDING NUMBERS" Hepatic Metabolism of Perfluorinated Carboxylic Acids : A Nuclear Magnetic Resonance Investigation in Vivo G-AFOSR-90-0148 6...octanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA). These Air Force chemicals belong to a class of CU’. compounds known as peroxisome

  19. Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis.

    Science.gov (United States)

    Roda, A; Aldini, R; Camborata, C; Spinozzi, S; Franco, P; Cont, M; D'Errico, A; Vasuri, F; Degiovanni, A; Maroni, L; Adorini, L

    2017-07-01

    Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride-induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal clearance were lower than in controls. BAs' qualitative and quantitative compositions were not modified by a single administration of OCA. In all the matrices studied, OCA concentrations were significantly lower than those of endogenous BAs, potentially much more cytotoxic. © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  20. FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways.

    Directory of Open Access Journals (Sweden)

    Ai-Luen Wu

    Full Text Available Fibroblast growth factor 19 (FGF19 is a hormone-like protein that regulates carbohydrate, lipid and bile acid metabolism. At supra-physiological doses, FGF19 also increases hepatocyte proliferation and induces hepatocellular carcinogenesis in mice. Much of FGF19 activity is attributed to the activation of the liver enriched FGF Receptor 4 (FGFR4, although FGF19 can activate other FGFRs in vitro in the presence of the coreceptor βKlotho (KLB. In this report, we investigate the role of FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation.

  1. Nickel Deficiency Disrupts Metabolism of Ureides, Amino Acids, and Organic Acids of Young Pecan Foliage[OA

    Science.gov (United States)

    Bai, Cheng; Reilly, Charles C.; Wood, Bruce W.

    2006-01-01

    The existence of nickel (Ni) deficiency is becoming increasingly apparent in crops, especially for ureide-transporting woody perennials, but its physiological role is poorly understood. We evaluated the concentrations of ureides, amino acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni-S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch). Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but total ureides, urea concentration, and urease activity were reduced. Disruption of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine, valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids, and lower concentrations of histidine and glutamic acid. Ni deficiency also disrupted the citric acid cycle, the second stage of respiration, where Ni-D foliage contained very low levels of citrate compared to Ni-S foliage. Disruption of carbon metabolism was also via accumulation of lactic and oxalic acids. The results indicate that mouse-ear, a key morphological symptom, is likely linked to the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and margins of leaflets. Our results support the role of Ni as an essential plant nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan is evidence of the existence of unidentified physiological roles for Ni in pecan. PMID:16415214

  2. Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

    Directory of Open Access Journals (Sweden)

    Lucio Della Guardia

    2018-05-01

    Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

  3. Progress of succinic acid production from renewable resources: Metabolic and fermentative strategies.

    Science.gov (United States)

    Jiang, Min; Ma, Jiangfeng; Wu, Mingke; Liu, Rongming; Liang, Liya; Xin, Fengxue; Zhang, Wenming; Jia, Honghua; Dong, Weiliang

    2017-12-01

    Succinic acid is a four-carbon dicarboxylic acid, which has attracted much interest due to its abroad usage as a precursor of many industrially important chemicals in the food, chemicals, and pharmaceutical industries. Facing the shortage of crude oil supply and demand of sustainable development, biological production of succinic acid from renewable resources has become a topic of worldwide interest. In recent decades, robust producing strain selection, metabolic engineering of model strains, and process optimization for succinic acid production have been developed. This review provides an overview of succinic acid producers and cultivation technology, highlight some of the successful metabolic engineering approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Possible role of jasmonic acid in the regulation of floral induction, evocation and floral differentiation in Lemna minor L.

    Science.gov (United States)

    Krajncic, B; Kristl, J; Janzekovic, I

    2006-01-01

    Jasmonic acid (JA) is implicated in a wide variety of developmental and physiological processes in plants. Here, we studied the effects of JA and the combination of JA and ethylenediamine-dio-hydroxyphenyl-acetic acid (EDDHA) on flowering in Lemna minor in axenical cultures. JA (0.475-47.5 nmol l(-1)) enhanced floral induction in L. minor under long-day (LD) conditions. Under the same conditions, at a concentration of 237.5 nmol l(-1), JA inhibited floral induction, and at a concentration of 475 nmol l(-1) it prevented floral induction. Under LD conditions with LD preculture, a combination of EDDHA (20,500 nmol l(-1)) and JA (47.5 nmol l(-1)) had a synergistic effect on the promotion of floral induction. Floral induction was enhanced to the greatest extent in experiments with LD precultures. Microscopic examination of microphotographs of histological sections showed that JA and, to an even greater extent, JA+EDDHA at optimal concentrations promote apical floral induction (evocation). Furthermore, JA, and to an even greater extent JA in combination with EDDHA in an optimal concentration, also promote flower differentiation, especially the development of stamens, as is evident from the microphotographs. The experimental results show that JA promotes floral induction in other species of Lemnaceae from various groups according to their photoperiodic response. The results support our hypothesis that, in addition to previously ascribed functions, JA may regulate floral induction, evocation and floral differentiation. Our hypothesis is supported also by the results obtained by quantitative determination of endogenous JA levels in L. minor at three growth stages. The levels of endogenous JA decreased from 389 ng JA g(-1) (fresh weight) of L. minor during the vegetative stage to 217 ng JA g(-1) during the evocation stage, and to 37.5 ng JA g(-1) during the flowering stage, which proves that JA is used for flowering.

  5. Uric Acid, Metabolic Syndrome and Atherosclerosis: The Chicken or the Egg, Which Comes First?

    Science.gov (United States)

    De Pergola, Giovanni; Cortese, Francesca; Termine, Gaetano; Meliota, Giovanni; Carbonara, Rossella; Masiello, Michele; Cortese, Anna M; Silvestris, Francesco; Caccavo, Domenico; Ciccone, Marco Matteo

    2018-01-01

    A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease. The study aimed to determine the relationship among serum uric acid and metabolic syndrome and atherosclerosis, by means of carotid intima media-thickness, in a cohort of 811 otherwise healthy overweight/obese subjects, without overt atherosclerosis not using any kind of drug. Uric acid levels were positively related to male gender, waist circumference, BMI, systolic and diastolic pressure levels, fasting insulin, fasting glucose, HOMA-IR, triglycerides, total cholesterol, LDL cholesterol, the presence of metabolic syndrome and the number of the components of metabolic syndrome and negatively related to HDL cholesterol levels. No correlation was found between uric acid and carotid intima media thickness. At the multiple regression analysis, only waist circumference and triglycerides (positively) and HDL-cholesterol (negatively) maintained an independent association with uric acid as dependent variable, while age, female gender and uric acid showed a significant independent association with metabolic syndrome as dependent variable. Moreover, the analysis of the odd ratios showed that the risk of developing metabolic syndrome was consistent with uric acid levels ranging from 3 mg/dl to 8 mg/dl. The presence of metabolic syndrome does not seem to provide hyperuricemia. By contrast, higher serum uric acid level may predict the risk of metabolic syndrome. Moreover, our results suggest that uric acid cannot be considered a risk factor for early atherosclerosis, at least when assessed using carotid ultrasound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Induction of salicylic acid-mediated defense response in perennial ryegrass against infection by Magnaporthe oryzae.

    Science.gov (United States)

    Rahman, Alamgir; Kuldau, Gretchen A; Uddin, Wakar

    2014-06-01

    Incorporation of plant defense activators is an innovative approach to development of an integrated strategy for the management of turfgrass diseases. The effects of salicylic acid (SA), benzothiadiazole (BTH, chemical analog of SA), jasmonic acid (JA), and ethephon (ET, an ethylene-releasing compound) on development of gray leaf spot in perennial ryegrass (Lolium perenne L.) caused by Magnaporthe oryzae were evaluated. Gray leaf spot disease incidence and severity were significantly decreased when plants were treated prior to inoculation with SA, BTH, and partially by ET but not by JA. Accumulation of endogenous SA and elevated expression of pathogenesis-related (PR)-1, PR-3.1, and PR-5 genes were associated with inoculation of plants by M. oryzae. Treatment of plants with SA enhanced expression levels of PR-3.1 and PR-5 but did not affect the PR-1 level, whereas BTH treatment enhanced relative expression levels of all three PR genes. Microscopic observations of leaves inoculated with M. oryzae revealed higher frequencies of callose deposition at the penetration sites in SA- and BTH-treated plants compared with the control plants (treated with water). These results suggest that early and higher induction of these genes by systemic resistance inducers may provide perennial ryegrass with a substantial advantage to defend against infection by M. oryzae.

  7. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Vaughan Roger A

    2012-10-01

    Full Text Available Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was quantified by measuring extracellular acidification and oxygen consumption rates. Results Omega 3 significantly induced metabolic genes as well as oxidative metabolism (oxygen consumption, glycolytic capacity (extracellular acidification, and metabolic rate compared with control. Both treatments significantly increased mitochondrial content. Conclusion Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control.

  8. Impact of metabolism and growth phase on the hydrogen isotopic composition of microbial fatty acids

    Science.gov (United States)

    Heinzelmann, Sandra M.; Villanueva, Laura; Sinke-Schoen, Danielle; Sinninghe Damsté, Jaap S.; Schouten, Stefan; van der Meer, Marcel T. J.

    2015-01-01

    Microorganisms are involved in all elemental cycles and therefore it is important to study their metabolism in the natural environment. A recent technique to investigate this is the hydrogen isotopic composition of microbial fatty acids, i.e., heterotrophic microorganisms produce fatty acids enriched in deuterium (D) while photoautotrophic and chemoautotrophic microorganisms produce fatty acids depleted in D compared to the water in the culture medium (growth water). However, the impact of factors other than metabolism have not been investigated. Here, we evaluate the impact of growth phase compared to metabolism on the hydrogen isotopic composition of fatty acids of different environmentally relevant microorganisms with heterotrophic, photoautotrophic and chemoautotrophic metabolisms. Fatty acids produced by heterotrophs are enriched in D compared to growth water with εlipid/water between 82 and 359‰ when grown on glucose or acetate, respectively. Photoautotrophs (εlipid/water between −149 and −264‰) and chemoautotrophs (εlipid/water between −217 and −275‰) produce fatty acids depleted in D. Fatty acids become, in general, enriched by between 4 and 46‰ with growth phase which is minor compared to the influence of metabolisms. Therefore, the D/H ratio of fatty acids is a promising tool to investigate community metabolisms in nature. PMID:26005437

  9. A Comparative Study of the Radical-scavenging Activity of the Phenolcarboxylic Acids Caffeic Acid, p-Coumaric Acid, Chlorogenic Acid and Ferulic Acid, With or Without 2-Mercaptoethanol, a Thiol, Using the Induction Period Method

    Directory of Open Access Journals (Sweden)

    Seiichiro Fujisawa

    2008-10-01

    Full Text Available Phenolcarboxylic acid antioxidants do not act in vivo as radical-scavengers in isolation, but rather together with GSH (glutathione, a coantioxidant, they constitute an intricate antioxidant network. Caffeic acid, p-coumaric acid, ferulic acid and chlorogenic acid with or without 2-mercaptoethanol (ME, as a substitute for GSH, was investigated by the induction period (IP method for polymerization of methyl methacrylate (MMA initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN, a source of alkyl radicals, R. and benzoyl peroxide (BPO, a source of peroxy radicals, PhCOO. using differential scanning calorimetry (DSC. Upon PhCOO. radical scavenging, the stoichiometric factors (n, number of free radical trapped by one mole of antioxidant for caffeic acid, ferulic acid, p-coumaric acid and chlorogenic acid were 2.4, 1.8, 1.7 and 0.9, whereas upon R. radical scavenging, the corresponding values were 1.3, 1.2, 1.0 and 0.8, respectively. Antioxidants with n values close to 2 suggest the stepwise formation of semiquinone radicals and quinones. By contrast, those with n values close to 1 suggest the formation of dimers after single-electron oxidation, possibly due to recombination of corresponding aryloxy radicals. The ratio of the rate constant of inhibition to that of propagation (kinh/kp declined in the order chlorogenic acid > p-coumaric acid > ferulic acid > caffeic acid. The ratio of the observed IP for the phenolcarboxylic acid/2-mercapto-ethanol (ME mixture (1:1 molar ratio (A to the calculated IP (the simple sum of phenol acid antioxidant and ME (B was investigated. Upon R. scavenging, the caffeic acid or p-coumaric acid/ME mixture was A/B > 1, particularly the former was 1.2, suggesting a synergic effect. By contrast, upon PhCOO. scavenging, the corresponding mixture was A/B < 1, particularly the latter was 0.7, suggesting an antagonistic effect. Upon both radicals scavenging, the A/B for the ferulic acid or chlorogenic acid

  10. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Hornstra, G.; Koning, T.J.; Smeitink, J.A.M.; Bakker, H.D.; Klerk, H. de; Rubio-Gozalbo, M.E.

    2006-01-01

    Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because

  11. Effect of Toxicants on Fatty Acid Metabolism in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    David Grünig

    2018-04-01

    Full Text Available Impairment of hepatic fatty acid metabolism can lead to liver steatosis and injury. Testing drugs for interference with hepatic fatty acid metabolism is therefore important. To find out whether HepG2 cells are suitable for this purpose, we investigated the effect of three established fatty acid metabolism inhibitors and of three test compounds on triglyceride accumulation, palmitate metabolism, the acylcarnitine pool and dicarboxylic acid accumulation in the cell supernatant and on ApoB-100 excretion in HepG2 cells. The three established inhibitors [etomoxir, methylenecyclopropylacetic acid (MCPA, and 4-bromocrotonic acid (4-BCA] depleted mitochondrial ATP at lower concentrations than cytotoxicity occurred, suggesting mitochondrial toxicity. They inhibited palmitate metabolism at similar or lower concentrations than ATP depletion, and 4-BCA was associated with cellular fat accumulation. They caused specific changes in the acylcarnitine pattern and etomoxir an increase of thapsic (C18 dicarboxylic acid in the cell supernatant, and did not interfere with ApoB-100 excretion (marker of VLDL export. The three test compounds (amiodarone, tamoxifen, and the cannabinoid WIN 55,212-2 depleted the cellular ATP content at lower concentrations than cytotoxicity occurred. They all caused cellular fat accumulation and inhibited palmitate metabolism at similar or higher concentrations than ATP depletion. They suppressed medium-chain acylcarnitines in the cell supernatant and amiodarone and tamoxifen impaired thapsic acid production. Tamoxifen and WIN 55,212-2 decreased cellular ApoB-100 excretion. In conclusion, the established inhibitors of fatty acid metabolism caused the expected effects in HepG2 cells. HepG cells proved to be useful for the detection of drug-associated toxicities on hepatocellular fatty acid metabolism.

  12. 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.

  13. Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids.

    Science.gov (United States)

    Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D

    2016-04-01

    In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short

  14. Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites

    Science.gov (United States)

    Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi

    2011-01-01

    Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a “one pot” suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using 13C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems. PMID:21825143

  15. The influence of lactate and dipyridamole on myocardial fatty acid metabolism in man, traced with 123I-17-iodoheptadecanoic acid

    International Nuclear Information System (INIS)

    Duwel, C.M.B.; Visser, F.C.; Eenige, M.J. van; Roos, J.P.; Westera, G.

    1990-01-01

    Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123 I-17-iodoheptadecanoic acid ( 123 I-17-HDA). In patients (paired, n=7) lactate loading decreased the uptake of 123 I-17-HDA significantly from 27 (control:22-36) to 20 counts/min/pixel (16-31; p 123 I-17-HDA scintigraphy of the heart. (orig.) [de

  16. 13C Metabolic Flux Analysis for systematic metabolic engineering of S. cerevisiae for overproduction of fatty acids.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    2016-10-01

    Full Text Available Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here we used flux-based modeling approaches to improve yields of fatty acids in S. cerevisiae. We combined 13C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from Y. lipolytica as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for down-regulation in terms of acetyl-CoA consumption. These genetic modifications were applied to S. cerevisiae WRY2, a strain that is capable of producing 460 mg L of free fatty acids. With the addition of ATP citrate lyase and down-regulation of malate synthase the engineered strain produced 26 per cent more free fatty acids. Further increases in free fatty acid production of 33 per cent were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by 70 per cent.

  17. Effects of Butter and Phytanic acid intake on metabolic parameters and T-cell polarization

    DEFF Research Database (Denmark)

    Drachmann, Tue

    The still growing obesity epidemic is a major risk for our society, as it is associated with the development of the so called metabolic syndrome, which is a clinical diagnosis correlated to development of metabolic disorders. Lack of physical activity, excess energy intake, and nutritional factors...... addition of phytanic acid. Third, we investigated butter and phytanic acid effects on human T-cell polarization, both by in vitro incubation with phytanic acid, and by a 12 weeks intervention with intake of butter. Finally, we performed two human interventions, first one with intake of butter and cheese...... fatty acids are raised in dairy fat along with the amount of green plant material intake of the cattle. Phytanic acid is one of these minor fatty acids, due to agonist activities for nuclear receptors with central roles in among others the lipid and glucose metabolism. To determine the effects of both...

  18. Fatty Acids Consumption: The Role Metabolic Aspects Involved in Obesity and Its Associated Disorders

    Directory of Open Access Journals (Sweden)

    Priscila Silva Figueiredo

    2017-10-01

    Full Text Available Obesity and its associated disorders, such as insulin resistance, dyslipidemia, metabolic inflammation, dysbiosis, and non-alcoholic hepatic steatosis, are involved in several molecular and inflammatory mechanisms that alter the metabolism. Food habit changes, such as the quality of fatty acids in the diet, are proposed to treat and prevent these disorders. Some studies demonstrated that saturated fatty acids (SFA are considered detrimental for treating these disorders. A high fat diet rich in palmitic acid, a SFA, is associated with lower insulin sensitivity and it may also increase atherosclerosis parameters. On the other hand, a high intake of eicosapentaenoic (EPA and docosahexaenoic (DHA fatty acids may promote positive effects, especially on triglyceride levels and increased high-density lipoprotein (HDL levels. Moreover, polyunsaturated fatty acids (PUFAs and monounsaturated fatty acids (MUFAs are effective at limiting the hepatic steatosis process through a series of biochemical events, such as reducing the markers of non-alcoholic hepatic steatosis, increasing the gene expression of lipid metabolism, decreasing lipogenic activity, and releasing adiponectin. This current review shows that the consumption of unsaturated fatty acids, MUFA, and PUFA, and especially EPA and DHA, which can be applied as food supplements, may promote effects on glucose and lipid metabolism, as well as on metabolic inflammation, gut microbiota, and hepatic metabolism.

  19. Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

    Science.gov (United States)

    Chen, Rui; Han, Su; Liu, Xuefeng; Wang, Kunpeng; Zhou, Yong; Yang, Chundong; Zhang, Xi

    2018-05-15

    Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. [Percentage of uric acid calculus and its metabolic character in Dongjiang River valley].

    Science.gov (United States)

    Chong, Hong-Heng; An, Geng

    2009-02-15

    To study the percentage of uric acid calculus in uroliths and its metabolic character in Dongjiang River valley. To analyze the chemical composition of 290 urinary stones by infrared (IR) spectroscopy and study the ratio changes of uric acid calculus. Uric acid calculus patients and healthy people were studied. Personal characteristics, dietary habits were collected. Conditional logistic regression was used for data analysis and studied the dietary risk factors of uric acid calculus. Patients with uric acid calculus, calcium oxalate and those without urinary calculus were undergone metabolic evaluation analysis. The results of uric acid calculus patients compared to another two groups to analysis the relations between the formation of uric acid calculus and metabolism factors. Uric acid calculi were found in 53 cases (18.3%). The multiple logistic regression analysis suggested that low daily water intake, eating more salted and animal food, less vegetable were very closely associated with uric acid calculus. Comparing to calcium oxalate patients, the urine volume, the value of pH, urine calcium, urine oxalic acid were lower, but uric acid was higher than it. The value of pH, urine oxalic acid and citric acid were lower than them, but uric acid and urine calcium were higher than none urinary calculus peoples. Blood potassium and magnesium were lower than them. The percentage of uric acid stones had obvious advanced. Less daily water intake, eating salted food, eating more animal food, less vegetables and daily orange juice intake, eating sea food are the mainly dietary risk factors to the formation of uric acid calculus. Urine volume, the value of pH, citric acid, urine calcium, urine uric acid and the blood natrium, potassium, magnesium, calcium, uric acid have significant influence to the information of uric acid stones.

  1. 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

  2. Abscisic Acid Induction of Vacuolar H+-ATPase Activity in Mesembryanthemum crystallinum Is Developmentally Regulated1

    Science.gov (United States)

    Barkla, Bronwyn J.; Vera-Estrella, Rosario; Maldonado-Gama, Minerva; Pantoja, Omar

    1999-01-01

    Abscisic acid (ABA) has been implicated as a key component in water-deficit-induced responses, including those triggered by drought, NaCl, and low- temperature stress. In this study a role for ABA in mediating the NaCl-stress-induced increases in tonoplast H+-translocating ATPase (V-ATPase) and Na+/H+ antiport activity in Mesembryanthemum crystallinum, leading to vacuolar Na+ sequestration, were investigated. NaCl or ABA treatment of adult M. crystallinum plants induced V-ATPase H+ transport activity, and when applied in combination, an additive effect on V-ATPase stimulation was observed. In contrast, treatment of juvenile plants with ABA did not induce V-ATPase activity, whereas NaCl treatment resulted in a similar response to that observed in adult plants. Na+/H+ antiport activity was induced in both juvenile and adult plants by NaCl, but ABA had no effect at either developmental stage. Results indicate that ABA-induced changes in V-ATPase activity are dependent on the plant reaching its adult phase, whereas NaCl-induced increases in V-ATPase and Na+/H+ antiport activity are independent of plant age. This suggests that ABA-induced V-ATPase activity may be linked to the stress-induced, developmentally programmed switch from C3 metabolism to Crassulacean acid metabolism in adult plants, whereas, vacuolar Na+ sequestration, mediated by the V-ATPase and Na+/H+ antiport, is regulated through ABA-independent pathways. PMID:10398716

  3. Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Broström, Julia M. [Division of Occupational and Environmental Medicine, Lund University, SE 221 85 Lund (Sweden); Ye, Zhi-wei [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm (Sweden); Axmon, Anna; Littorin, Margareta; Tinnerberg, Håkan; Lindh, Christian H. [Division of Occupational and Environmental Medicine, Lund University, SE 221 85 Lund (Sweden); Zheng, Huiyuan; Ghalali, Aram; Stenius, Ulla [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm (Sweden); Jönsson, Bo A.G. [Division of Occupational and Environmental Medicine, Lund University, SE 221 85 Lund (Sweden); Högberg, Johan, E-mail: johan.hogberg@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm (Sweden)

    2015-09-15

    Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to < 5 ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10 min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose–response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting “sneezing”, the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity. - Highlights: • Human epithelial cells release autotaxin in response to 1 nM toluene diisocyanate (TDI). • The release involves P2X4 and P2X7 receptors and is modulated by ATP and MCP-1. • Lysophosphatidic acid (LPA) was measured in workers exposed to < 5 ppb TDI. • LPA in plasma correlated to TDI exposure

  4. Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production.

    Directory of Open Access Journals (Sweden)

    Caroline Colijn

    2009-08-01

    Full Text Available Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression, extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB. Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data.

  5. 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.

  6. Metabolic engineering of Ustilago trichophora TZ1 for improved malic acid production

    Directory of Open Access Journals (Sweden)

    Thiemo Zambanini

    2017-06-01

    These results open up a wide range of possibilities for further optimization, especially combinatorial metabolic engineering to increase the flux from pyruvate to malic acid and to reduce by-product formation.

  7. How to Do It. Plant Eco-Physiology: Experiments on Crassulacean Acid Metabolism, Using Minimal Equipment.

    Science.gov (United States)

    Friend, Douglas J. C.

    1990-01-01

    Features of Crassulacean Acid Metabolism plants are presented. Investigations of a complex eco-physiological plant adaptation to the problems of growth in an arid environment are discussed. Materials and procedures for these investigations are described. (CW)

  8. Gut microbiota and nuclear receptors in bile acid and lipid metabolism : bile acids, more than soaps

    NARCIS (Netherlands)

    Out, Carolien

    2014-01-01

    Metabolic syndrome refers to the combination of obesity, hypertension, dyslipidemia and insulin resistance. Metabolic syndrome increases the chance on cardiovascular disease and type 2 diabetes. Strategies to prevent and treat these metabolic derangements are therefore urgently needed. For this

  9. Docosahexaenoic acid levels in blood and metabolic syndrome in obese children: is there a link?

    OpenAIRE

    Lassandro, C.; Banderali, G.; Radaelli, G.; Borghi, E.; Moretti, F.; Verduci, E.

    2015-01-01

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DH...

  10. Systems metabolic engineering design: fatty acid production as an emerging case study.

    Science.gov (United States)

    Tee, Ting Wei; Chowdhury, Anupam; Maranas, Costas D; Shanks, Jacqueline V

    2014-05-01

    Increasing demand for petroleum has stimulated industry to develop sustainable production of chemicals and biofuels using microbial cell factories. Fatty acids of chain lengths from C6 to C16 are propitious intermediates for the catalytic synthesis of industrial chemicals and diesel-like biofuels. The abundance of genetic information available for Escherichia coli and specifically, fatty acid metabolism in E. coli, supports this bacterium as a promising host for engineering a biocatalyst for the microbial production of fatty acids. Recent successes rooted in different features of systems metabolic engineering in the strain design of high-yielding medium chain fatty acid producing E. coli strains provide an emerging case study of design methods for effective strain design. Classical metabolic engineering and synthetic biology approaches enabled different and distinct design paths towards a high-yielding strain. Here we highlight a rational strain design process in systems biology, an integrated computational and experimental approach for carboxylic acid production, as an alternative method. Additional challenges inherent in achieving an optimal strain for commercialization of medium chain-length fatty acids will likely require a collection of strategies from systems metabolic engineering. Not only will the continued advancement in systems metabolic engineering result in these highly productive strains more quickly, this knowledge will extend more rapidly the carboxylic acid platform to the microbial production of carboxylic acids with alternate chain-lengths and functionalities. © 2014 Wiley Periodicals, Inc.

  11. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    Xiaoxia Gao

    2018-01-01

    Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

  12. Mechanism of long chain monoenoic fatty acids acting on the energy metabolism of heart

    Energy Technology Data Exchange (ETDEWEB)

    Buddecke, E; Filipovic, I; Wortberg, B; Seher, A

    1975-01-01

    The oxidation of 1-/sup 14/C-erucic (Csub(22:1)) and 1-/sup 14/C-nervonic (Csub(24:1)) acid was studied compared to 1-/sup 14/C-palmitic and -oleic acid in isolated rat and pig heart mitochondria. After mitochondrial incubation with the albumin-bound fatty acids only small amounts of /sup 14/CO/sub 2/ developed from the oxidation of the long chain monoenoic acids as compared to palmitic or oleic acid. The slow down of the oxidation rate was more pronounced in rat than in pig heart mitochondria. The oxidation of palmitic or oleic acid was not found to be inhibited by the C/sub 20/-C/sub 24/-monoeneic acids, whereas palmitic or oleic acid inhibited the oxidation of erucic acid competitively. From present findings an idea may be developed of the interference on fatty acid metabolism in heart muscle by erucic and other long chain monenoic acids.

  13. Systems biology and metabolic engineering of lactic acid bacteria for improved fermented foods

    NARCIS (Netherlands)

    Flahaut, N.A.L.; Vos, de W.M.

    2014-01-01

    Lactic acid bacteria have long been used in industrial dairy and other food fermentations that make use of their metabolic activities leading to products with specific organoleptic properties. Metabolic engineering is a rational approach to steer fermentations toward the production of desired

  14. CPT1A Missense Mutation Associated with Fatty Acid Metabolism and Reduced Height in Greenlanders

    DEFF Research Database (Denmark)

    Skotte, Line; Koch, Anders; Yakimov, Victor

    2017-01-01

    Background - Inuit have lived for thousands of years in an extremely cold environment on a diet dominated by marine-derived fat. To investigate how this selective pressure has affected the genetic regulation of fatty acid metabolism, we assessed 233 serum metabolic phenotypes in a population-base...

  15. Alternative carbohydrate reserves used in the daily cycle of crassulacean acid metabolism

    Science.gov (United States)

    C.C. Black; J.-Q. Chen; R.L. Doong; M.N. Angelov; Shi-Jean S. Sung

    1996-01-01

    Each day a massive interlocked biochemical cycle occurs in the green tissues of crassulacean acid metabolism plants.The function of this interlocked cycle, in its simplest context, is to furnish most of the CO2 for CAM plant photosynthesis.In this unified presentation our aims are (1) to divide CAM plants into two metabolic groups, (2) to...

  16. The role of energy & fatty acid metabolism in obesity and insulin resistance

    NARCIS (Netherlands)

    Heemskerk, Mattijs Maria

    2015-01-01

    In today’s world, more people die from complications of overweight than from underweight. But not all individuals are equally prone to develop metabolic complications, such as obesity and insulin resistance. This thesis focuses on the differences in the energy and fatty acid metabolism that play a

  17. Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome

    NARCIS (Netherlands)

    Krzystek-Korpacka, Malgorzata; Patryn, Eliza; Bednarz-Misa, Iwona; Mierzchala, Magdalena; Hotowy, Katarzyna; Czapinska, Elzbieta; Kustrzeba-Wojcicka, Irena; Gamian, Andrzej; Noczynska, Anna

    2011-01-01

    Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters

  18. Metabolism of 2-deoxyglyconic acid in plants and bakers yeast

    International Nuclear Information System (INIS)

    Gakhokidze, R.A.; Beriashvili, L.T.; Chigvinadze, T.D.

    1996-01-01

    During photosynthesis in Phaseolus vulgaris haricot bean and Zea mays leaves, assimilated carbon 14 CO 2 is rapidly incorporated into aldonic acids including 2-deoxygluconic acid whose radioactivity was relatively high. In these plants, radioactive carbon of 2-deoxy-D-gluconic acid prepared from 1-6 14 C-D-glucose is actively involved in the formation of sugars, organic acids, and amino acids. In baking yeast Saccharomyces cerevisiae, the rate of respiration-dependent oxidation of 2-deoxy-D-gluconic acid differs versus the rate of D-glucose oxidation [ru

  19. Systems Analysis of Lactose Metabolism in Trichoderma reesei Identifies a Lactose Permease That Is Essential for Cellulase Induction

    Science.gov (United States)

    Ivanova, Christa; Bååth, Jenny A.; Seiboth, Bernhard; Kubicek, Christian P.

    2013-01-01

    Trichoderma reesei colonizes predecayed wood in nature and metabolizes cellulose and hemicellulose from the plant biomass. The respective enzymes are industrially produced for application in the biofuel and biorefinery industry. However, these enzymes are also induced in the presence of lactose (1,4-0-ß-d-galactopyranosyl-d-glucose), a waste product from cheese manufacture or whey processing industries. In fact, lactose is the only soluble carbon source that induces these enzymes in T. reesei on an industrial level but the reason for this unique phenomenon is not understood. To answer this question, we used systems analysis of the T. reesei transcriptome during utilization of lactose. We found that the respective CAZome encoded all glycosyl hydrolases necessary for cellulose degradation and particularly for the attack of monocotyledon xyloglucan, from which ß-galactosides could be released that may act as the inducers of T. reesei’s cellulases and hemicellulases. In addition, lactose also induces a high number of putative transporters of the major facilitator superfamily. Deletion of fourteen of them identified one gene that is essential for lactose utilization and lactose uptake, and for cellulase induction by lactose (but not sophorose) in pregrown mycelia of T. reesei. These data shed new light on the mechanism by which T. reesei metabolizes lactose and offers strategies for its improvement. They also illuminate the key role of ß-D-galactosides in habitat specificity of this fungus. PMID:23690947

  20. Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism.

    Directory of Open Access Journals (Sweden)

    Sriram Devanathan

    Full Text Available Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM. While numerous reports have demonstrated increased myocardial fatty acid (FA utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET to estimate myocardial blood flow (MBF and myocardial FA metabolism. Echocardiograms (ECHOs were performed to assess cardiac function. Levels of triglycerides (TG and non-esterified fatty acids (NEFA were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI and decrease in peak early diastolic mitral annular velocity (E' compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

  1. Metabolism of Fructophilic Lactic Acid Bacteria Isolated from the Apis mellifera L. Bee Gut: Phenolic Acids as External Electron Acceptors

    Science.gov (United States)

    Filannino, Pasquale; Addante, Rocco; Pontonio, Erica; Gobbetti, Marco

    2016-01-01

    ABSTRACT Fructophilic lactic acid bacteria (FLAB) are strongly associated with the gastrointestinal tracts (GITs) of Apis mellifera L. worker bees due to the consumption of fructose as a major carbohydrate. Seventy-seven presumptive lactic acid bacteria (LAB) were isolated from GITs of healthy A. mellifera L. adults, which were collected from 5 different geographical locations of the Apulia region of Italy. Almost all of the isolates showed fructophilic tendencies: these isolates were identified as Lactobacillus kunkeei (69%) or Fructobacillus fructosus (31%). A high-throughput phenotypic microarray targeting 190 carbon sources was used to determine that 83 compounds were differentially consumed. Phenotyping grouped the strains into two clusters, reflecting growth performance. The utilization of phenolic acids, such as p-coumaric, caffeic, syringic, or gallic acids, as electron acceptors was investigated in fructose-based medium. Almost all FLAB strains showed tolerance to high phenolic acid concentrations. p-Coumaric acid and caffeic acid were consumed by all FLAB strains through reductases or decarboxylases. Syringic and gallic acids were partially metabolized. The data collected suggest that FLAB require external electron acceptors to regenerate NADH. The use of phenolic acids as external electron acceptors by the 4 FLAB showing the highest phenolic acid reductase activity was investigated in glucose-based medium supplemented with p-coumaric acid. Metabolic responses observed through a phenotypic microarray suggested that FLAB may use p-coumaric acid as an external electron acceptor, enhancing glucose dissimilation but less efficiently than other external acceptors such as fructose or pyruvic acid. IMPORTANCE Fructophilic lactic acid bacteria (FLAB) remain to be fully explored. This study intends to link unique biochemical features of FLAB with their habitat. The quite unique FLAB phenome within the group lactic acid bacteria (LAB) may have practical relevance

  2. Differential induction of peroxisomal beta-oxidation enzymes by clofibric acid and aspirin in piglet tissues.

    Science.gov (United States)

    Yu, X X; Odle, J; Drackley, J K

    2001-11-01

    Peroxisomal beta-oxidation (POX) of fatty acids is important in lipid catabolism and thermogenesis. To investigate the effects of peroxisome proliferators on peroxisomal and mitochondrial beta-oxidation in piglet tissues, newborn pigs (1-2 days old) were allowed ad libitum access to milk replacer supplemented with 0.5% clofibric acid (CA) or 1% aspirin for 14 days. CA increased ratios of liver weight to body weight (P < 0.07), kidney weight to body weight (P < 0.05), and heart weight to body weight (P < 0.001). Aspirin decreased daily food intake and final body weight but increased the ratio of heart weight to body weight (P < 0.01). In liver, activities of POX, fatty acyl-CoA oxidase (FAO), total carnitine palmitoyltransferase (CPT), and catalase were 2.7-, 2.2-, 1.5-fold, and 33% greater, respectively, for pigs given CA than for control pigs. In heart, these variables were 2.2-, 4.1-, 1.9-, and 1.8-fold greater, respectively, for pigs given CA than for control pigs. CA did not change these variables in either kidney or muscle, except that CPT activity was increased approximately 110% (P < 0.01) in kidney. Aspirin increased only hepatic FAO and CPT activities. Northern blot analysis revealed that CA increased the abundance of catalase mRNA in heart by approximately 2.2-fold. We conclude that 1) POX and CPT in newborn pigs can be induced by peroxisomal proliferators with tissue specificity and 2) the relatively smaller induction of POX in piglets (compared with that in young or adult rodents) may be related to either age or species differences.

  3. 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.

  4. GCN2-Dependent Metabolic Stress Is Essential for Endotoxemic Cytokine Induction and Pathology

    Science.gov (United States)

    Liu, Haiyun; Huang, Lei; Bradley, Jillian; Liu, Kebin; Bardhan, Kankana; Ron, David; Mellor, Andrew L.; Munn, David H.

    2014-01-01

    Activated inflammatory macrophages can express indoleamine 2,3-dioxygenase (IDO) and thus actively deplete their own tryptophan supply; however, it is not clear how amino acid depletion influences macrophage behavior in inflammatory environments. In this report, we demonstrate that the stress response kinase GCN2 promotes macrophage inflammation and mortality in a mouse model of septicemia. In vitro, enzymatic amino acid consumption enhanced sensitivity of macrophages to the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) with significantly increased interleukin 6 (IL-6) production. Tryptophan withdrawal induced the stress response proteins ATF4 and CHOP/GADD153; however, LPS stimulation rapidly enhanced expression of both proteins. Moreover, LPS-driven cytokine production under amino acid-deficient conditions was dependent on GCN2, as GCN2 knockout (GCN2KO) macrophages had a significant reduction of cytokine gene expression after LPS stimulation. To test the in vivo relevance of these findings, monocytic-lineage-specific GCN2KO mice were challenged with a lethal dose of LPS intraperitoneally (i.p.). The GCN2KO mice showed reduced inflammatory responses, with decreased IL-6 and IL-12 expression correlating with significant reduction in animal mortality. Thus, the data show that amino acid depletion stress signals (via GCN2) synergize with proinflammatory signals to potently increase innate immune responsiveness. PMID:24248597

  5. [Roles of organic acid metabolism in plant adaptation to nutrient deficiency and aluminum toxicity stress].

    Science.gov (United States)

    Wang, Jianfei; Shen, Qirong

    2006-11-01

    Organic acids not only act as the intermediates in carbon metabolism, but also exert key roles in the plant adaptation to nutrient deficiency and metal stress and in the plant-microbe interactions at root-soil interface. From the viewpoint of plant nutrition, this paper reviewed the research progress on the formation and physiology of organic acids in plant, and their functions in nitrogen metabolism, phosphorus and iron uptake, aluminum tolerance, and soil ecology. New findings in the membrane transport of organic acids and the biotechnological manipulation of organic acids in transgenic model were also discussed. This novel perspectives of organic acid metabolism and its potential manipulation might present a possibility to understand the fundamental aspects of plant physiology, and lead to the new strategies to obtain crop varieties better adapted to environmental and metal stress.

  6. Engineering the fatty acid metabolic pathway in Saccharomyces cerevisiae for advanced biofuel production

    Directory of Open Access Journals (Sweden)

    Xiaoling Tang

    2015-12-01

    Full Text Available Fatty acid-derived fuels and chemicals have attracted a great deal of attention in recent decades, due to their following properties of high compatibility to gasoline-based fuels and existing infrastructure for their direct utilization, storage and distribution. The yeast Saccharomyces cerevisiae is the ideal biofuel producing candidate, based on the wealth of available genetic information and versatile tools designed to manipulate its metabolic pathways. Engineering the fatty acid metabolic pathways in S. cerevisiae is an effective strategy to increase its fatty acid biosynthesis and provide more pathway precursors for production of targeted products. This review summarizes the recent progress in metabolic engineering of yeast cells for fatty acids and fatty acid derivatives production, including the regulation of acetyl-CoA biosynthesis, NADPH production, fatty acid elongation, and the accumulation of activated precursors of fatty acids for converting enzymes. By introducing specific enzymes in the engineered strains, a powerful platform with a scalable, controllable and economic route for advanced biofuel production has been established. Keywords: Metabolic engineering, Fatty acid biosynthesis, Fatty acid derivatives, Saccharomyces cerevisiae

  7. Occurrence and metabolism of 7-hydroxy-2-indolinone-3-acetic acid in Zea mays

    Science.gov (United States)

    Lewer, P.; Bandurski, R. S.

    1987-01-01

    7-Hydroxy-2-indolinone-3-acetic acid was identified as a catabolite of indole-3-acetic acid in germinating kernels of Zea mays and found to be present in amounts of ca 3.1 nmol/kernel. 7-Hydroxy-2-indolinone-3-acetic acid was shown to be a biosynthetic intermediate between 2-indolinone-3-acetic acid and 7-hydroxy-2-indolinone-3-acetic acid-7'-O-glucoside in both kernels and roots of Zea mays. Further metabolism of 7-hydroxy-2-[5-3H]-indolinone-3-acetic acid-7'-O-glucoside occurred to yield tritiated water plus, as yet, uncharacterized products.

  8. Alteration of tricarboxylic acid cycle metabolism in rat brain slices by halothane

    International Nuclear Information System (INIS)

    Cheng, S.C.; Brunner, E.A.

    1978-01-01

    Metabolism of [2- 14 C] pyruvate, [1- 14 C] acetate and [5- 14 C] citrate in rat cerebral cortex slices was studied in the presence of halothane. Metabolites assayed include acetylcholine (ACh), citrate, glutamate, glutamineγ-aminobutyrate (GABA) and aspartate. The trichloroacetic acid soluble extract, the trichloracetic acid insoluble precipitate and its lipid extract were also studied. In control experiments, pyruvate preferentially labelled ACh, citrate, glutamate, GABA and aspartate. Acetate labelled ACh, but to a lesser extent than pyruvate. Acetate also labelled lipids and glutamine. Citrate labelled lipids but not ACh and served as a preferential precursor for glutamine. These data support a three-compartment model for cerebral tricarboxylic acid cycle metabolism. Halothane caused increases in GABA and aspartate contents and a decrease in ACh content. It has no effect on the contents of citrate, glutamate and glutamine. Halothane preferentially inhibited the metabolic transfer of radioactivity from pyruvate into almost all metabolites, an effect probably not related to pyruvate permeability. This is interpreted as halothane depression of the large metabolic compartment which includes the nerve endings. Halothane increased the metabolic transfer of radioactivity from acetate into lipids but did not alter such a transfer into the trichloroacetic acid extract. Halothane increased the metabolic transfer of radioactivity from citrate into the trichloroacetic acid precipitate, lipids and especially glutamine. Transfer of citrate radioactivity into GABA was somewhat decreased. The differential effects of halothane on acetate and citrate utilization suggest that the small metabolic compartment should be subdivided. Therefore, at least three metabolic compartments are demonstrated. Halothane did not interfere with the dicarboxylic acid portion of the tricarboxylic acid cycle. (author)

  9. Metabollic Engineering of Saccharomyces Cereviae a,omi acid metabolism for production of products of industrial interest

    DEFF Research Database (Denmark)

    Chen, Xiao

    -based processes. This study has focused on metabolic engineering of the amino acid metabolism in S. cerevisiae for production of two types of chemicals of industrial interest. The first chemical is δ-(L-α-aminoadipyl)–L-cysteinyl–D-valine (LLD-ACV). ACV belongs to non-ribosomal peptides (NRPs), which......Saccharomyces cerevisiae is widely used in microbial production of chemicals, metabolites and proteins, mainly because genetic manipulation of S. cerevisiae is relatively easy and experiences from its wide application in the existing industrial fermentations directly benefit new S. cerevisiae...

  10. Simultaneous analysis of amino acid and organic acid by NMR spectrometry, 2. Diagnostic aids for inborn error of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Koda, Naoya; Yamaguchi, Shuichi; Mori, Takeshi.

    1987-09-01

    Analysis of urine from patients with inborn error of metabolism were studied by /sup 1/H-nuclear magnetic resonance (NMR) spectrometry. Diseases studied were as follows; phenylketonuria, biotin responsive multiple carboxylase deficiency, non-ketotic hyperglycinemia, 3-ketothiolase deficiency, alkaptonuria, methylmalonic acidemia, isovaleric acidemia, glutaric aciduria, argininosuccinic aciduria and hyperornithinemia. In each disease, specific metabolites in urine were recognized by NMR spectrometry. This method is accomplished within 10 minutes with non-treated small volume of urine and will be successfully available for the screening andor diagnosis of inherited metabolic diseases of amino acid and organic acid.

  11. 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.

  12. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M

    2017-01-01

    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohep......The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...... enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes...... such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus...

  13. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    Science.gov (United States)

    Peluso, Ilaria; Romanelli, Luca; Palmery, Maura

    2014-05-01

    The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment.

  14. The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

    NARCIS (Netherlands)

    Demetz, Egon; Schroll, Andrea; Auer, Kristina; Heim, Christiane; Patsch, Josef R.; Eller, Philipp; Theurl, Markus; Theurl, Igor; Theurl, Milan; Seifert, Markus; Lener, Daniela; Stanzl, Ursula; Haschka, David; Asshoff, Malte; Dichtl, Stefanie; Nairz, Manfred; Huber, Eva; Stadlinger, Martin; Moschen, Alexander R.; Li, Xiaorong; Pallweber, Petra; Scharnagl, Hubert; Stojakovic, Tatjana; Maerz, Winfried; Kleber, Marcus E.; Garlaschelli, Katia; Uboldi, Patrizia; Catapano, Alberico L.; Stellaard, Frans; Rudling, Mats; Kuba, Keiji; Imai, Yumiko; Arita, Makoto; Schuetz, John D.; Pramstaller, Peter P.; Tietge, Uwe J. F.; Trauner, Michael; Norata, Giuseppe D.; Claudel, Thierry; Hicks, Andrew A.; Weiss, Guenter; Tancevski, Ivan

    2014-01-01

    Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By

  15. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5bet...

  16. Uric acid, an important screening tool to detect inborn errors of metabolism: a case series.

    Science.gov (United States)

    Jasinge, Eresha; Kularatnam, Grace Angeline Malarnangai; Dilanthi, Hewa Warawitage; Vidanapathirana, Dinesha Maduri; Jayasena, Kandana Liyanage Subhashinie Priyadarshika Kapilani Menike; Chandrasiri, Nambage Dona Priyani Dhammika; Indika, Neluwa Liyanage Ruwan; Ratnayake, Pyara Dilani; Gunasekara, Vindya Nandani; Fairbanks, Lynette Dianne; Stiburkova, Blanka

    2017-09-06

    Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.

  17. Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Eoin Barrett

    Full Text Available The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15 were orally gavaged with either B. breve DPC6330 (10(9 microorganisms/day alone or in combination with 0.5% (w/w linoleic acid & 0.5% (w/w α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11 in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05. Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11 in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05, whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05 compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01 and α-linolenic acid in adipose tissue (p<0.001, whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05, and α-linolenic acid in adipose tissue (p<0.001. B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated

  18. Metabolism of fatty acids in rat brain in microsomal membranes

    International Nuclear Information System (INIS)

    Aeberhard, E.E.; Gan-Elepano, M.; Mead, J.F.

    1980-01-01

    Using a technique in which substrate fatty acids are incorporated into microsomal membranes followd by comparison of their rates of desaturation or elongation with those of exogenous added fatty acids it has been found that the desaturation rate is more rapid for the membrane-bound substrate than for the added fatty acid. Moreover, the product of the membrane-bound substrate is incorporated into membrane phospholipid whereas the product of the exogenous substrate is found in di- and triacyl glycerols and in free fatty acids as well. These and other findings point to a normal sequence of reaction of membrane liqids with membrane-bound substrates involving transfer of fatty acid from phospholipid to the coupled enzyme systems without ready equilibration with the free fatty acid pool

  19. Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human.

    Science.gov (United States)

    Tremblay-Franco, Marie; Zerbinati, Chiara; Pacelli, Antonio; Palmaccio, Giuseppina; Lubrano, Carla; Ducheix, Simon; Guillou, Hervé; Iuliano, Luigi

    2015-07-01

    Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human. In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids. 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection. We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis. Our data provide the first evidence that obesity and metabolic syndrome are associated with

  20. Hepatic Metabolism of Perfluorinated Carboxylic Acids and Polycholorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in Vivo

    Science.gov (United States)

    1993-01-14

    I14JAN93 Annual Technical Report 15DEC91-1ý+JAN9 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Hepatic Metabolism of Perfluorinated Carboxylic Acids and G-FS...13. ABSTRACT (Maximum 200 words) This report describes our studies of the effects of perfluorooctanoic acid (PFOA) and perfluorodecanolc acid (PFDA) on...metabolism. 31 p NMR was used to examine the effects of PFDA. PFOA. and clofibrate (C LOF) in both rats and guinea pigs. A unique effect is revealed in

  1. Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

    International Nuclear Information System (INIS)

    Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

    2009-01-01

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  2. Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

    Science.gov (United States)

    Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

    2009-06-15

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  3. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

    DEFF Research Database (Denmark)

    Hoeft, B.; Linseisen, J.; Beckmann, L.

    2010-01-01

    as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred......Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

  4. Nitrogen and amino acid metabolism in dairy cows

    NARCIS (Netherlands)

    Tamminga, S.

    1981-01-01

    For the process of milk production, the dairy cow requires nutrients of which energy supplying nutrients and protein or amino acid supplying nutrients are the most important. Amino acid supplying nutrients have to be absorbed from the small intestine and the research reported in this thesis mainly

  5. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    Science.gov (United States)

    Lassandro, Carlotta; Banderali, Giuseppe; Radaelli, Giovanni; Borghi, Elisa; Moretti, Francesca; Verduci, Elvira

    2015-08-21

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.

  6. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    Directory of Open Access Journals (Sweden)

    Carlotta Lassandro

    2015-08-01

    Full Text Available Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF criteria has been suggested in children. Docosahexaenoic acid (DHA has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.

  7. The gut microbiota modulates host amino acid and glutathione metabolism in mice

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias

    2015-01-01

    , liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism...... conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon....... To validate our predictions, we measured the level of AAs and N-acetylated AAs in the hepatic portal vein of CONV-R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV-R and GF mice accounting for the content of the diet and relative gene expression differences...

  8. Effect of salicylic acid on the growth photosynthesis and carbohydrate metabolism in salt stressed maize plants

    International Nuclear Information System (INIS)

    Moussa, H.R.; Khodary, S.E.A.

    2003-01-01

    Aqueous solutions of salicylic acid as a spray to Na CI-treated corn (Zea mays L,) significantly increased the growth of shoots and roots as measured after seven days of treatment. Spraying of salicylic acid caused significant increases in the activity of both ribulose 1,5 bisphosphate carboxylase (rubisco) enzyme and photosynthetic pigments. Moreover, salicylic acid treatment induced high values of soluble carbohydrate fractions in salt stressed plants as compared with salicylic acid treated samples. These data suggest that salicylic acid might improve the growth pattern of NaCl-treated maize plants via increasing the rate of photosynthesis and carbohydrate metabolism

  9. Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism.

    Science.gov (United States)

    Hou, Entai; Li, Xian; Liu, Zerong; Zhang, Fuchang; Tian, Zhongmin

    2018-04-01

    Fumarase catalyzes the interconversion of fumarate and l-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l-malic acid, l-aspartic acid, glycine and l-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics

    Science.gov (United States)

    2013-01-01

    Background Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results Supplementation with several EO/BO combinations increased circulating 20–22 carbon (20–22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%. Conclusions This study shows that dietary supplementation with BO/EO alters 20–22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation. PMID:24088297

  11. Contributions of Cell Metabolism and H+ Diffusion to the Acidic pH of Tumors

    Directory of Open Access Journals (Sweden)

    Paul A. Schornack

    2003-03-01

    Full Text Available The tumor microenvironment is hypoxic and acidic. These conditions have a significant impact on tumor progression and response to therapies. There is strong evidence that tumor hypoxia results from inefficient perfusion due to a chaotic vasculature. Consequently, some tumor regions are well oxygenated and others are hypoxic. It is commonly believed that hypoxic regions are acidic due to a stimulation of glycolysis through hypoxia, yet this is not yet demonstrated. The current study investigates the causes of tumor acidity by determining acid production rates and the mechanism of diffusion for H+ equivalents through model systems. Two breast cancer cell lines were investigated with divergent metabolic profiles: nonmetastatic MCF-7/s and highly metastatic MDA-mb-435 cells. Glycolysis and acid production are inhibited by oxygen in MCF-7/s cells, but not in MDA-mb-435 cells. Tumors of MDAmb-435 cells are significantly more acidic than are tumors of MCF-7/s cells, suggesting that tumor acidity is primarily caused by endogenous metabolism, not the lack of oxygen. Metabolically produced protons are shown to diffuse in association with mobile buffers, in concordance with previous studies. The metabolic and diffusion data were analyzed using a reaction-diffusion model to demonstrate that the consequent pH profiles conform well to measured pH values for tumors of these two cell lines.

  12. Engineering of aromatic amino acid metabolism in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Vuralhan, Z.

    2006-01-01

    Saccharomyces cerevisiae is a popular industrial microorganism. It has since long been used in bread, beer and wine making. More recently it is also being applied for heterologous protein production and as a target organism for metabolic engineering. The work presented in this thesis describes how

  13. New insights into the metabolism of aspartate-family amino acids in plant seeds.

    Science.gov (United States)

    Wang, Wenyi; Xu, Mengyun; Wang, Guoping; Galili, Gad

    2018-02-05

    Aspartate-family amino acids. Aspartate (Asp)-family pathway, via several metabolic branches, leads to four key essential amino acids: Lys, Met, Thr, and Ile. Among these, Lys and Met have received the most attention, as they are the most limiting amino acid in cereals and legumes crops, respectively. The metabolic pathways of these four essential amino acids and their interactions with regulatory networks have been well characterized. Using this knowledge, extensive efforts have been devoted to augmenting the levels of these amino acids in various plant organs, especially seeds, which serve as the main source of human food and livestock feed. Seeds store a number of storage proteins, which are utilized as nutrient and energy resources. Storage proteins are composed of amino acids, to guarantee the continuation of plant progeny. Thus, understanding the seed metabolism, especially with respect to the accumulation of aspartate-derived amino acids Lys and Met, is a crucial factor for sustainable agriculture. In this review, we summarized the Asp-family pathway, with some new examples of accumulated Asp-family amino acids, particularly Lys and Met, in plant seeds. We also discuss the recent advances in understanding the roles of Asp-family amino acids during seed development.

  14. Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

    Energy Technology Data Exchange (ETDEWEB)

    Hagland, Hanne R.; Nilsson, Linn I.H. [Department of Biomedicine, University of Bergen (Norway); Burri, Lena [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Nikolaisen, Julie [Department of Biomedicine, University of Bergen (Norway); Berge, Rolf K. [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Department of Heart Disease, Haukeland University Hospital (Norway); Tronstad, Karl J., E-mail: karl.tronstad@biomed.uib.no [Department of Biomedicine, University of Bergen (Norway)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.

  15. Study on the metabolism of 15 p-131iodine phenyl pentadecanoic acid [p-iodine phenyl pentadecanoic acid] as a tracer of free fatty acids in comparison to 1-14C-palmitic acid (C-palmitic acid)

    International Nuclear Information System (INIS)

    Sauer, J.W.

    1986-01-01

    In an animal experiment under identical metabolic influences the metabolism of a new radiopharmaceutical, 15 p- 131 iodine phenyl pentadecanoic acid (IPPA), was compared to the marked physiological fatty acid, 1- 14 C-palmitic acid (PA). The pharmacological kinetics of both tracers in tissues with widely varied turnover rates of fatty acids (heart, lung, liver, kidney, spleen, small intestine, skeletal muscle) was studied. By alkali extraction of the tissue lipids and then a chromatographic separation of the lipid fractions quantitatively comparable statements about the metabolism of PA and IPPA were made possible. The analyses of autoradiographs of the chromatographically separated lipids show a qualitatively congruous assimilation of both markers in the major lipid fractions. The quantitative evaluation shows minor differences as a result of a preferred assimilation of IPPA in triglycerides and of PA in phospholipids. The fractionated separation of tissue lipids which had been marked with PA and IPPA in vivo agrees very well with values which have been determined by other authors using 14 C- or 3 H-marked fatty acids. The close correlation of the tissue-specific metabolism kinetics of both markers makes it clear that both fatty acids are metabolized by similar, respectively, primarily identical metabolic pathyways. In conclusion, this study makes clear the extensive congruence of the metabolism kinetics of IPPA and the kinetics of the physiological palmitic acid. As a result of the presented results of the γ-radiating radiopharmaceutical IPPA as a free fatty acid analog new possibilities for the non-invasive external comprehension of lipid metabolism are opened up, whose use especially in the diagnostic of heart diseases promises success. (orig./MG) [de

  16. Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure

    Directory of Open Access Journals (Sweden)

    Chang Liu

    2018-03-01

    Full Text Available Background: The modulation of arachidonic acid (AA metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS model.Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA after integrating metabolic information with phenotypic and transcriptomic datasets, respectively.Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS, metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively

  17. Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Yingying; Chen, Xi; Yu, Dehai [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Tao [Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Cui, Jiuwei; Wang, Guanjun [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Hu, Ji-Fan, E-mail: jifan@stanford.edu [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Wei, E-mail: jdyylw@163.com [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China)

    2015-09-10

    Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.

  18. Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination

    International Nuclear Information System (INIS)

    Luethy, P.C.; Chatelain, P.; Papageorgiou, I.; Schubiger, A.; Lerch, R.A.

    1988-01-01

    Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs

  19. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    International Nuclear Information System (INIS)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

    2013-01-01

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA

  20. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  1. Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

    International Nuclear Information System (INIS)

    Thomas, G.; Pepin, D.; Loriette, C.; Chambaz, J.; Bereziat, G.; Vidal, M.; Apparu, M.; Coornaert, S.

    1989-01-01

    The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be β oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be β oxidized only after an initial α oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me 2 ) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me 2 ) which cannot be β oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1- 14 C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethyl-branched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[ 125 I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1- 14 C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched palmitic acids were found in hepatocyte or secreted phospholipids as compared with palmitic acid. (orig.)

  2. Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics.

    Science.gov (United States)

    Mu, Chunlong; Yang, Yuxiang; Yu, Kaifan; Yu, Miao; Zhang, Chuanjian; Su, Yong; Zhu, Weiyun

    2017-04-01

    In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.

  3. Energy metabolism in Mycobacterium gilvum PYR-GCK: insights from transcript expression analyses following two states of induction.

    Directory of Open Access Journals (Sweden)

    Abimbola Comfort Badejo

    Full Text Available Mycobacterium gilvum PYR-GCK, a pyrene degrading bacterium, has been the subject of functional studies aimed at elucidating mechanisms related to its outstanding pollutant bioremediation/biodegradation activities. Several studies have investigated energy production and conservation in Mycobacterium, however, they all focused on the pathogenic strains using their various hosts as induction sources. To gain greater insight into Mycobacterium energy metabolism, mRNA expression studies focused on respiratory functions were performed under two different conditions using the toxic pollutant pyrene as a test substrate and glucose as a control substrate. This was done using two transcriptomic techniques: global transcriptomic RNA-sequencing and quantitative Real-Time PCR. Growth in the presence of pyrene resulted in upregulated expression of genes associated with limited oxygen or anaerobiosis in M. gilvum PYR-GCK. Upregulated genes included succinate dehydrogenases, nitrite reductase and various electron donors including formate dehydrogenases, fumarate reductases and NADH dehydrogenases. Oxidative phosphorylation genes (with respiratory chain complexes I, III -V were expressed at low levels compared to the genes coding for the second molecular complex in the bacterial respiratory chain (fumarate reductase; which is highly functional during microaerophilic or anaerobic bacterial growth. This study reveals a molecular adaptation to a hypoxic mode of respiration during aerobic pyrene degradation. This is likely the result of a cellular oxygen shortage resulting from exhaustion of the oxygenase enzymes required for these degradation activities in M. gilvum PYR-GCK.

  4. Effect of extracellular fatty acids on lipid metabolism in cultured rabbit articular chondrocytes

    International Nuclear Information System (INIS)

    Nagao, M.; Ishii, S.; Murata, Y.; Akino, T.

    1991-01-01

    Rabbit articular chondrocytes were cultured for 8 h in the presence of various concentrations (5-500 microM) of 14 C oleic, 14 C linoleic, and 3H arachidonic acids. The radioactive unsaturated fatty acids were incorporated into triacylglycerol (TG) and phosphatidylcholine (PC) in a concentration-dependent manner; more fatty acids were incorporated into TG than into PC, at higher concentrations of extracellular fatty acids. Among these fatty acids, arachidonic acid was incorporated into TG much more than into PC, in spite of a very low concentration of arachidonic acid in TG. After transfer of the labeled cells to maintenance medium, the radioactivity in TG declined rapidly and 3 H arachidonic acid radioactivity in PC increased continuously during the chase time periods. Palmitoyl-unsaturated species were mainly formed in PC when cultured at a concentration of 5 microM of each fatty acid. However, when cultured at 500 microM, unsaturated-unsaturated species, specific for each unsaturated fatty acid were actively formed. These findings indicate that (1) fatty acid composition of TG and PC in articular chondrocytes is influenced by the degree of fatty acid supply, (2) formation and turnover of TG plays a role in fatty acid metabolism of cells, and (3) fatty acid pairing in PC is modulated by extracellular fatty acid concentrations

  5. Oxidative metabolism of 5-o-caffeoylquinic acid (chlorogenic acid), a bioactive natural product, by metalloporphyrin and rat liver mitochondria.

    Science.gov (United States)

    dos Santos, Michel D; Martins, Patrícia R; dos Santos, Pierre A; Bortocan, Renato; Iamamoto, Y; Lopes, Norberto P

    2005-09-01

    Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimic the various reactions of cytochrome P450 enzymes systems in the oxidation and oxygenation of various drugs and biologically active compounds. This paper reports an HPLC-MS-MS investigation of chlorogenic acid (CGA) oxidation by iodosylbenzene using iron(III) tetraphenylporphyrin chloride as catalyst. The oxidation products have been detected by sequential MS analyses. In addition, CGA was submitted to an in vitro metabolism assay employing isolated rat liver mitochondria. The single oxidized product obtained from mitochondrial metabolism corresponds to the major product formed by the metalloporphyrin-catalyzed reaction. These results indicate that biomimetic oxidation reactions, in addition to in vitro metabolism assays employing isolated organs/organelles, could replace some in vivo metabolism studies, thus minimizing the problems related to the use of a large number of living animals in experimental research.

  6. Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health

    Directory of Open Access Journals (Sweden)

    J. Bruce German

    2011-07-01

    Full Text Available This article focuses on the role of omega-3 fatty acids as precursors for lipid signaling molecules known as oxylipins. Although omega-3 fatty acids are beneficial in autoimmune disorders, inflammatory diseases and heart disease, they are generally underrepresented in the American diet. A literature review confirms that the consumption of omega-3 fatty acids - whether in food sources such as walnuts, flax seeds and fatty fish (including salmon and sardines, or in supplements - is associated with decreased morbidity and mortality. This growing body of evidence, including the results of a recent study of patients with kidney disease, highlights the need to measure omega-3 fatty acids and their oxylipin products as markers of metabolic health and biomarkers of disease. In addition, there is substantial evidence of the need to increase the omega-3 fatty acid content of American diets to optimize metabolic health.

  7. Arachidonic acid metabolism in fibroblasts derived from canine myocardium

    International Nuclear Information System (INIS)

    Weber, D.R.; Prescott, S.M.

    1986-01-01

    Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p 3 H]arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 μM) caused release and metabolism of [ 3 H] AA. A23187 or AA (10μM) induced production of 6-keto PGF1α, PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1α showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p 3 H]AA released but did not metabolize [ 3 H]AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1α, PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event

  8. 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

  9. NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation

    International Nuclear Information System (INIS)

    Pan, Tao; Zhang, Mei; Zhang, Fang; Yan, Guang; Ru, Yi; Wang, Qinhao; Zhang, Yao; Wei, Xuehui; Xu, Xinyuan; Shen, Lan; Zhang, Jian; Wu, Kaichun; Yao, Libo; Li, Xia

    2017-01-01

    Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation. Moreover, NDRG2 overexpression aggravated energy imbalance and oxidative stress by decreasing the intracellular ATP and NADPH generation and increasing ROS levels. Strikingly, NDRG2 inhibited the activation of fatty acid oxidation (FAO), which preserves ATP and NADPH purveyance in the absence of glucose. Finally, mechanistic investigation showed that NDRG2 overexpression suppressed the glucose-deprivation induced AMPK/ACC pathway activation in hepatoma cells, whereas the expression of a constitutively active form of AMPK abrogated glucose-deprivation induced AMPK activation and cell apoptosis. Thus, as a negative regulator of AMPK, NDRG2 disturbs the induction of FAO genes by glucose limitation, leading to dysregulation of ATP and NADPH, and thus reduces the tolerance of hepatoma cells to glucose limitation. - Highlights: • NDRG2 overexpression reduces the tolerance of hepatoma cells to glucose limitation. • NDRG2 overexpression aggravates energy imbalance and oxidative stress under glucose deprivation. • NDRG2 overexpression disturbs the activation of FAO in hepatoma cells under glucose limitation. • NDRG2 overexpression inhibits the activation of AMPK/ACC pathway in hepatoma cells during glucose starvation.

  10. Metabolism and excretion of orally and intraperitoneally administered methylarsonic acid in the hamster

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, H.; Yamato, N.; Yamamura, Y.

    1988-02-01

    A number of investigators have demonstrated that when inorganic arsenic is administered to humans and experimental animals, methylarsonic acid (MAA) is formed in vivo. Low concentrations of MAA have been detected in human organs and urine. Few studies of the metabolism and elimination of MAA have been published. Following administration of a single oral dose of MAA to human subject, it was reported that MAA was rapidly metabolized to dimethylarsinic acid (DMAA) in vivo and excreted in urine. While the elimination of MAA has been investigated experimentally in animals, nothing is known of MAA metabolism and distribution in vivo. In the present study, the metabolism of MAA was investigated following its administration to hamsters. Arsenic species deposited in selected organs and blood, and the amounts and chemical species of arsenic excreted in urine and feces were determined.

  11. 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 ...

  12. Mass spectrometry characterisation of fatty acids from metabolically engineered soybean seeds.

    Science.gov (United States)

    Murad, André M; Vianna, Giovanni R; Machado, Alex M; da Cunha, Nicolau B; Coelho, Cíntia M; Lacerda, Valquiria A M; Coelho, Marly C; Rech, Elibio L

    2014-05-01

    Improving the quality and performance of soybean oil as biodiesel depends on the chemical composition of its fatty acids and requires an increase in monounsaturated acids and a reduction in polyunsaturated acids. Despite its current use as a source of biofuel, soybean oil contains an average of 25 % oleic acid and 13 % palmitic acid, which negatively impacts its oxidative stability and freezing point, causing a high rate of nitrogen oxide emission. Gas chromatography and ion mobility mass spectrometry were conducted on soybean fatty acids from metabolically engineered seed extracts to determine the nature of the structural oleic and palmitic acids. The soybean genes FAD2-1 and FatB were placed under the control of the 35SCaMV constitutive promoter, introduced to soybean embryonic axes by particle bombardment and down-regulated using RNA interference technology. Results indicate that the metabolically engineered plants exhibited a significant increase in oleic acid (up to 94.58 %) and a reduction in palmitic acid (to seed oil content. No structural differences were observed between the fatty acids of the transgenic and non-transgenic oil extracts.

  13. Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chao; Cao, Yujin; Zou, Huibin; Xian, Mo [Chinese Academy of Sciences, Qingdao (China). Key Lab. of Biofuels

    2011-02-15

    Confronted with the gradual and inescapable exhaustion of the earth's fossil energy resources, the bio-based process to produce platform chemicals from renewable carbohydrates is attracting growing interest. Escherichia coli has been chosen as a workhouse for the production of many valuable chemicals due to its clear genetic background, convenient to be genetically modified and good growth properties with low nutrient requirements. Rational strain development of E. coli achieved by metabolic engineering strategies has provided new processes for efficiently biotechnological production of various high-value chemical building blocks. Compared to previous reviews, this review focuses on recent advances in metabolic engineering of the industrial model bacteria E. coli that lead to efficient recombinant biocatalysts for the production of high-value organic acids like succinic acid, lactic acid, 3-hydroxypropanoic acid and glucaric acid as well as alcohols like 1,3-propanediol, xylitol, mannitol, and glycerol with the discussion of the future research in this area. Besides, this review also discusses several platform chemicals, including fumaric acid, aspartic acid, glutamic acid, sorbitol, itaconic acid, and 2,5-furan dicarboxylic acid, which have not been produced by E. coli until now. (orig.)

  14. Kynurenine acid - metabolism and regulation of kynurenine pathway

    Directory of Open Access Journals (Sweden)

    Piotr Kozłowski

    2017-07-01

    Full Text Available Kynurenic acid (KYNA was first isolated from the dog's urine in 1853 by german chemist Justus von Liebig. KYNA probably plays an important role in the pathogenesis of many neurodegenerative and psychiatric diseases. Its elevated concentration were found in the brain (post mortem or in the cerebrospinal fluid patients  with schizophrenia, bipolar disorder, Alzheimer's disease, meningitis, autoimmune diseases, inflammatory processes and memory and learning disorders. The reduced KYNA concentration is characteristic for multiple sclerosis, Parkinson's disease, Huntington's disease and epilepsy. KYNA is an organic compound naturally occurring in nature. This amino acid belongs to the group of exogenous amino acids and can be synthesized by plants and bacteria alone. The largest amount of tryptophan about 95%is  metabolised by the kynurenine pathway. Only 1% of tryptophan supplied in the diet serves to produce serotonin in the brain. The process of regulation of KYNA synthesis in both the CNS and the periphery is complicated.

  15. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    International Nuclear Information System (INIS)

    Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

    2006-01-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

  16. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Nan [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)]. E-mail: nan.mei@fda.hhs.gov; Arlt, Volker M. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Phillips, David H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Heflich, Robert H. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Chen, Tao [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)

    2006-12-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by {sup 32}P-postlabeling and mutant frequency (MF) was determined using the {lambda} Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N {sup 6}-yl]-aristolactam I, 7-[deoxyadenosin-N {sup 6}-yl]-aristolactam II and 7-[deoxyguanosin-N {sup 2}-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10{sup 8} nucleotides in liver and 95-4598 adducts/10{sup 8} nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10{sup -6} in liver compared with the MFs of 78-1319 x 10{sup -6} that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T {sup {yields}} T:A transversion was the predominant mutation in AA-treated rats; whereas G:C {sup {yields}} A:T transition was the main type of mutation in control

  17. Anaerobic organic acid metabolism of Candida zemplinina in comparison with Saccharomyces wine yeasts.

    Science.gov (United States)

    Magyar, Ildikó; Nyitrai-Sárdy, Diána; Leskó, Annamária; Pomázi, Andrea; Kállay, Miklós

    2014-05-16

    Organic acid production under oxygen-limited conditions has been thoroughly studied in the Saccharomyces species, but practically never investigated in Candida zemplinina, which seems to be an acidogenic species under oxidative laboratory conditions. In this study, several strains of C. zemplinina were tested for organic acid metabolism, in comparison with Saccharomyces cerevisiae, Saccharomyces uvarum and Candida stellata, under fermentative conditions. Only C. stellata produced significantly higher acidity in simple minimal media (SM) with low sugar content and two different nitrogen sources (ammonia or glutamic acid) at low level. However, the acid profile differed largely between the Saccharomyces and Candida species and showed inverse types of N-dependence in some cases. Succinic acid production was strongly enhanced on glutamic acid in Saccharomyces species, but not in Candida species. 2-oxoglutarate production was strongly supported on ammonium nitrogen in Candida species, but remained low in Saccharomyces. Candida species, C. stellata in particular, produced more pyruvic acid regardless of N-sources. From the results, we concluded that the anaerobic organic acid metabolisms of C. zemplinina and C. stellata are different from each other and also from that of the Saccharomyces species. In the formation of succinic acid, the oxidative pathway from glutamic acid seems to play little or no role in C. zemplinina. The reductive branch of the TCA cycle, however, produces acidic intermediates (malic, fumaric, and succinic acid) in a level comparable with the production of the Saccharomyces species. An unidentified organic acid, which was produced on glutamic acid only by the Candida species, needs further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Free fatty acids and their metabolism affect function and survival of podocytes

    Directory of Open Access Journals (Sweden)

    Jonas eSieber

    2014-10-01

    Full Text Available Podocyte injury and loss critically contribute to the pathogenesis of proteinuric kidney diseases including diabetic nephropathy. Deregulated lipid metabolism with disturbed free fatty acid (FFA metabolism is a characteristic of metabolically unhealthy obesity and type 2 diabetes and likely contributes to end-stage kidney disease irrespective of the underlying kidney disease. In the current review we summarize recent findings related to FFAs and altered renal FFA metabolism with a special focus on podocytes. We will outline the opposing effects of saturated and monounsaturated FFAs and a particular emphasis will be given to the underlying molecular mechanisms involving insulin resistance and endoplasmic reticulum homeostasis. Finally, recent data suggesting a critical role of renal FFA metabolism to adapt to an altered lipid environment will be discussed.

  19. Effect of some metabolic inhibitors on citric acid production Aspergillus niger

    Energy Technology Data Exchange (ETDEWEB)

    Agrawal, P.K.; Bhatt, C.S.; Viswanathan, L.

    1983-09-01

    Stationary cultures of Aspergillus niger grown on a synthetic medium have been used to study the effect of some metabolic inhibitors on citric acid production. Addition of 0.05 to 1 mM sodium malonate or 0.01 to 0.1 mM potassium ferricyanide, iodoacetate, sodium azide, soldium arsenate or sodium fluoride stimulated citric acid production (3.6 to 45%), but not total titratable acids. Addition of higher concentrations (0.2 to 10 mM) of later inhibitors caused a marked inhibition of fungal growth and citric acid production. The implications of these preliminary findings are discussed. (Refs. 25).

  20. Fatty acids from diet and microbiota regulate energy metabolism [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Joe Alcock

    2015-09-01

    Full Text Available A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.

  1. Correlation of lipid metabolism characteristics with bile acid metabolism and placental hypoxia injury in patients with intrahepatic cholestasis of pregnancy

    Directory of Open Access Journals (Sweden)

    Liang Tang

    2017-05-01

    Full Text Available Objective: To study the correlation of lipid metabolism characteristics with bile acid metabolism and placental hypoxia injury in patients with intrahepatic cholestasis of pregnancy (ICP. Methods: ICP pregnant women and healthy pregnant women who received antenatal care and delivered in Obstetrics Department of Panzhihua Maternal and Child Health Care Hospital between May 2013 and October 2016 were collected and included in ICP group and control group respectively. Serum lipid metabolism and bile acid metabolism indexes were measured at 20 weeks, 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation; mitochondria damage molecule expression levels in placenta were determined after childbirth. Results: Serum TC, LDL-C and HDL-C levels were not different between two groups of pregnant women at 20 weeks of gestation, and serum TC and LDL-C levels of ICP group at 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation were significantly higher than those of control group while HDL-C levels were significantly lower than those of control group; serum TBA, ALT and AST levels were not different between two groups of pregnant women at 20 weeks, 24 weeks and 28 weeks of gestation, and serum TBA, ALT and AST levels of ICP group at 32 weeks and 36 weeks of gestation were significantly higher than those of control group; CCO, ATPase, SDH and Bcl-2 protein expression in placenta tissue of ICP group were significantly lower than those of control group while Bax and Caspase-3 protein expression were significantly higher than those of control group. Serum LDL-C levels at 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation were positively correlated with TBA, ALT and AST levels in serum as well as Bax and Caspase-3 protein expression in placental tissue, and negatively correlated with CCO, ATPase, SDH and Bcl-2 protein expression in placental tissue. Conclusion: Midtrimester lipid metabolism characteristics can early predict the risk of ICP and evaluate the

  2. Nucleic acid metabolism in hemopoietic tissues of polycythemic rats during long-term fractionated irradiation

    International Nuclear Information System (INIS)

    Mushkacheva, G.S.; Murzina, L.D.

    1980-01-01

    A study was made of the effect of long-term fractionated exposure with a daily dose of 50 R on the nucleic acid metabolism in hemopoietic tissues (bone marrow and spleen) of rats with erythropoiesis selectively inhibited by posttransfusion polycythemia. The comparison of present and previously obtained results enables us to conclude that the pathways of changes in the nucleic acid metabolism, which is responsible for hemopoiesis compensation during long-term exposure, are, in the main, similar for both white and red compartments of hemopoiesis

  3. Influence of organic acids and organochlorinated insecticides on metabolism of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Pejin Dušanka J.

    2005-01-01

    Full Text Available Saccharomyces cerevisiae is exposed to different stress factors during the production: osmotic, temperature, oxidative. The response to these stresses is the adaptive mechanism of cells. The raw materials Saccharomyces cerevisiae is produced from, contain metabolism products of present microorganisms and protective agents used during the growth of sugar beet for example the influence of acetic and butyric acid and organochlorinated insecticides, lindan and heptachlor, on the metabolism of Saccharomyces cerevisiae was investigated and presented in this work. The mentioned compounds affect negatively the specific growth rate, yield, content of proteins, phosphorus, total ribonucleic acids. These compounds influence the increase of trechalose and glycogen content in the Saccharomyces cerevisiae cells.

  4. In search of druggable targets for GBM amino acid metabolism

    NARCIS (Netherlands)

    Panosyan, Eduard H.; Lin, Henry J.; Koster, Jan; Lasky, Joseph L.

    2017-01-01

    Background: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database (http://r2.amc.nl) analyses were carried out to screen for such targets among 95 AA related enzymes. Methods: First, we identified the genes that were differentially

  5. Studies of citric acid metabolism in heart muscle

    NARCIS (Netherlands)

    Meduski, J.W.

    1950-01-01

    1. The pentabromoacetone method for the determination of citric acid was studied; a modification of the procedure of Natelson, Lugovoy and Pincus was used. 2. Two tissue preparations were obtained. The first by washing with water, the second by washing with water and then with 0.5% sodium

  6. Induction of cytochromes P450 1A1 and 1A2 suppresses formation of DNA adducts by carcinogenic aristolochic acid I in rats in vivo

    International Nuclear Information System (INIS)

    Dračínská, Helena; Bárta, František; Levová, Kateřina; Hudecová, Alena; Moserová, Michaela; Schmeiser, Heinz H.; Kopka, Klaus; Frei, Eva; Arlt, Volker M.; Stiborová, Marie

    2016-01-01

    Highlights: • Oxidation and reduction of aristolochic acid I (AAI) dictate its (geno)toxicity in vivo. • Cytochrome P450 (CYP) 1A1 and 1A2 are induced in rats treated with Sudan I and AAI. • Induced CYP1A enzyme activity resulted in decreased AAI-DNA adduct levels in vivo. • CYP1A1 and 1A2 mainly detoxify AAI and attenuate its genotoxicity in vivo. - Abstract: Aristolochic acid I (AAI) is a natural plant alkaloid causing aristolochic acid nephropathy, Balkan endemic nephropathy and their associated urothelial malignancies. One of the most efficient enzymes reductively activating AAI to species forming AAI-DNA adducts is cytosolic NAD(P)H:quinone oxidoreductase 1. AAI is also either reductively activated or oxidatively detoxified to 8-hydroxyaristolochic acid (AAIa) by microsomal cytochrome P450 (CYP) 1A1 and 1A2. Here, we investigated which of these two opposing CYP1A1/2-catalyzed reactions prevails in AAI metabolism in vivo. The formation of AAI-DNA adducts was analyzed in liver, kidney and lung of rats treated with AAI, Sudan I, a potent inducer of CYP1A1/2, or AAI after pretreatment with Sudan I. Compared to rats treated with AAI alone, levels of AAI-DNA adducts determined by the 32 P-postlabeling method were lower in liver, kidney and lung of rats treated with AAI after Sudan I. The induction of CYP1A1/2 by Sudan I increased AAI detoxification to its O-demethylated metabolite AAIa, thereby reducing the actual amount of AAI available for reductive activation. This subsequently resulted in lower AAI-DNA adduct levels in the rat in vivo. Our results demonstrate that CYP1A1/2-mediated oxidative detoxification of AAI is the predominant role of these enzymes in rats in vivo, thereby suppressing levels of AAI-DNA adducts.

  7. Folic acid, one-carbon metabolism & childhood cancer

    Directory of Open Access Journals (Sweden)

    Nirmalya Roy Moulik

    2017-01-01

    Full Text Available Folate has been studied in relation to many diseases, especially cancer. Although it has been postulated to exert a dual effect on development of cancer, its role remains to be clearly defined. Its effect on cancer is the result of gene-nutrient interaction between the genes in folate metabolic pathway and dietary folate availability; mutations in genes of folate metabolism have been shown to alter individual susceptibility to certain childhood cancers as well as response to cancer chemotherapy. Although mandatory fortification of food items with folate has been initiated in some countries, many countries are yet to adopt this due to concerns about undesired adverse effects of high folate levels on health, especially cancer. However, initial reports suggest that folate fortification has led to reduction in incidence of certain childhood cancers such as neuroblastoma, wilms tumour and leukaemias. Despite studies showing folate depletion during antifolate chemotherapy and higher toxicity of chemotherapy in folate-depleted individuals, folate supplementation during cancer chemotherapy is not routinely recommended. Studies investigating the precise effect of folate supplementation during chemotherapy on both short- and long-term outcomes of cancer are needed to arrive at a consensus guideline.

  8. 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.

  9. N-3 fatty acids, neuronal activity and energy metabolism in the brain

    Directory of Open Access Journals (Sweden)

    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  10. Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls.

    Science.gov (United States)

    Mochizuki, H; Oda, H; Yokogoshi, H

    2000-04-01

    The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.

  11. Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics

    Directory of Open Access Journals (Sweden)

    Carla Ferreri

    2016-12-01

    Full Text Available Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress—with an excess of radical and oxidative processes—cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1; and (ii the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects.

  12. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    International Nuclear Information System (INIS)

    Hingorani, V.; Brecher, P.

    1987-01-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6- 14 C]glucose or [1- 14 C]oleic acid and the incorporation of radioactivity into 14 CO 2 , lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO 2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14 CO 2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO 2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously

  13. Effects of supplementation with 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester on splanchnic amino acid metabolism and essential amino acid mobilization in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Dalbach, Kristine Foged; Larsen, Mogens; Raun, Birgitte Marie Løvendahl

    2011-01-01

    The present study aimed to investigate the effects of 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) supplementation on splanchnic AA metabolism, essential AA (EAA) mobilization, and plasma AA status in postpartum transition dairy cows. The EAA mobilization was calculated by differ......The present study aimed to investigate the effects of 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) supplementation on splanchnic AA metabolism, essential AA (EAA) mobilization, and plasma AA status in postpartum transition dairy cows. The EAA mobilization was calculated...

  14. Effects of competition on induction of crassulacean acid metabolism in a facultative CAM plant.

    Science.gov (United States)

    Yu, Kailiang; D'Odorico, Paolo; Li, Wei; He, Yongli

    2017-06-01

    Abiotic drivers of environmental stress have been found to induce CAM expression (nocturnal carboxylation) in facultative CAM species such as Mesembryanthemum crystallinum. The role played by biotic factors such as competition with non-CAM species in affecting CAM expression, however, remains largely understudied. This research investigated the effects of salt and water conditions on the competition between M. crystallinum and the C 3 grass Bromus mollis with which it is found to coexist in California's coastal grasslands. We also investigated the extent to which CAM expression in M. crystallinum was affected by the intensity of the competition with B. mollis. We found that M. crystallinum had a competitive advantage over B. mollis in drought and saline conditions, while B. mollis exerted strong competitive effects on M. crystallinum in access to light and soil nutrients in high water conditions. This strong competitive effect even outweighed the favorable effects of salt or water additions in increasing the biomass and productivity of M. crystallinum in mixture. Regardless of salt conditions, M. crystallinum did not switch to CAM photosynthesis in response to this strong competitive effect from B. mollis. Disturbance (i.e., grass cutting) reduced the competitive pressure by B. mollis and allowed for CAM expression in M. crystallinum when it was grown mixed with B. mollis. We suggest that moderate competition with other functional groups can enhance CAM expression in M. crystallinum, thereby affecting its plasticity and ability to cope with biological stress.

  15. Identification of differentially expressed reproductive and metabolic proteins in the female abalone (Haliotis laevigata) gonad following artificial induction of spawning.

    Science.gov (United States)

    Mendoza-Porras, Omar; Botwright, Natasha A; Reverter, Antonio; Cook, Mathew T; Harris, James O; Wijffels, Gene; Colgrave, Michelle L

    2017-12-01

    Inefficient control of temperate abalone spawning prevents pair-wise breeding and production of abalone with highly marketable traits. Traditionally, abalone farmers have used a combination of UV irradiation and application of temperature gradients to the tank water to artificially induce spawning. Proteins are known to regulate crucial processes such as respiration, muscle contraction, feeding, growth and reproduction. Spawning as a pre-requisite of abalone reproduction is likely to be regulated, in part, by endogenous proteins. A first step in elucidating the mechanisms that regulate spawning is to identify which proteins are directly involved during spawning. The present study examined protein expression following traditional spawning induction in the Haliotis laevigata female. Gonads were collected from abalone in the following physiological states: (1) spawning; (2) post-spawning; and (3) failed-to-spawn. Differential protein abundance was initially assessed using two-dimensional difference in-gel electrophoresis coupled with mass spectrometry for protein identification. A number of reproductive proteins such as vitellogenin, vitelline envelope zona pellucida domain 29 and prohibitin, and metabolic proteins such as thioredoxin peroxidase, superoxide dismutase and heat shock proteins were identified. Differences in protein abundance levels between physiological states were further assessed using scheduled multiple reaction monitoring mass spectrometry. Positive associations were observed between the abundance of specific proteins, such as heat shock cognate 70 and peroxiredoxin 6, and the propensity or failure to spawn in abalone. These findings have contributed to better understand both the effects of oxidative and heat stress over abalone physiology and their influence on abalone spawning. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. 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.

  18. Metabolism of nonparticulate phosphorus in an acid bog lake

    International Nuclear Information System (INIS)

    Koenings, J.P.

    1977-01-01

    In North Gate Lake, an acid bog lake located on the northern Michigan-Wisconsin border, U.S.A., the algal nutrient inorganic phosphate (FRP) is not detectable by chemical means. Organic phosphorus (FUP) represents 100% of the detectable filterable phosphorus. The availability and cycling of this organic fraction are of considerable interest in regard to the primary productivity of this system. To clarify these relationships, the cycling of nonparticulate forms of phosphorus found in the epilimnion of this lake was studied

  19. Metabolism of nonparticulate phosphorus in an acid bog lake

    Energy Technology Data Exchange (ETDEWEB)

    Koenings, J. P.

    1977-01-01

    In North Gate Lake, an acid bog lake located on the northern Michigan-Wisconsin border, U.S.A., the algal nutrient inorganic phosphate (FRP) is not detectable by chemical means. Organic phosphorus (FUP) represents 100% of the detectable filterable phosphorus. The availability and cycling of this organic fraction are of considerable interest in regard to the primary productivity of this system. To clarify these relationships, the cycling of nonparticulate forms of phosphorus found in the epilimnion of this lake was studied.

  20. Focal Thalamic Degeneration from Ethanol and Thiamine Deficiency is Associated with Neuroimmune Gene Induction, Microglial Activation, and Lack of Monocarboxylic Acid Transporters

    Science.gov (United States)

    Qin, Liya; Crews, Fulton T

    2014-01-01

    Background Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL). Although TD alone can cause WE, the high incidence in alcoholism suggests that TD and ethanol (EtOH) interact. Methods Mice in control, TD, or EtOH groups alone or combined were studied after 5 or 10 days of treatment. THAL and entorhinal cortex (ENT) histochemistry and mRNA were assessed. Results Combined EtOH-TD treatment for 5 days (EtOH-TD5) showed activated microglia, proinflammatory gene induction and THAL neurodegeneration that was greater than that found with TD alone (TD5), whereas 10 days resulted in marked THAL degeneration and microglial-neuroimmune activation in both groups. In contrast, 10 days of TD did not cause ENT degeneration. Interestingly, in ENT, TD10 activated microglia and astrocytes more than EtOH-TD10. In THAL, multiple astrocytic markers were lost consistent with glial cell loss. TD blocks glucose metabolism more than acetate. Acetate derived from hepatic EtOH metabolism is transported by monocarboxylic acid transporters (MCT) into both neurons and astrocytes that use acetyl-CoA synthetase (AcCoAS) to generate cellular energy from acetate. MCT and AcCoAS expression in THAL is lower than ENT prompting the hypothesis that focal THAL degeneration is related to insufficient MCT and AcCoAS in THAL. To test this hypothesis, we administered glycerin triacetate (GTA) to increase blood acetate and found it protected the THAL from TD-induced degeneration. Conclusions Our findings suggest that EtOH potentiates TD-induced THAL degeneration through neuroimmune gene induction. The findings support the hypothesis that TD deficiency inhibits global glucose metabolism and that a reduced ability to process acetate for cellular energy results in THAL focal degeneration in alcoholics contributing to the high incidence of Wernicke-Korsakoff syndrome in alcoholism. PMID

  1. Energetic and metabolic transient response of Saccharomyces cerevisiae to benzoic acid.

    Science.gov (United States)

    Kresnowati, M T A P; van Winden, W A; van Gulik, W M; Heijnen, J J

    2008-11-01

    Saccharomyces cerevisiae is known to be able to adapt to the presence of the commonly used food preservative benzoic acid with a large energy expenditure. Some mechanisms for the adaptation process have been suggested, but its quantitative energetic and metabolic aspects have rarely been discussed. This study discusses use of the stimulus response approach to quantitatively study the energetic and metabolic aspects of the transient adaptation of S. cerevisiae to a shift in benzoic acid concentration, from 0 to 0.8 mM. The information obtained also serves as the basis for further utilization of benzoic acid as a tool for targeted perturbation of the energy system, which is important in studying the kinetics and regulation of central carbon metabolism in S. cerevisiae. Using this experimental set-up, we found significant fast-transient (< 3000 s) increases in O(2) consumption and CO(2) production rates, of approximately 50%, which reflect a high energy requirement for the adaptation process. We also found that with a longer exposure time to benzoic acid, S. cerevisiae decreases the cell membrane permeability for this weak acid by a factor of 10 and decreases the cell size to approximately 80% of the initial value. The intracellular metabolite profile in the new steady-state indicates increases in the glycolytic and tricarboxylic acid cycle fluxes, which are in agreement with the observed increases in specific glucose and O(2) uptake rates.

  2. Use of deuterated tyrosine and phenylalanine in the study of catecholamine and aromatic acid metabolism

    International Nuclear Information System (INIS)

    Curtius, H.C.; Redweik, U.; Steinmann, B.; Leimbacher, W.; Wegmann, H.

    1975-01-01

    Deuterated tyrosine and phenylalanine have been used for the study of their respective metabolism in patients with phenylketonuria (PKU) and in healthy persons. Urinary excretion of dopamine and its metabolites was studied by GC-MS after oral administration of deuterated L-tyrosine in 2 patients with PKU and in normal controls at low and high plasma phenylalanine levels. From these studies it seemed that the in vivo tyrosine 3-hydroxylase activity and thus the formation of L-dopa depend on the phenylalanine concentration in plasma and also in tissues. After loading 3 mentally retarded patients with 3,5-[ 2 H 2 ]-4-hydroxyphenylalanine, we found, among others, excretion of deuterated m-hydroxyphenyl-hydracrylic acid, p-hydroxymandelic acid, p-hydroxybenzoic acid, p-hydroxyhippuric acid, benzoic acid and hippuric acid. An intramolecular rearrangement is postulated. Deuterated phenylalanine was used to investigate phenylalanine and dopa metabolism in PKU. In addition, one untreated person with PKU of normal intelligence and normal excretion of catecholamines at high plasma phenylalanine concentration was investigated in order to see whether there exists an alternative metabolic pathway from phenylalanine to dopa formation

  3. Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

    Science.gov (United States)

    Panchal, Sunil K; Ward, Leigh; Brown, Lindsay

    2013-03-01

    Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome. Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised. High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1. Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

  4. 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.

  5. 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

  6. Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic-co-glycolic acid), and Silica Nanoparticles.

    Science.gov (United States)

    Saborano, Raquel; Wongpinyochit, Thidarat; Totten, John D; Johnston, Blair F; Seib, F Philipp; Duarte, Iola F

    2017-07-01

    Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications. 1 H NMR analysis of cell extracts and culture media is used to quantify the changes in the intracellular and extracellular metabolomes of macrophages in response to nanoparticle exposure. Increased glycolytic activity, an altered tricarboxylic acid cycle, and reduced ATP generation are consistent with a proinflammatory phenotype. Furthermore, amino acids possibly arising from autophagy, the creatine kinase/phosphocreatine system, and a few osmolytes and antioxidants emerge as important players in the metabolic reprogramming of macrophages exposed to nanoparticles. This metabolic signature is a common response to all nanoparticles tested; however, the direction and magnitude of some variations are clearly nanoparticle specific, indicating material-induced biological specificity. Overall, metabolic reprogramming of macrophages can be achieved with nanoparticle treatments, modulated through the choice of the material, and monitored using 1 H NMR metabolomics. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM.

    Science.gov (United States)

    Yu, J; Wu, H; Lin, Z; Su, K; Zhang, J; Sun, F; Wang, X; Wen, C; Cao, H; Hu, L

    2017-12-01

    Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg -1 SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography-mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

  8. Physiological and metabolic effects of 5-aminolevulinic acid for mitigating salinity stress in creeping bentgrass.

    Directory of Open Access Journals (Sweden)

    Zhimin Yang

    Full Text Available The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA, could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera, was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L-1 weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid, amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid, and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose. ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense.

  9. Study of metabolism of hydrazoic acid in the purex process

    International Nuclear Information System (INIS)

    Violet, A.

    1988-03-01

    The transfer of HN 3 between different phases has been studied - It has been found that the transfer of HN 3 from aqueous solution of the reprocessing to gaz phase is a physical mechanism of desorbtion. - The limiting phenomena of the transfer of HN 3 fromt the organic to the gaseous phase, is the decomplexation of this specy with tributyl phosphate (TBP). - Chemical reactions of hydrazoic acid occurring with nitrogen oxides in the gaseous flow has shown that it is rapidly destroyed in the presence of nitrogen dioxide [fr

  10. 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.

  11. An accurate description of Aspergillus niger organic acid batch fermentation through dynamic metabolic modelling.

    Science.gov (United States)

    Upton, Daniel J; McQueen-Mason, Simon J; Wood, A Jamie

    2017-01-01

    Aspergillus niger fermentation has provided the chief source of industrial citric acid for over 50 years. Traditional strain development of this organism was achieved through random mutagenesis, but advances in genomics have enabled the development of genome-scale metabolic modelling that can be used to make predictive improvements in fermentation performance. The parent citric acid-producing strain of A. niger , ATCC 1015, has been described previously by a genome-scale metabolic model that encapsulates its response to ambient pH. Here, we report the development of a novel double optimisation modelling approach that generates time-dependent citric acid fermentation using dynamic flux balance analysis. The output from this model shows a good match with empirical fermentation data. Our studies suggest that citric acid production commences upon a switch to phosphate-limited growth and this is validated by fitting to empirical data, which confirms the diauxic growth behaviour and the role of phosphate storage as polyphosphate. The calibrated time-course model reflects observed metabolic events and generates reliable in silico data for industrially relevant fermentative time series, and for the behaviour of engineered strains suggesting that our approach can be used as a powerful tool for predictive metabolic engineering.

  12. Fatty acid metabolism and deposition in subcutaneous adipose tissue of pasture and feedlot finished cattle

    Science.gov (United States)

    An experiment was conducted to evaluate the effects of pasture finishing versus high-concentrate finishing, over time, on fatty acid metabolism in Angus crossbred (n = 24) steers. Ruminal fluid, serum, and adipose tissue biopsies were obtained on d 0, 28, 84, and 140. Pasture forages and diet ingr...

  13. Metabolic syndrome in patients with morbid obesity, according to different levels of serum uric acid.

    OpenAIRE

    Hordonho, Ana Adélia Cavalcante

    2009-01-01

    Although uric acid has a character antioxidant, when in increased serum levels, has been associated in several studies with various pathological conditions, particularly with obesity, cardiovascular disease, diabetes mellitus, dyslipidemia, hyperinsulinemia and insulin resistance, this being identified as the primary change of the metabolic syndrome. However, these studies were not performed on samples formed specifically for morbid obeses, where hyperuricemia is a common findi...

  14. Metabolic Disruption Early in Life is Associated With Latent Carcinogenic Activity of Dichloroacetic Acid in Mice

    Science.gov (United States)

    Early-life environmental factors can influence later-life susceptibility to cancer. Recent evidence suggests that metabolic pathways may mediate this type of latency effect. Previously, we reported that short-term exposure to dichloroacetic acid (DCA) increased liver cancer in mi...

  15. Metabolic Interaction between Urea Cycle and Citric Acid Cycle Shunt: A Guided Approach

    Science.gov (United States)

    Pesi, Rossana; Balestri, Francesco; Ipata, Piero L.

    2018-01-01

    This article is a guided pedagogical approach, devoted to postgraduate students specializing in biochemistry, aimed at presenting all single reactions and overall equations leading to the metabolic interaction between ureagenesis and citric acid cycle to be incorporated into a two-three lecture series about the interaction of urea cycle with other…

  16. Effect of folic acid on methionine and homocysteine metabolism in end-stage renal disease

    NARCIS (Netherlands)

    Stam, F.; van Guldener, C.; ter Wee, P.M.; Jakobs, C.A.J.M.; van der Meer, K.; Stehouwer, C.D.A.

    2005-01-01

    Background. The pathogenesis of hyperhomocysteinemia in end-stage renal disease (ESRD) is unclear. Folic acid lowers, but does not normalize, the plasma homocysteine level in patients with ESRD, but its effect on whole body metabolism of homocysteine is unknown. Methods We studied the effect of 3

  17. Effect of acute metabolic acid/base shifts on the human airway calibre.

    NARCIS (Netherlands)

    Brijker, F.; Elshout, F.J.J. van den; Heijdra, Y.F.; Bosch, F.H.; Folgering, H.T.M.

    2001-01-01

    Acute metabolic alkalosis (NaHCO(3)), acidosis (NH(4)Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24-56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid-base shifts were determined

  18. EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE

    Science.gov (United States)

    EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSEM F Hughes1, V Devesa2, B C Edwards1, C T Mitchell1, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hill, NCMonomethylar...

  19. Cardiac metabolism of 15 (p-I-123 phenyl-) pentadecanoic acid after intracoronary tracer application

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Reichmann, K.; Knopp, R.; Winkler, C.; Koischwitz, D.; Machulla, H.J.; Simon, H.

    1984-05-01

    Myocardial turnover of ..omega..-(p/sup 123/I-Phenyl-) pentadecanoic acid and release of its metabolites into the coronary sinus and peripheral blood has been studied in patients with coronary artery and valvular heart disease. After intracoronary tracer injection myocardial extraction fractions of 45-53% in control subjects were observed. In patients with coronary artery disease (CAD) normal to reduced values (34-61%) were established. Hydrophilic catabolites of I-PPA, probably p/sup 123/I-benzoic and -hippuric acid as well as small amounts of the non-metabolized tracer were found in coronary sinus and peripheral blood. Myocardial tracer uptake and clearance patterns were clearly different in normal myocardium when compared to that obtained in patients with CAD. Thus, evaluation of myocardial I-PPA metabolism might provide a new diagnostic tool for assessment of integrity of the heart's muscular metabolic function.

  20. The metabolism of phytanic acid and pristanic acid in man: a review

    NARCIS (Netherlands)

    Verhoeven, N. M.; Wanders, R. J.; Poll-The, B. T.; Saudubray, J. M.; Jakobs, C.

    1998-01-01

    The branched-chain fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this fatty acid in the human body is preceded by activation to phytanoyl-CoA and starts with one cycle of alpha-oxidation. Intermediates in this pathway are

  1. The role of adipose tissue and excess of fatty acids in the induction of insulin resistance in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Agnieszka Błachnio-Zabielska

    2016-11-01

    Full Text Available Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes and type 2 diabetes (T2D. The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA, diacylglycerols (DAG and ceramides (Cer. It has been demonstrated that accumulation of each of the above-mentioned lipid classes negatively affects the insulin signaling pathway. It is not clear which of those lipids play the most important role in HFD-induced skeletal muscle IRes. The aim of the present work is to present the current knowledge of the role of adipose tissue and excess of fatty acids in the induction of insulin resistance.

  2. Changes in the isozymic pattern of phosphoenolpyruvate : An early step in photoperiodic control of crassulacean acid metabolism level.

    Science.gov (United States)

    Brulfert, J; Arrabaça, M C; Guerrier, D; Queiroz, O

    1979-01-01

    Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one of the forms prevails under long-day treatment (low crassulacean acid metabolism level), the other develops under short-day treatment (high Crassulacean acid metabolism level). Molecular weights are significantly different: 175·10(3) and 186·10(3), respectively. These results indicate that two populations of phosphoenolyruvate carboxylase are present in the plant, one of which is responsible for Crassulacean acid metabolism activity under the control of photoperiod.The Crassulacean acid metabolism appears to depend on the same endogenous clock that governs other photoperiodically controlled events (e.g. flowering). The metabolic and energetic significance of this feature is discussed. It is suggested that modification in isozymic composition could be an early step in the response to photoperiodism at the metabolic level.

  3. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    Directory of Open Access Journals (Sweden)

    Shengxi Meng

    2013-01-01

    Full Text Available Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA, one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.

  4. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana

    2014-01-01

    .i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...... (pinsulin sensitivity (p... of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid...

  5. Radioiodinated PHIPA`s; metabolically trapped fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhut, M. [Heidelberg Univ. (Germany). Radiopharmaceutical Chemistry Lab.

    1998-12-31

    Radioiodinated PHIPA 3-10 [13-(4`-iodophenyl)-3-(p-phenylene)tridecanoic acid] has been developed for nuclear-cardiological investigation of coronary artery disease or cardiomyopathies of various origin. The compound features a phenylene group located within the backbone of a long-chain fatty acid. In spite of its bulky structure [{sup 123}I]PHIPA 3-10 is extracted by the myocardium in a manner similar to that for the unmodified fatty acid analogue, [{sup 123}I]IPPA. The retention of PHIPA 3-10 in heart muscle results from the presence of the p-phenylene group which prevents more than one {beta}-oxidation cycle. Only one single, rapidly formed metabolite was found in rat-heart extracts. According to comparative HPLC with synthetic metabolites and mass spectrometric analysis this metabolite was identified as [{sup 123}I]PHIPA 1-10, a by two methylene groups shortened PHIPA derivative. Formation of this metabolite could be suppressed by Etomoxir, a carnitine palmitoyl fransferase I inhibitor, indicating {beta}-oxidation of [{sup 123}I]PHIPA 3-10 in mitochondria. Final evidence for the involvement of mitochondria in the degradation of [{sup 123}I]PHIPA 3-10 was obtained performing density-gradient centrifugation with homogenized rat heart tissue. Labeled free PHIPA 3-10 and free metabolite peaked with the fraction containing mitochondria. With respect to its biochemical characteristics, [{sup 123}I]PHIPA 3-10 may be considered as a useful tool for nuclear cardiological investigations. (orig.) [Deutsch] Radioiodierte PHIPA 3-10 [13-(4`-Iodophenyl)-3-(p-phenylene)tridecanoic acid] wurde fuer Untersuchungen von koronaren Herzerkrankungen und Kardiomyopathien unterschiedlicher Genese entwickelt. Die Verbindung enthaelt eine in der Fettsaeurekette lokalisierte Phenylengruppe. Obwohl dieses Strukturelement raumfordernd ist, wird [{sup 123}I]PHIPA 3-10 aehnlich gut vom Herzmuskel aufgenommen, wie die unmodifizierte Fettsaeure [{sup 123}I]IPPA. Die auffallende

  6. The association between concentration of Uric Acid and metabolic syndrome among adolescents

    Directory of Open Access Journals (Sweden)

    Homeira Rashidi

    2015-11-01

    Full Text Available Background: Metabolic syndromes are known as a set of risk factors for the development of cardio-vascular disease and diabetes in the individual. The association between concentration of uric acid and metabolic syndrome in adolescents has yet to be established thoroughly. The aim of this study was to investigate the relationship between uric acid and metabolic syndrome in a sample of adolescents. Methods: This cross-sectional study was conducted from September 23, 2009 to September 22, 2010 in Jundishapur University of Medical Sciences, Ahvaz, Iran. In this study, 240 individuals aged 10-19 years were randomly selected among participants of the Ahvaz MetS study (120 subjects normal and 120 subjects MetS. The serum levels of UA were measured by a colorimetric method. In the normal group, anyone with abdominal obesity, high systolic or diastolic blood pressure, High-density lipoprotein (HDL≤40 mg/dl, TG≤110 mg/dl, fasting blood sugar (FBS≤100 mg/dl or diabetes was excluded from the study. History of Anticonvulsive drugs or steroids use was the criteria for exclusion for both groups. Results: Of the 240 subjects aged a mean of 14.95±2.64 years, mean of uric acid in metabolic syndrome group was 4.8±1.4 mg/dl and in the control group was 4.18±1.01 mg/d (P=0.001. Participants were divided into three groups based on uric acid levels: ≤4.9 mg/dl, 4.9-5.7 mg/dl and >5.7 mg/dl. The risk of metabolic syndrome was significantly higher in third group of uric acid than the second and first group (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.70 - 8.04 and (OR, 5.9; 95% CI, 2.42-14.35, P<0.001. In addition, uric acid level was inversely associated with hyperglycemia. The ORs of hypertriglyceridemia for the second and third group of uric acid were 4.36 (95% CI, 2.01- 9.47 5.75 (95% CI, 2.43-13.61 respectively, compared with lowest group of UA. Conclusion: The results showed that hyperuricemia was significantly linked with increased risk for

  7. Short-Chain Fatty Acids Enhance the Lipid Accumulation of 3T3-L1 Cells by Modulating the Expression of Enzymes of Fatty Acid Metabolism.

    Science.gov (United States)

    Yu, Haining; Li, Ran; Huang, Haiyong; Yao, Ru; Shen, Shengrong

    2018-01-01

    Short-chain fatty acids (SCFA) such as acetic acid, propionic acid, and butyric acid are produced by fermentation by gut microbiota. In this paper, we investigate the effects of SCFA on 3T3-L1 cells and the underlying molecular mechanisms. The cells were treated with acetic acid, propionic acid, or butyric acid when cells were induced to differentiate into adipocytes. MTT assay was employed to detect the viability of 3T3-L1 cells. Oil Red O staining was used to visualize the lipid content in 3T3-L1 cells. A triglyceride assay kit was used to detect the triacylglycerol content in 3T3-L1 cells. qRT-PCR and Western blot were used to evaluate the expression of metabolic enzymes. MTT results showed that safe concentrations of acetic acid, propionic acid, and butyric acid were less than 6.4, 3.2, and 0.8 mM, respectively. Oil Red O staining and triacylglycerols detection results showed that treatment with acetic acid, propionic acid, and butyric acid accelerated the 3T3-L1 adipocyte differentiation. qRT-PCR and Western blot results showed that the expressions of lipoprotein lipase (LPL), adipocyte fatty acid binding protein 4 (FABP4), fatty acid transporter protein 4 (FATP4), and fatty acid synthase (FAS) were significantly increased by acetic acid, propionic acid, and butyric acid treatment during adipose differentiation (p fatty acid metabolism. © 2018 AOCS.

  8. Effect of Non-Esterified Fatty Acids on Fatty Acid Metabolism-Related Genes in Calf Hepatocytes Cultured in Vitro

    Directory of Open Access Journals (Sweden)

    Peng Li

    2013-11-01

    Full Text Available Background: NEFA plays numerous roles in the metabolism of glucose, lipids, and proteins. A number of experimental studies have shown that NEFA may have an important role in fatty acid metabolism in the liver, especially in dairy cows that experience negative energy balance (NEB during early lactation. Methods: In this study, using fluorescent quantitative RT-PCR, ELISA, and primary hepatocytes cultured in vitro, we examined the effect of NEFA (0, 0.2, 0.4, 0.8, 1.6, and 3.2 mmol/L on fatty acid metabolism by monitoring the mRNA and protein expression of the following key enzymes: long chain acyl-CoA synthetase (ACSL, carnitine palmitoyltransferase IA (CPT IA, long chain acyl-CoA dehydrogenase (ACADL, and acetyl-CoA carboxylase (ACC. Results: The mRNA and protein expression levels of ACSL and ACADL markedly increased as the concentration of NEFA in the media was increased. The mRNA and protein expression levels of CPT IA were enhanced significantly when the NEFA concentrations increased from 0 to 1.6 mmol/L and decreased significantly when the NEFA concentrations increased from 1.6 to 3.2 mmol/L. The mRNA and protein expression of ACC decreased gradually with increasing concentrations of NEFA. Conclusion: These findings indicate that increased NEFA significantly promote the activation and β-oxidation of fatty acids, but very high NEFA concentrations may inhibit the translocation of fatty acids into mitochondria of hepatocytes. This may explain the development of ketosis or liver lipidosis in dairy cows. CPT IA might be the key control enzyme of the fatty acid oxidation process in hepatocytes.

  9. Hyperlipidaemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Koopmans, S.J.; Jong, M.C.; Que, I.; Dahlmans, V.E.H.; Pijl, H.; Radder, J.K.; Frölich, M.; Havekes, L.M.

    2001-01-01

    Aims/hypothesis. Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial

  10. Uric Acid Stimulates Fructokinase and Accelerates Fructose Metabolism in the Development of Fatty Liver

    Science.gov (United States)

    Lanaspa, Miguel A.; Sanchez-Lozada, Laura G.; Cicerchi, Christina; Li, Nanxing; Roncal-Jimenez, Carlos A.; Ishimoto, Takuji; Le, Myphuong; Garcia, Gabriela E.; Thomas, Jeffrey B.; Rivard, Christopher J.; Andres-Hernando, Ana; Hunter, Brandi; Schreiner, George; Rodriguez-Iturbe, Bernardo; Sautin, Yuri Y.; Johnson, Richard J.

    2012-01-01

    Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-phosphate; intracellular uric acid is also generated as a consequence of the transient ATP depletion that occurs during this reaction. Here we show in human hepatocytes that uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. Inhibition of uric acid production markedly blocked fructose-induced triglyceride accumulation in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates KHK expression involves the activation of the transcription factor ChREBP, which, in turn, results in the transcriptional activation of KHK by binding to a specific sequence within its promoter. Since subjects sensitive to fructose often develop phenotypes associated with hyperuricemia, uric acid may be an underlying factor in sensitizing hepatocytes to fructose metabolism during the development of fatty liver. PMID:23112875

  11. beta-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart.

    Science.gov (United States)

    DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J

    1989-01-01

    The use of 15-p-iodophenyl-beta-methyl-pentadecanoic acid (beta Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both beta Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, beta Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond beta Me-IPPA-CoA in the oxidative pathway.

  12. β-methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

    International Nuclear Information System (INIS)

    DeGrado, T.R.; Holden, J.E.; Ng, C.K.; Raffel, D.M.; Gatley, S.J.

    1989-01-01

    The use of 15-p-iodophenyl-β-methyl-pentadecanoic acid (βMe-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both βMe-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, βMe-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond βMe-IPPA-CoA in the oxidative pathway. (orig.)

  13. beta. -methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    DeGrado, T.R.; Holden, J.E.; Ng, C.K.; Raffel, D.M.; Gatley, S.J.

    1989-02-01

    The use of 15-p-iodophenyl-..beta..-methyl-pentadecanoic acid (..beta..Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both ..beta..Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2(5(4-chlorophenyl)pentyl)oxirane-2-carboxylate (POCA). In contrast, ..beta..Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond ..beta..Me-IPPA-CoA in the oxidative pathway.

  14. L-[4-11C]aspartic acid: enzymatic synthesis, myocardial uptake, and metabolism

    International Nuclear Information System (INIS)

    Barrio, J.R.; Egbert, J.E.; Henze, E.; Schelbert, H.R.; Baumgartner, F.J.

    1982-01-01

    Sterile, pyrogen-free L-[4- 11 C]aspartic acid was prepared from 11 CO 2 using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-[4- 11 C]aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of 11 CO 2 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of 11 CO 2 . Positron-computed tomography imaging showed that the 11 C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-[4- 11 C]aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-[4- 11 C]aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism

  15. The metabolism of tritiated oleic acid in the rat. A radiological protection study

    International Nuclear Information System (INIS)

    Jeanmaire, Lucien; Vernois, Yvette; Nazard, Raymonde.

    1979-04-01

    The metabolism of 3 H-labelled oleic acid has been studied in the rat during 600 days. The results of urinary and fecal excretions, of the retention of the total and fixed activities in 25 tissues or organs and the cumulative activity from day 4 to 616 are discussed. Oleic acid is more widely spread than other labelled molecules studied previously both as regard excretion or retention. During the first 4 days one can grossly admit that half the activity is fixed to water and half is stored in the adipose tissues which it leaves quickly first, then more slowly with a half-life of 200 days about. For some ten tissues, the cumulative activity due to the fixed fraction exceeds the cumulative activity due to tritiated water obtained by metabolism of oleic acid [fr

  16. Metabolic labeling of sialic acids in tissue culture cell lines: methods to identify substituted and modified radioactive neuraminic acids

    International Nuclear Information System (INIS)

    Diaz, S.; Varki, A.

    1985-01-01

    The parent sialic acid N-acetylneuraminic acid can be modified or substituted in various ways, giving rise to a family of more than 25 compounds. The definitive identification of these compounds has previously required isolation of nanomole amounts for mass spectrometry or NMR. We have explored the possibility of using the known metabolic precursors of the sialic acids, particularly N-acetyl-[6-3H]mannosamine, to label and identify various forms of sialic acids in tissue culture cells. Firstly, we defined several variables that affect the labeling of sialic acids with N-acetyl-[6-3H]mannosamine. Secondly, we have devised a simple screening method to identify cell lines that synthesize substituted or modified sialic acids. We next demonstrate that it is possible to definitively identify the natures of the various labeled sialic acids without the use of mass spectrometry, even though they are present only in tracer amounts. The methods used include paper chromatography, analytical de-O-acetylation, periodate release of the 9-3H as [3H]formaldehyde (which is subsequently converted to a specific 3H-labeled chromophore), acylneuraminate pyruvate lyase treatment with identification of [3H]acylmannosamines, gas-liquid chromatography with radioactive detection, and two new high-pressure liquid chromatography methods utilizing the amine-adsorption:ion suppression and ion-pair principles. The use of an internal N-acetyl-[4-14C]neuraminic acid standard in each of these methods assures precision and accuracy. The combined use of these methods now allows the identification of radioactive tracer amounts of the various types of sialic acids in well-defined populations of tissue culture cells; it may also allow the identification of hitherto unknown forms of sialic acids

  17. Eicosapentaenoic acid in cancer improves body composition and modulates metabolism.

    Science.gov (United States)

    Pappalardo, Giulia; Almeida, Ana; Ravasco, Paula

    2015-04-01

    The objective of this review article is to present the most recent intervention studies with EPA on nutritional outcomes in cancer patients, e.g. nutritional status, weight & lean body mass. For this purpose a PubMed(®) and MedLine(®) search of the published literature up to and including January 2014 that contained the keywords: cancer, sarcopenia, EPA, ω-3 fatty acids, weight, intervention trial, muscle mass was conducted. The collected data was summarized and written in text format and in tables that contained: study design, patient' population, sample size, statistical significance and results of the intervention. The paper will cover malignancy, body composition, intervention with EPA, physiological mechanisms of action of EPA, effect of EPA on weight and body composition, future research. In cancer patients deterioration of muscle mass can be present regardless of body weight or Body Mass Index (BMI). Thus, sarcopenia in cancer patients with excessive fat mass (FM), entitled sarcopenic obesity, has gained greater relevance in clinical practice; it can negatively influence patients' functional status, tolerance to treatments & disease prognosis. The search for an effective nutritional intervention that improves body composition (preservation of muscle mass and muscle quality) is of utmost importance for clinicians and patients. The improvement of muscle quality is an even more recent area of interest because it has probable implications in patients' prognosis. Eicosapentaenoic acid (EPA) has been identified as a promising nutrient with the wide clinical benefits. Several mechanisms have been proposed to explain EPA potential benefits on body composition: inhibition of catabolic stimuli by modulating pro-inflammatory cytokines production and enhancing insulin sensitivity that induces protein synthesis; also, EPA may attenuate deterioration of nutritional status resulting from antineoplastic therapies by improving calorie and protein intake as well. Indeed

  18. Lysophosphatidic acid metabolism and elimination in cardiovascular disease

    Science.gov (United States)

    Salous, Abdelghaffar Kamal

    The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are present in human and mouse plasma at a concentration of ~0.1-1 microM and regulate physiological and pathophysiological processes in the cardiovascular system including atherothrombosis, intimal hyperplasia, and immune function, edema formation, and permeability. PPAP2B, the gene encoding LPP3, a broad activity integral membrane enzyme that terminates LPA actions in the vasculature, has a single nucleotide polymorphism that been recently associated with coronary artery disease risk. The synthesis and signaling of LPA and S1P in the cardiovascular system have been extensively studied but the mechanisms responsible for their elimination are less well understood. The broad goal of this research was to examine the role of LPP3 in the termination of LPA signaling in models of cardiovascular disease involving vascular wall cells, investigate the role of LPP3 in the elimination of plasma LPA, and further characterize the elimination of plasma LPA. The central hypothesis is that LPP3 plays an important role in attenuating the pathological responses to LPA signaling and that it mediates the elimination of exogenously applied bioactive lipids from the plasma. These hypotheses were tested using molecular biological approaches, in vitro studies, synthetic lysophospholipid mimetics, modified surgical procedures, and mass spectrometry assays. My results indicated that LPP3 played a critical role in attenuating LPA signaling mediating the pathological processes of intimal hyperplasia and vascular leak in mouse models of disease. Additionally, enzymatic inactivation of lysophospholipids by LPP and PLA enzymes in the plasma was not a primary mechanism for the rapid elimination of plasma LPA and S1P. Instead, evidence strongly suggested a transcellular uptake mechanism by hepatic non-parenchymal cells as the predominant mechanism for elimination of these molecules. These results support a model in

  19. Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPARα-Dependent AMPK Activation.

    Science.gov (United States)

    de Souza, Camila O; Teixeira, Alexandre A S; Biondo, Luana A; Lima Junior, Edson A; Batatinha, Helena A P; Rosa Neto, Jose C

    2017-08-01

    Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. C57BL6 and PPARα knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPARα. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPARα KO mice. In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPARα. J. Cell. Physiol. 232: 2168-2177, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Induction of amino acid transporters expression by endurance exercise in rat skeletal muscle

    International Nuclear Information System (INIS)

    Murakami, Taro; Yoshinaga, Mariko

    2013-01-01

    Highlights: •Regulation of amino acid transporter expression in working muscle remains unclear. •Expression of amino acid transporters for leucine were induced by a bout of exercise. •Requirement of leucine in muscle cells might regulate expression of its transporters. •This information is beneficial for understanding the muscle remodeling by exercise. -- Abstract: We here investigated whether an acute bout of endurance exercise would induce the expression of amino acid transporters that regulate leucine transport across plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we observed that expression of mRNAs encoding L-type amino acid transporter 1 (LAT1) and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was also induced by the exercise in those three muscles. Expression of proton-assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced mRNA expression of these amino acid transporters appeared to be attenuated by repeated bouts of the exercise. These results suggested that the expression of amino acid transporters for leucine may be induced in response to an increase in the requirement for this amino acid in the cells of working skeletal muscles

  1. /sup 1/H-NMR urinalysis. Simultaneous screening of inborn errors of metabolism of amino acid and organic acid disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Hideaki; Yamaguchi, Shuichi

    1988-02-01

    In an effort to examine the usefulness of /sup 1/H-nuclear magnetic resonance (NMR) urinalysis in the diagnosis of congenital metabolic disorders, 70 kinds of urinary metabolites were analysed in relation to the diagnosis of inborn errors of amino acid and organic acid disorders. Homogated decoupling (HMG) method failed to analyze six metabolites within the undetectable range. When non-decoupling method (NON), in which the materials are dissolved in dimethyl sulfoxide, was used, the identification of signals became possible. The combination of HMG and NON methods was, therefore, considered to identify all of the metabolites. When the urine samples, which were obtained from patients with hyperglycerolemia, hyperornithinemia, glutaric acidemia type II, or glycerol kinase deficiency, were analysed by using both HMG and NON methods, abnormally increased urinary metabolites were detected. /sup 1/H-NMR urinalysis, if used in the combination of HMG and NON methods, may allow simultanenous screening of inborn errors of metabolism of amino acid and organic acid disorders. (Namekawa, K.).

  2. Metabolic regulation of the plant hormone indole-3-acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Jerry D. Cohen

    2009-11-01

    The phytohormone indole-3-acetic acid (IAA, auxin) is important for many aspects of plant growth, development and responses to the environment yet the routes to is biosynthesis and mechanisms for regulation of IAA levels remain important research questions. A critical issue concerning the biosynthesis if IAA in plants is that redundant pathways for IAA biosynthesis exist in plants. We showed that these redundant pathways and their relative contribution to net IAA production are under both developmental and environmental control. We worked on three fundamental problems related to how plants get their IAA: 1) An in vitro biochemical approach was used to define the tryptophan dependent pathway to IAA using maize endosperm, where relatively large amounts of IAA are produced over a short developmental period. Both a stable isotope dilution and a protein MS approach were used to identify intermediates and enzymes in the reactions. 2) We developed an in vitro system for analysis of tryptophan-independent IAA biosynthesis in maize seedlings and we used a metabolite profiling approach to isolate intermediates in this reaction. 3) Arabidopsis contains a small family of genes that encode potential indolepyruvate decarboxylase enzymes. We cloned these genes and studied plants that are mutant in these genes and that over-express each member in the family in terms of the level and route of IAA biosynthesis. Together, these allowed further development of a comprehensive picture of the pathways and regulatory components that are involved in IAA homeostasis in higher plants.

  3. Ascorbic acid (AA) metabolism in protection against radiation damage

    International Nuclear Information System (INIS)

    Rose, R.C.; Koch, M.J.

    1986-01-01

    The possibility is considered that AA protects tissues against radiation damage by scavenging free radicals that result from radiolysis of water. A physiologic buffer (pH 6.7) was incubated with 14 C-AA and 1 mM thiourea (to slow spontaneous oxidation of AA). Aliquots were assayed by HPLC and scintillation spectrometry to identify the 14 C-label. Samples exposed to Cobalt-60 radiation had a half time of AA decay of 30 minutes) indicating that AA scavenges radiation-induced free radicals and forms the ascorbate free radical (AFR). Pairs of 14 C-AFR disproportionate, with the net effect of 14 C-dehydroascorbic acid formation from 14 C-AA. Having established that AFR result from ionizing radiation in an aqueous solution, the possibility was evaluated that a tissue factor reduces AFR. Cortical tissue from the kidneys of male rats was minced, homogenized in buffer and centrifuged at 8000 xg. The supernatant was found to slow the rate of radiation-induced AA degradation by > 90% when incubated at 23 0 C in the presence of 15 μM 14 C-AA. Samples of supernatant maintained at 100 0 C for 10 minutes or precipitated with 5% PCA did not prevent radiation-induced AA degradation. AA may have a specific role in scavenging free radicals generated by ionizing radiation and thereby protect body tissues

  4. Fatty acid metabolism, energy expenditure and insulin resistance in muscle.

    Science.gov (United States)

    Turner, Nigel; Cooney, Gregory J; Kraegen, Edward W; Bruce, Clinton R

    2014-02-01

    Fatty acids (FAs) are essential elements of all cells and have significant roles as energy substrates, components of cellular structure and signalling molecules. The storage of excess energy intake as fat in adipose tissue is an evolutionary advantage aimed at protecting against starvation, but in much of today's world, humans are faced with an unlimited availability of food, and the excessive accumulation of fat is now a major risk for human health, especially the development of type 2 diabetes (T2D). Since the first recognition of the association between fat accumulation, reduced insulin action and increased risk of T2D, several mechanisms have been proposed to link excess FA availability to reduced insulin action, with some of them being competing or contradictory. This review summarises the evidence for these mechanisms in the context of excess dietary FAs generating insulin resistance in muscle, the major tissue involved in insulin-stimulated disposal of blood glucose. It also outlines potential problems with models and measurements that may hinder as well as help improve our understanding of the links between FAs and insulin action.

  5. Producing Acetic Acid of Acetobacter pasteurianus by Fermentation Characteristics and Metabolic Flux Analysis.

    Science.gov (United States)

    Wu, Xuefeng; Yao, Hongli; Liu, Qing; Zheng, Zhi; Cao, Lili; Mu, Dongdong; Wang, Hualin; Jiang, Shaotong; Li, Xingjiang

    2018-03-19

    The acetic acid bacterium Acetobacter pasteurianus plays an important role in acetic acid fermentation, which involves oxidation of ethanol to acetic acid through the ethanol respiratory chain under specific conditions. In order to obtain more suitable bacteria for the acetic acid industry, A. pasteurianus JST-S screened in this laboratory was compared with A. pasteurianus CICC 20001, a current industrial strain in China, to determine optimal fermentation parameters under different environmental stresses. The maximum total acid content of A. pasteurianus JST-S was 57.14 ± 1.09 g/L, whereas that of A. pasteurianus CICC 20001 reached 48.24 ± 1.15 g/L in a 15-L stir stank. Metabolic flux analysis was also performed to compare the reaction byproducts. Our findings revealed the potential value of the strain in improvement of industrial vinegar fermentation.

  6. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook; Kang, Keon Wook; Oh, Soo Jin; Lee, Ki Ho; Kim, Hwan Mook; Ma, Jin Yeul; Kim, Sang Kyum

    2011-01-01

    Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to ∼ 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research highlights: → MCF-7/Adr cells showed decreases in cellular GSH

  7. Non-spectral interferences due to the presence of sulfuric acid in inductively coupled plasma mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    García-Poyo, M. Carmen; Grindlay, Guillermo; Gras, Luis [Department of Analytical Chemistry, Nutrition and Food Sciences, University of Alicante, P.O. Box 99, 03080 – Alicante (Spain); Loos-Vollebregt, Margaretha T.C. de, E-mail: margaretha.deloos@ugent.be [Delft University of Technology, Faculty of Applied Sciences, Analytical Biotechnology, Julianalaan 67, 2628 BC Delft (Netherlands); Ghent University, Department of Analytical Chemistry, Krijgslaan 281 - S12, 9000 Ghent (Belgium); Mora, Juan, E-mail: juan.mora@ua.es [Department of Analytical Chemistry, Nutrition and Food Sciences, University of Alicante, P.O. Box 99, 03080 – Alicante (Spain)

    2015-03-01

    Results of a systematic study concerning non-spectral interferences from sulfuric acid containing matrices on a large number of elements in inductively coupled plasma–mass spectrometry (ICP-MS) are presented in this work. The signals obtained with sulfuric acid solutions of different concentrations (up to 5% w w{sup −1}) have been compared with the corresponding signals for a 1% w w{sup −1−} nitric acid solution at different experimental conditions (i.e., sample uptake rates, nebulizer gas flows and r.f. powers). The signals observed for {sup 128}Te{sup +}, {sup 78}Se{sup +} and {sup 75}As{sup +} were significantly higher when using sulfuric acid matrices (up to 2.2-fold for {sup 128}Te{sup +} and {sup 78}Se{sup +} and 1.8-fold for {sup 75}As{sup +} in the presence of 5 w w{sup -1} sulfuric acid) for the whole range of experimental conditions tested. This is in agreement with previously reported observations. The signal for {sup 31}P{sup +} is also higher (1.1-fold) in the presence of sulfuric acid. The signal enhancements for {sup 128}Te{sup +}, {sup 78}Se{sup +}, {sup 75}As{sup +} and {sup 31}P{sup +} are explained in relation to an increase in the analyte ion population as a result of charge transfer reactions involving S{sup +} species in the plasma. Theoretical data suggest that Os, Sb, Pt, Ir, Zn and Hg could also be involved in sulfur-based charge transfer reactions, but no experimental evidence has been found. The presence of sulfuric acid gives rise to lower ion signals (about 10–20% lower) for the other nuclides tested, thus indicating the negative matrix effect caused by changes in the amount of analyte loading of the plasma. The elemental composition of a certified low-density polyethylene sample (ERM-EC681K) was determined by ICP-MS after two different sample digestion procedures, one of them including sulfuric acid. Element concentrations were in agreement with the certified values, irrespective of the acids used for the digestion. These

  8. Roles of renal ammonia metabolism other than in acid-base homeostasis.

    Science.gov (United States)

    Weiner, I David

    2017-06-01

    The importance of renal ammonia metabolism in acid-base homeostasis is well known. However, the effects of renal ammonia metabolism other than in acid-base homeostasis are not as widely recognized. First, ammonia differs from almost all other solutes in the urine in that it does not result from arterial delivery. Instead, ammonia is produced by the kidney, and only a portion of the ammonia produced is excreted in the urine, with the remainder returned to the systemic circulation through the renal veins. In normal individuals, systemic ammonia addition is metabolized efficiently by the liver, but in patients with either acute or chronic liver disease, conditions that increase the addition of ammonia of renal origin to the systemic circulation can result in precipitation and/or worsening of hyperammonemia. Second, ammonia appears to serve as an intrarenal paracrine signaling molecule. Hypokalemia increases proximal tubule ammonia production and secretion as well as reabsorption in the thick ascending limb of the loop of Henle, thereby increasing delivery to the renal interstitium and the collecting duct. In the collecting duct, ammonia decreases potassium secretion and stimulates potassium reabsorption, thereby decreasing urinary potassium excretion and enabling feedback correction of the initiating hypokalemia. Finally, the stimulation of renal ammonia metabolism by hypokalemia may contribute to the development of metabolic alkalosis, which in turn can stimulate NaCl reabsorption and contribute to the intravascular volume expansion, increased blood pressure and diuretic resistance that can develop with hypokalemia. The evidence supporting these novel non-acid-base roles of renal ammonia metabolism is discussed in this review.

  9. Effect of Ursolic Acid on Metabolic Syndrome, Insulin Sensitivity, and Inflammation.

    Science.gov (United States)

    Ramírez-Rodríguez, Alejandra M; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Acuña Ortega, Natalhie

    2017-09-01

    To evaluate the effect of ursolic acid on metabolic syndrome, insulin sensitivity, and inflammation, a randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (30-60 years) with a diagnosis of metabolic syndrome without treatment. They were randomly assigned to two groups of 12 patients, each to receive orally 150 mg of ursolic acid or homologated placebo once a day for 12 weeks. Before and after the intervention, the components of metabolic syndrome, insulin sensitivity (Matsuda index), and inflammation profile (interleukin-6 and C-reactive protein) were evaluated. After ursolic acid administration, the remission of metabolic syndrome occurred in 50% of patients (P = .005) with significant differences in body weight (75.7 ± 11.5 vs. 71 ± 11 kg, P = .002), body mass index (BMI) (29.9 + 3.6 vs. 24.9 ± 1.2 kg/m 2 , P = .049), waist circumference (93 ± 8.9 vs. 83 + 8.6 cm, P = .008), fasting glucose (6.0 ± 0.5 vs. 4.7 ± 0.4 mmol/L, P = .002), and insulin sensitivity (3.1 ± 1.1 vs. 4.2 ± 1.2, P = .003). Ursolic acid administration leads to transient remission of metabolic syndrome, reducing body weight, BMI, waist circumference and fasting glucose, as well as increasing insulin sensitivity.

  10. 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...

  11. Research progress in roles of gut microbiota and bile acid metabolism in development and progression of NAFLD

    Directory of Open Access Journals (Sweden)

    LU Xu

    2014-11-01

    Full Text Available With the prevalence of obesity and metabolic syndrome, the incidence of nonalcoholic fatty liver disease (NAFLD is increasing year by year. Studies have uncovered the important roles of gut microbiota and bile acid metabolism in the development and progression of NAFLD. The roles of gut microbiota, as well bile acid and bile acid receptors, in the development and progression of NAFLD are highlighted.

  12. Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

    Science.gov (United States)

    Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

    2016-06-01

    Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

  13. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Science.gov (United States)

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  14. Retinoic Acid-Related Orphan Receptors (RORs: Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Directory of Open Access Journals (Sweden)

    Donald N. Cook

    2015-12-01

    Full Text Available In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs. We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated.

  15. Metabolism of 15(p123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues

    International Nuclear Information System (INIS)

    Reske, S.N.; Sauer, W.; Winkler, C.; Machulla, H.J.; Knust, J.

    1985-01-01

    The uptake and turnover of W(p 123 I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3 H-oleic- or 14 C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues; dedpending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new γ-emitting isotope-labeled radiopharmaceutical. (orig.)

  16. Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State12

    Science.gov (United States)

    Adams, Sean H.

    2011-01-01

    Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). PMID:22332087

  17. Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

    Science.gov (United States)

    Shi, Bin; Wang, Li-Fang; Meng, Wen-Shu; Chen, Liang; Meng, Zi-Li

    2017-06-01

    Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide. In the present study, the possible benefits of carnosic acid combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3 signaling pathway was promoted in carnosic acid and fisetin co-treatment, which was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro-apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and fisetin combined treatment inhibited lung cancer growth in comparison to the carnosic acid or fisetin monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit lung cancer through caspase-3 activation.

  18. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

    1986-03-05

    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  19. Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.

    Science.gov (United States)

    Fuhrmeister, Jessica; Zota, Annika; Sijmonsma, Tjeerd P; Seibert, Oksana; Cıngır, Şahika; Schmidt, Kathrin; Vallon, Nicola; de Guia, Roldan M; Niopek, Katharina; Berriel Diaz, Mauricio; Maida, Adriano; Blüher, Matthias; Okun, Jürgen G; Herzig, Stephan; Rose, Adam J

    2016-06-01

    Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  20. Detailed predictive mapping of acid sulfate soil occurrence using electromagnetic induction data

    DEFF Research Database (Denmark)

    Beucher, Amélie; Boman, A; Mattbäck, S

    impact through the resulting corrosion of concrete and steel infrastructures, or their poor geotechnical qualities. Therefore, mapping acid sulfate soil occurrence constitutes a key step to target the strategic areas for subsequent environmental risk management and mitigation. Conventional mapping (i...... obtained from a EM38 proximal sensor enabled the refined mapping of acid sulfate soils over a field (Huang et al. 2014). The present study aims at developing an efficient and reliable method for the detailed predictive mapping of acid sulfate soil occurrence in a field located in western Finland. Different...

  1. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    Directory of Open Access Journals (Sweden)

    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  2. Gallic acid reduces cell growth by induction of apoptosis and reduction of IL-8 in HepG2 cells.

    Science.gov (United States)

    Lima, Kelly Goulart; Krause, Gabriele Catyana; Schuster, Aline Daniele; Catarina, Anderson Velasque; Basso, Bruno Souza; De Mesquita, Fernanda Cristina; Pedrazza, Leonardo; Marczak, Elisa Simon; Martha, Bianca Andrade; Nunes, Fernanda Bordignon; Chiela, Eduardo Cremonese Filippi; Jaeger, Natália; Thomé, Marcos Paulo; Haute, Gabriela Viegas; Dias, Henrique Bregolin; Donadio, Márcio Vinícius Fagundes; De Oliveira, Jarbas Rodrigues

    2016-12-01

    Hepatocellular carcinoma is the most prevalent primary liver tumor and is among the top ten cancer that affect the world population. Its development is related, in most cases, to the existence of chronic liver injury, such as in cirrhosis. The knowledge about the correlation between chronic inflammation and cancer has driven new researches with anti-inflammatory agents that have potential for the development of antitumor drugs. Gallic acid is a phenolic acid found in many natural products and have shown anti-inflammatory, anti-tumor, anti-mutagenic and antioxidant actions. The purpose of this study was to investigate the effect of gallic acid on acute and chronic cell proliferation and inflammatory parameters of hepatocellular carcinoma cells (HepG2), as well as to investigate the mechanisms involved. Results showed that the gallic acid decreased the proliferation of HepG2 cells in a dose-dependent manner (Trypan blue exclusion assay), without causing necrosis (LDH assay). We observed a significant increase in the percentage of small and regular nuclei (Nuclear Morphometric Analysis assay), a significant induction of apoptosis by Annexin V-FITC and PI assay and no interference with the cell cycle using the FITC BrdU Flow Kit. We observed a significant reduction in the levels of IL-8 and increased levels of IL-10 and IL-12 (Cytometric Bead Array Human Inflammation Assay). Furthermore, gallic acid caused no cancer cells regrowth at a long term (Cumulative Population Doubling assay). According to these results, gallic acid showed a strong potential as an anti-tumor agent in hepatocellular carcinoma cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Directory of Open Access Journals (Sweden)

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  4. Induction of the p75NTR by Aryl Propionic Acids in Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Quann, Emily

    2007-01-01

    .... I have found that treatment of prostate cancer cells with the aryl propionic acids R-flurbiprofen and ibuprofen induces reexpression of p75NTR, decreases cell survival, and increases apoptosis...

  5. Biochemical studies on the effect of fluoride on higher plants. I. Metabolism of carbohydrates, organic acids and amino acids. [Glycine max var. Hawkeye

    Energy Technology Data Exchange (ETDEWEB)

    Yang, S F; Miller, G W

    1963-01-01

    Metabolic processes associated with free sugars, organic acids and amino acids in higher plants subjected to fluoride fumigation were studied quantitatively. Fluoride-fumigated leaves contained more reducing sugars and less sucrose than the normal leaves. This result suggested inhibition of sucrose synthesis by fluoride. Necrotic leaves contained increased total concentrations of organic acids, which were mostly attributable to malic acid, malonic acid and citric acid. The greater increase in malic acid relative to that of citric acid was the reverse of results observed in chlorotic tissue. Necrotic leaves contained enhanced amounts of free amino acids. The greatest increase occurred in the concentration of asparagine and might be related to the increased respiratory rate of necrotic leaves. Pipecolic acid accumulated in large quantities in nicrotic tissue and was not detected in normal leaves. The accumulation of organic acids and amino acids in leaves during fluoride fumigation was evidenced by a lowered respiratory quotient.

  6. Effect of Bioprocessing on the In Vitro Colonic Microbial Metabolism of Phenolic Acids from Rye Bran Fortified Breads

    DEFF Research Database (Denmark)

    Koistinen, Ville M; Nordlund, Emilia; Katina, Kati

    2017-01-01

    in an in vitro colon model, the metabolites were analyzed using two different methods applying mass spectrometry. While phenolic acids were released more extensively from the bioprocessed bran bread and ferulic acid had consistently higher concentrations in the bread type during fermentation, there were only......Cereal bran is an important source of dietary fiber and bioactive compounds, such as phenolic acids. We aimed to study the phenolic acid metabolism of native and bioprocessed rye bran fortified refined wheat bread and to elucidate the microbial metabolic route of phenolic acids. After incubation...

  7. 2-Chloro-1,3-propanediol (2-MCPD) and its fatty acid esters: cytotoxicity, metabolism, and transport by human intestinal Caco-2 cells.

    Science.gov (United States)

    Buhrke, Thorsten; Frenzel, Falko; Kuhlmann, Jan; Lampen, Alfonso

    2015-12-01

    The food contaminants 3-chloro-1,2-propanediol (3-MCPD) and 3-MCPD fatty acid esters have attracted considerable attention in the past few years due to their toxic properties and their occurrence in numerous foods. Recently, significant amounts of the isomeric compounds 2-chloro-1,3-propanediol (2-MCPD) fatty acid esters have been detected in refined oils. Beside the interrogation which toxic effects might be related to the core compound 2-MCPD, the key question from the risk assessment perspective is again-as it was discussed for 3-MCPD fatty acid esters before-to which degree these esters are hydrolyzed in the gut, thereby releasing free 2-MCPD. Here, we show that free 2-MCPD but not 2-MCPD fatty acid esters were able to cross a monolayer of differentiated Caco-2 cells as an in vitro model for the human intestinal barrier. Instead, the esters were hydrolyzed by the cells, thereby releasing free 2-MCPD which was neither absorbed nor metabolized by the cells. Cytotoxicity assays revealed that free 2-MCPD as well as free 3-MCPD was not toxic to Caco-2 cells up to a level of 1 mM, whereas cellular viability was slightly decreased in the presence of a few 2-MCPD and 3-MCPD fatty acid esters at concentrations above 10 µM. The observed cytotoxic effects correlated well with the induction of caspase activity and might be attributed to the induction of apoptosis by free fatty acids which were released from the esters in the presence of Caco-2 cells.

  8. Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines

    International Nuclear Information System (INIS)

    Sasajima, Toshio; Miyagawa, Tadashi; Oku, Takamitsu; Gelovani, Juri G.; Finn, Ronald; Blasberg, Ronald

    2004-01-01

    Amino acid imaging is increasingly being used for assessment of brain tumor malignancy, extent of disease, and prognosis. This study explores the relationship between proliferative activity, amino acid transport, and glucose metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of growth in culture. Growth phase was characterized by direct cell counting, proliferation index determined by flow cytometry, and [ 3 H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([ 14 C]aminocyclopentane carboxylic acid (ACPC) and [ 14 C]aminoisobutyric acid (AIB)), and [ 18 F]fluorodeoxyglucose (FDG). Highly significant relationships between cell number (density), proliferation index, and TdR accumulation rate were observed in all cell lines (r>0.99). Influx (K 1 ) of both ACPC and AIB was directly related to cell density, and inversely related to the proliferation index and TdR accumulation in all cell lines. The volume of distribution (V d ) for ACPC and AIB was lowest during rapid growth and highest during the near-plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells was unaffected by proliferation rate, growth phase, and cell density, whereas FDG accumulation was correlated with TdR accumulation, growth phase, and cell density in U87 cells. This study demonstrates that proliferation rate and glucose metabolism are not necessarily co-related in all glioma cell lines. The values of K 1 and V d for ACPC and AIB under different growth conditions suggest that these tumor cell lines can up-regulate amino acid transporters in their cell membranes when their growth conditions become adverse and less than optimal. (orig.)

  9. Possible role for abscisic acid in regulation of photosynthetic and photorespiratory carbon metabolism in barley leaves

    International Nuclear Information System (INIS)

    Popova, L.P.; Tsonev, T.D.; Vaklinova, S.G.

    1987-01-01

    The influence of abscisic acid (ABA) on carbon metabolism, rate of photorespiration, and the activity of the photorespiratory enzymes ribulose bisphosphate oxygenase and glycolate oxidase in 7-day-old barley seedlings (Hordeum vulgare L. var. Alfa) was investigated. Plants treated with ABA had enhanced incorporation of labeled carbon from 14 CO 2 into glycolic acid, glycine, and serine, while 14 C incorporation into 3-phosphoglyceric acid and sugarphosphate esters was depressed. Parallel with this effect, treated plants showed a rise in activity of RuBP oxygenase and glycolic acid oxidase. The rate of photorespiration was increased twofold by ABA treatment at IO -6 molar while the CO 2 -compensation point increased 46% and stomatal resistance increased more than twofold over control plants

  10. Cytosolic fatty acid-binding proteins: subjects and tools in metabolic research

    Energy Technology Data Exchange (ETDEWEB)

    Binas, B. [Max Delbrueck Center for Molecular Medicine, Berlin-Buch (Germany)

    1998-12-31

    Fatty acid-binding proteins (FABPs) are major targets for specific binding of fatty acids in vivo. They constitute a widely expressed family of genetically related, small cytosolic proteins which very likely mediate intracellular transport of free long chain fatty acids. Genetic inhibition of FABP expression in vivo should therefore provide a useful tool to investigate and engineer fatty acid metabolism. (orig.) [Deutsch] Fettsaeurebindungsproteine (FABPs) sind wichtige Bindungsstellen fuer Fettsaeuren in vivo; sie bilden eine breit exprimierte Familie genetisch verwandter kleiner Zytosoleiweisse, die sehr wahrscheinlich den intrazellulaeren Transport unveresterter langkettiger Fettsaeuren vermitteln. Die genetische Hemmung der FABP-Expanssion in vivo bietet sich deshalb als Werkzeug zur Erforschung und gezielten Veraenderung des Fettsaeurestoffwechsels an. (orig.)

  11. Genetic Investigation of Tricarboxylic Acid Metabolism during the Plasmodium falciparum Life Cycle

    Directory of Open Access Journals (Sweden)

    Hangjun Ke

    2015-04-01

    Full Text Available New antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO lines that delete six of the eight mitochondrial tricarboxylic acid (TCA cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate-dehydrogenase-deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of 13C-isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development.

  12. Genetic investigation of tricarboxylic acid metabolism during the Plasmodium falciparum life cycle.

    Science.gov (United States)

    Ke, Hangjun; Lewis, Ian A; Morrisey, Joanne M; McLean, Kyle J; Ganesan, Suresh M; Painter, Heather J; Mather, Michael W; Jacobs-Lorena, Marcelo; Llinás, Manuel; Vaidya, Akhil B

    2015-04-07

    New antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO) lines that delete six of the eight mitochondrial tricarboxylic acid (TCA) cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate-dehydrogenase-deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of (13)C-isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Metabolic variations of fatty acid in isolated rat heart reperfused after a transient global ischemia

    International Nuclear Information System (INIS)

    Huang Gang; Michel Comet; Zhao Huiyang; Zhu Cuiying; Yuan Jimin

    1998-01-01

    Purpose: The fatty acid metabolism and the effect of glucose on it were studied in isolated and reperfused rat heat. Methods: 32 isolated working rat hearts were perfused in Langengdorff device with modified Krebs and were divided into normal and ischemia-reperfused group. Each group was also classified into two subgroups, modified krebs with or without glucose subgroup. 131 I-HA was injected into aorta of isolated working rat heart and then the radio-residue curves were acquired. Results: When the isolated rat hearts were perfused with krebs plus glucose, the catabolism of fatty acid was significantly decreased in normal group, but a remarkable increase of fatty acid catabolism was found in ischemia-reperfused group. While the isolated rat hearts were perfused with krebs without glucose, the catabolism of fatty acid in ischemia-reperfused isolated rat hearts were perfused with krebs without glucose, the catabolism of fatty acid in ischemia-reperfused isolated rat heart was less than that in normal group. Conclusions: Transient ischemia damages the catabolism of myocardial fatty acid in mitochondria in some degree. In normal isolated working rat heart, the principal energy source is glucose. However, the major energy source is switched to catabolism of fatty acid in ischemia-reperfused isolated rat heart. This phenomenon may be related to compensative increase of fatty acid catabolism for replenishing the loss of energy during ischemia

  14. Amino Acid Metabolism in Acute Renal Failure: Influence of Intravenous Essential L-Amino Acid Hyperalimentation Therapy

    Science.gov (United States)

    Abel, Ronald M.; Shih, Vivian E.; Abbott, William M.; Beck, Clyde H.; Fischer, Josef E.

    1974-01-01

    A solution of 8 essential I-amino acids and hypertonic dextrose was administered to 5 patients in acute postoperative renal failure in a program of hyperalimentation designed to decrease the patient's catabolic state and to accrue certain metabolic benefits. A sixth patient receiving intravenous glucose alone served as a control. The pretreatment plasma concentrations of amino acids in all 6 patients did not differ significantly from normal; following intravenous essential amino acids at a dose of approximately 12.6 gm/24 hours, no significant elevations out of the normal range of these substances occurred. Since urinary excretion rates did not dramatically increase, urinary loss was excluded as a possible cause for the failure of increase of plasma concentrations. The results suggest that the administration of an intravenous solution of 1-amino acids and hypertonic dextrose is associated with rapid clearance from the blood of these substances and, with a failure of increased urinary excretion, indirect evidence of amino acid utilization for protein synthesis has been obtained. Histidine supplementation in patients with acute renal failure is probably unnecessary based on the lack of significant decreases in histidine concentrations in these patients. PMID:4850497

  15. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR

    Directory of Open Access Journals (Sweden)

    Kavita Jadhav

    2018-03-01

    Full Text Available Objectives: Activation of the bile acid (BA receptors farnesoid X receptor (FXR or G protein-coupled bile acid receptor (GPBAR1; TGR5 improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. Methods: Wild-type (WT, Tgr5−/−, Fxr−/−, Apoe−/− and Shp−/− mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. Results: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD. Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (CEBPα as novel FXR-regulated genes. FXR inhibited PPARγ expression by inducing small heterodimer partner (SHP whereas the inhibition of CEBPα by FXR was SHP-independent. Conclusions: BA receptor activation can reverse obesity, NAFLD, and atherosclerosis by specific activation of FXR or TGR5. Our data suggest that, compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders. Keywords: Farnesoid X receptor, TGR5, Atherosclerosis, Obesity, NAFLD

  16. Correlation between citric acid and nitrate metabolisms during CAM cycle in the atmospheric bromeliad Tillandsia pohliana.

    Science.gov (United States)

    Freschi, Luciano; Rodrigues, Maria Aurineide; Tiné, Marco Aurélio Silva; Mercier, Helenice

    2010-12-15

    Crassulacean acid metabolism (CAM) confers crucial adaptations for plants living under frequent environmental stresses. A wide metabolic plasticity can be found among CAM species regarding the type of storage carbohydrate, organic acid accumulated at night and decarboxylating system. Consequently, many aspects of the CAM pathway control are still elusive while the impact of this photosynthetic adaptation on nitrogen metabolism has remained largely unexplored. In this study, we investigated a possible link between the CAM cycle and the nitrogen assimilation in the atmospheric bromeliad Tillandsia pohliana by simultaneously characterizing the diel changes in key enzyme activities and metabolite levels of both organic acid and nitrate metabolisms. The results revealed that T. pohliana performed a typical CAM cycle in which phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase phosphorylation seemed to play a crucial role to avoid futile cycles of carboxylation and decarboxylation. Unlike all other bromeliads previously investigated, almost equimolar concentrations of malate and citrate were accumulated at night. Moreover, a marked nocturnal depletion in the starch reservoirs and an atypical pattern of nitrate reduction restricted to the nighttime were also observed. Since reduction and assimilation of nitrate requires a massive supply of reducing power and energy and considering that T. pohliana lives overexposed to the sunlight, we hypothesize that citrate decarboxylation might be an accessory mechanism to increase internal CO₂ concentration during the day while its biosynthesis could provide NADH and ATP for nocturnal assimilation of nitrate. Therefore, besides delivering photoprotection during the day, citrate might represent a key component connecting both CAM pathway and nitrogen metabolism in T. pohliana; a scenario that certainly deserves further study not only in this species but also in other CAM plants that nocturnally accumulate citrate

  17. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  18. Metabolism of very long-chain Fatty acids: genes and pathophysiology.

    Science.gov (United States)

    Sassa, Takayuki; Kihara, Akio

    2014-02-01

    Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology.

  19. Urea application promotes amino acid metabolism and membrane lipid peroxidation in Azolla.

    Directory of Open Access Journals (Sweden)

    Jiana Chen

    Full Text Available A pot experiment was conducted to evaluate the effect of urea on nitrogen metabolism and membrane lipid peroxidation in Azolla pinnata. Compared to controls, the application of urea to A. pinnata resulted in a 44% decrease in nitrogenase activity, no significant change in glutamine synthetase activity, 660% higher glutamic-pyruvic transaminase, 39% increase in free amino acid levels, 22% increase in malondialdehyde levels, 21% increase in Na+/K+- levels, 16% increase in Ca2+/Mg2+-ATPase levels, and 11% decrease in superoxide dismutase activity. In terms of H2O2 detoxifying enzymes, peroxidase activity did not change and catalase activity increased by 64% in urea-treated A. pinnata. These findings suggest that urea application promotes amino acid metabolism and membrane lipid peroxidation in A. pinnata.

  20. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

    1986-08-01

    The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid /sup 14/C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

  1. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

    International Nuclear Information System (INIS)

    Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

    1986-01-01

    The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14 C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides. (orig.)

  2. Urea application promotes amino acid metabolism and membrane lipid peroxidation in Azolla.

    Science.gov (United States)

    Chen, Jiana; Huang, Min; Cao, Fangbo; Pardha-Saradhi, P; Zou, Yingbin

    2017-01-01

    A pot experiment was conducted to evaluate the effect of urea on nitrogen metabolism and membrane lipid peroxidation in Azolla pinnata. Compared to controls, the application of urea to A. pinnata resulted in a 44% decrease in nitrogenase activity, no significant change in glutamine synthetase activity, 660% higher glutamic-pyruvic transaminase, 39% increase in free amino acid levels, 22% increase in malondialdehyde levels, 21% increase in Na+/K+- levels, 16% increase in Ca2+/Mg2+-ATPase levels, and 11% decrease in superoxide dismutase activity. In terms of H2O2 detoxifying enzymes, peroxidase activity did not change and catalase activity increased by 64% in urea-treated A. pinnata. These findings suggest that urea application promotes amino acid metabolism and membrane lipid peroxidation in A. pinnata.

  3. Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

    Science.gov (United States)

    Yamauchi, S; Takeishi, Y; Minamihaba, O; Arimoto, T; Hirono, O; Takahashi, H; Miyamoto, T; Nitobe, J; Nozaki, N; Tachibana, H; Watanabe, T; Fukui, A; Kubota, I

    2003-08-01

    This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (Pacid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

  4. Abscisic acid as a factor in regulation of photosynthetic carbon metabolism of pea seedlings

    Directory of Open Access Journals (Sweden)

    Maria Faltynowicz

    2014-01-01

    Full Text Available The influence of abscisic acid (ABA on carbon metabolism and the activity of ribulosebisphosphate (RuBP and phosphoenolpyruvate (PEP carboxylases in 8-day-old pea seedlings was investigated. It was endeavoured to correlate the changes observed in metabolic processes with the endogenous ABA level. In plants treated with ABA incorporation of labeled carbon into sucrose, glucose, fructose and sugar phosphates was depressed, while 14C incorporation into starch, ribulose and malic acid was enhanced. The activity of RuBP carboxylase was considerably lowered, whereas that of PEP carboxylase was slightly increased. It is considered that inhibition of photosynthesis due to the action of ABA is caused to a great extent by the obstruction of the C-3 pathway and reduced activity of RuBP carboxylase, whereas (β-carboxylation was not blocked.

  5. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

    DEFF Research Database (Denmark)

    Mourtzakis, M.; Graham, T.E.; Gonzalez-Alonso, J.

    2008-01-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate...... declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70......% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (Pglutamate infusion. Peak...

  6. Lactobacillus acidophilus NCFM affects vitamin E acetate metabolism and intestinal bile acid signature in monocolonized mice

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Sulek, Karolina; Skov, Kasper

    2014-01-01

    (NCFM) on the intestinal metabolome (jejunum, caecum, and colon) in mice by comparing NCFM mono-colonized (MC) mice with GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice...... by deconjugation and dehydroxylation of bile acids. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine. Especially, the digestion of larger carbohydrates (penta- and tetrasaccharides) was increased in MC mice. Interestingly, we also found vitamin E (α...

  7. Involvement of triacylglycerol in the metabolism of fatty acids by cultured neuroblastoma and glioma cells

    International Nuclear Information System (INIS)

    Cook, H.W.; Clarke, J.T.; Spence, M.W.

    1982-01-01

    The metabolism (chain elongation, desaturation, and incorporation into complex lipids) of thirteen different radiolabeled fatty acids and acetate was examined in N1E-115 neuroblastoma and C-6 glioma cell lines in culture. During 6-hr incubations, all fatty acids were extensively (14-80%) esterified to complex lipids, mainly choline phosphoglycerides and triacylglycerol. With trienoic and tetraenoic substrates, inositol and ethanolamine phosphoglycerides also contained up to 30% of the labeled fatty acids; plasmalogen contained up to half of the label in the ethanolamine phosphoglyceride fraction of neuroblastoma cells. Chain elongation and delta 9, delta 6, and delta 5 desaturation occurred in both cell lines; delta 4 desaturation was not observed. Seemingly anomalous utilization of arachidic acid and some selectivity based on the geometric configuration of double bonds was observed. These studies indicate that these cell lines are capable of modulating cellular membrane composition by a combination of selective exclusion and removal of inappropriate acyl chains and of modification of other acyl chains by desaturation and chain elongation. The time courses and patterns of modification and incorporation of exogenous substrates into phospholipids and triacylglycerol suggest that exogenous unsaturated fatty acid may be incorporated into triacylglycerol and later released for further metabolism and incorporation into phospholipids. This supports a role for triacylglycerol in the synthesis of membrane complex lipids in cell lines derived from neural tissue

  8. Effects of cadmium stress on growth and amino acid metabolism in two Compositae plants.

    Science.gov (United States)

    Zhu, Guangxu; Xiao, Huayun; Guo, Qingjun; Zhang, Zhongyi; Zhao, Jingjing; Yang, Dan

    2018-08-30

    Cadmium, a high toxic heavy metal, is one of the most serious contaminants in soil and a potential threat to plant growth and human health. Amino acid metabolism has the central role in heavy metal stress resistance of plants. In this paper, a pot experiment was carried out to study the effects of different concentrations of cadmium (0, 3, 6, 12, 30 mg kg -1 ) on the growth, Cd accumulation and amino acid metabolism in two Compositae plants (Ageratum conyzoides L. and Crassocephalum crepidioides). The results showed that under cadmium stress, C. crepidioides accumulated more Cd in its shoot and was tolerant to Cd, whereas its low Cd-accumulating relative, A. conyzoides, suffered reduced growth. The Cd content in the aerial part of C. crepidioides exceeded the threshold of Cd-hyperaccumulator. Furthermore, the bioaccumulation factor (BCF) and biological transfer factor (BTF) values for Cd in C. crepidioides were > 1. Thus, C. crepidioides can be regarded as Cd-hyperaccumulator. The comparison between both studied plants indicated that Cd stress resulted in a differential but coordinated response of amino acid levels, which are playing a significant role in plant adaptation to Cd stress. Glu, Gln, Asp, Asn, Gaba, Val and Ala dominated the major amino acids. Higher Cd tolerance and Cd accumulation in C. crepidioides was associated with greater accumulation of free amino acids, especially for Gln and Asn, in C. crepidioides than in A. conyzoides. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. 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.

  10. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  11. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

  12. Free fatty acid receptors and their role in regulation of energy metabolism.

    Science.gov (United States)

    Hara, Takafumi; Kimura, Ikuo; Inoue, Daisuke; Ichimura, Atsuhiko; Hirasawa, Akira

    2013-01-01

    The free fatty acid receptor (FFAR) is a G protein-coupled receptor (GPCR) activated by free fatty acids (FFAs), which play important roles not only as essential nutritional components but also as signaling molecules in numerous physiological processes. In the last decade, FFARs have been identified by the GPCR deorphanization strategy derived from the human genome database. To date, several FFARs have been identified and characterized as critical components in various physiological processes. FFARs are categorized according to the chain length of FFA ligands that activate each FFAR; FFA2 and FFA3 are activated by short chain FFAs, GPR84 is activated by medium-chain FFAs, whereas FFA1 and GPR120 are activated by medium- or long-chain FFAs. FFARs appear to act as physiological sensors for food-derived FFAs and digestion products in the gastrointestinal tract. Moreover, they are considered to be involved in the regulation of energy metabolism mediated by the secretion of insulin and incretin hormones and by the regulation of the sympathetic nerve systems, taste preferences, and inflammatory responses related to insulin resistance. Therefore, because FFARs can be considered to play important roles in physiological processes and various pathophysiological processes, FFARs have been targeted in therapeutic strategies for the treatment of metabolic disorders including type 2 diabetes and metabolic syndrome. In this review, we present a summary of recent progress regarding the understanding of their physiological roles in the regulation of energy metabolism and their potential as therapeutic targets.

  13. Time-course of myocardial perfusion and fatty acid metabolism after coronary reperfusion

    International Nuclear Information System (INIS)

    Sochor, H.; Pachinger, O.; Ogris, E.; Probst, P.; Kaindl, F.

    1985-01-01

    To investigate the relationship and time-course of myocardial perfusion and behaviour of fatty acid uptake and clearance following reperfusion, the authors studied 19 patients after successful intracoronary thrombolysis with Tl-201 and I-123 hepta-decanoic acid (HDA) and planar imaging. Pts were studied acute (A: 48 hours), early (E:6-8 days) and late (L:6-12 months). %-defect size and relative tracer uptake were determined for both markers as well as t1/2 of the early clearance phase for HDA. Late Tl was done as stress test study after dipyridamole infusion. As in a previous report acute HDA uptake-defects were larger than Tl (38 +- 10% vs 24 +- 9%, p<0.05) suggesting a larger area of metabolic impairment than outlined by perfusion. HDA and Tl uptake at A correlated significantly (p<0.01, r=0.86) but HDA uptake was 19% lower than Tl and not different at E and L. Tl stress studies exhibited in 74% reversible ischemia in the area of ''metabolic recovery''. The authors conclude that early after reperfusion uptake of HDA is frequently impaired despite improved perfusion suggesting metabolic derangement showing a slow recovery over time. A multiple tracer approach including metabolic markers may improve the characterization of reperfused myocardium

  14. Analysis of Growth Inhibition and Metabolism of Hydroxycinnamic Acids by Brewing and Spoilage Strains of Brettanomyces Yeast

    Directory of Open Access Journals (Sweden)

    Michael Lentz

    2015-10-01

    Full Text Available Brettanomyces yeasts are well-known as spoilage organisms in both the wine and beer industries, but also contribute important desirable characters to certain beer styles. These properties are mediated in large part by Brettanomyces’ metabolism of hydroxycinnamic acids (HCAs present in beverage raw materials. Here we compare growth inhibition by, and metabolism of, HCAs among commercial brewing strains and spoilage strains of B. bruxellensis and B. anomalus. These properties vary widely among the different strains tested and between the HCAs analyzed. Brewing strains showed more efficient metabolism of ferulic acid over p-coumaric acid, a trait not shared among the spoilage strains.

  15. Analysis of Growth Inhibition and Metabolism of Hydroxycinnamic Acids by Brewing and Spoilage Strains of Brettanomyces Yeast.

    Science.gov (United States)

    Lentz, Michael; Harris, Chad

    2015-10-15

    Brettanomyces yeasts are well-known as spoilage organisms in both the wine and beer industries, but also contribute important desirable characters to certain beer styles. These properties are mediated in large part by Brettanomyces ' metabolism of hydroxycinnamic acids (HCAs) present in beverage raw materials. Here we compare growth inhibition by, and metabolism of, HCAs among commercial brewing strains and spoilage strains of B. bruxellensis and B. anomalus . These properties vary widely among the different strains tested and between the HCAs analyzed. Brewing strains showed more efficient metabolism of ferulic acid over p -coumaric acid, a trait not shared among the spoilage strains.

  16. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    OpenAIRE

    Samman S; Crossett B; Somers M; Bell KJ; Lai NT; Sullivan DR; Petocz P

    2014-01-01

    Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA) status is determined by facto...

  17. 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 ...

  18. SULPHUR-CONTAINING AMINO ACIDS METABOLISM IN EXPERIMENTAL HYPER- AND HYPOTHYROIDISM IN RATS.

    Science.gov (United States)

    Nechiporuk, V; Zaichko, N; Korda, М; Melnyk, A; Koloshko, O

    2017-10-01

    Hyper- and hypothyroidism are some of the most common endocrinopathies that cause many metabolic disorders including amino acids metabolism. However, a specific molecular mechanism of thyroid hormones influence on sulphur-containing amino acids metabolism has not been established. The aim of our research was to investigate experimentally the influence of thyroid gland functional state on the main enzymatic systems of sulphur-containing amino acids metabolism in liver and kidneys, the content of homocysteine, cysteine and H2S in blood. The rats were administered with L-thyroxine and mercazolil to simulate the states of hyper- and hypothyroidism, which were confirmed by the content of fT3, fT4 and TSH in the blood. In liver and kidneys of the animals with hypothyroidism we observed the decrease in the activity of enzymes of remethylation cycle of S-adenosylmethioninsyntase, S-adenosylhomocysteinhyhdrolase, betaine-homocysteine methyltransferase. Suppression of transsulfuration transformation of homocysteine to cysteine in hypothyroidism was mainly due to the inhibition of cystathionine synthase activity of cystathionine-β-synthase, wherein cystathionase activity of cystathionine-γ-lyase was not changed. In animals with hypothyroidism we also noticed the inhibition of cysteine desulfunation reactions: the activity of enzymes of cystathionine-β-synthase, cystathionine-γ-lyase and cysteine aminotransferase significantly decreased in liver and kidneys. Experimental hyperthyroidism was accompanied by increase in activity of remethylation cycle enzymes, increase in cystationine synthase activity of cystathionine-β-synthase in liver and activity of these enzymes in kidneys. The simulation of hyperthyroidism led to the decrease of homocysteine concentration, and of hypothyroidism - to the increase of homocysteine and cysteine concentrations and reduced H2S content in blood of the animals. Thus, the significant risk factors for the development of atherosclerosis

  19. Induction of peroxisomal beta-oxidation by a microbial catabolite of cholic acid in rat liver and cultured rat hepatocytes.

    Science.gov (United States)

    Nishimaki-Mogami, T; Takahashi, A; Toyoda, K; Hayashi, Y

    1993-01-01

    The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta-oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine. PMID:8216219

  20. Direct determination of mercury in cosmetic samples by isotope dilution inductively coupled plasma mass spectrometry after dissolution with formic acid

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Ying; Shi, Zeming; Zong, Qinxia; Wu, Peng; Su, Jing [Sichuan Provincial Key Laboratory of Nuclear Technology in Geology, College of Nuclear Technology and Automation Engineering, Chengdu University of Technology, Chengdu 610059 (China); Liu, Rui, E-mail: liur.ray@gmail.com [Mineral Resources Chemistry Key Laboratory of Sichuan Higher Education Institutions, College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, Chengdu 610059 (China)

    2014-02-17

    Graphical abstract: -- Highlights: •Simple, sensitive, and accurate method is established for mercury determination in cosmetics. •The sample preparation procedure is highly simplified. •Isotope dilution efficiently eliminates matrix effect. •First report of using formic acid based method in combination with PVG-ID-ICP MS for mercury quantitation in cosmetics. -- Abstract: A new method was proposed for the accurate determination of mercury in cosmetic samples based on isotopic dilution (ID)-photochemical vapor generation (PVG)-inductively coupled plasma mass spectrometry (ICP MS) measurement. Cosmetic samples were directly dissolved in formic acid solution and subsequently subjected to PVG for the reduction of mercury into vapor species following by ICP MS detection. Therefore, the risks of analyte contamination and loss were avoided. Highly enriched {sup 201}Hg isotopic spike is added to cosmetics and the isotope ratios of {sup 201}Hg/{sup 202}Hg were measured for the quantitation of mercury. With ID calibration, the influences originating from sample matrixes for the determination of mercury in cosmetic samples have been efficiently eliminated. The effects of several experimental parameters, such as the concentration of the formic acid, and the flow rates of carrier gas and sample were investigated. The method provided good reproducibility and the detection limits were found to be 0.6 pg mL{sup −1}. Finally, the developed method was successfully applied for the determination of mercury in six cosmetic samples and a spike test was performed to verify the accuracy of the method.

  1. Is myocardial fatty acid metabolism different between hypertrophic cardiomyopathy and hypertensive hypertrophy?

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Usami, Masahisa; Honda, Minoru

    1994-01-01

    To investigate characteristics of fatty acid metabolism in hypertrophic cardiomyopathy (HCM), we performed myocardial imaging with 123 I-iodophenyl-3-methylpentadecanoic acid (BMIPP) in 24 HCM patients, 13 patients with hypertensive hypertrophy (HT) and 10 normal subjects. Rest myocardial imaging with 123 I-BMIPP was obtained at 20 minutes and 3 hours after 123 I-BMIPP injection. Rest 201 Tl imaging was also performed. In addition to ordinary tomography, whole body imaging was performed to calculate %Uptake (percentage of cardiac uptake of the isotope to total injected dose). As global indexes of fatty acid metabolism, we calculated two parameters; Uptake Ratio (%Uptake of 123 I-BMIPP normalized by myocardial perfusion) and WOR (percent reduction of myocardial 123 I-BMIPP within 3 hours). Regional abnormality was evaluated by visual assessment of ordinary tomograms and by BMIPP/Tl map. BMIPP/Tl map was made from Bull's-eye maps of 123 I-BMIPP and 201 Tl, and it represented 123 I-BMIPP uptake normalized by myocardial perfusion of each pixel which constructed the image. %Uptake of 123 I-BMIPP was not different among three groups. Uptake Ratio was significantly (p HT (1.03±0.08)>HCM (0.87±0.09). WOR of 123 I-BMIPP was accerelated in HCM (12.7±4.7%) and HT (10.2±2.9%) compared with normal (5.1±3.1%) (p 123 I-BMIPP distribution was found in 17 of 24 patients (71%) including 3 patients with equivocal abnormality. In HT patients, only equivocal abnormality was observed in 23%. In BMIPP/Tl map, abnormality was observed in 92% of HCM and 8% of HT. Although global myocardial fatty acid metabolism was equally disturbed both in HCM and HT, regional abnormality of fatty acid metabolism was observed preferetially in HCM. This indicated myocardial fatty acid metabolism was not identical between HCM and HT. (author)

  2. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  3. Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation.

    Science.gov (United States)

    Liu, Yong; He, Yizhou; Jin, Aiwen; Tikunov, Andrey P; Zhou, Lishi; Tollini, Laura A; Leslie, Patrick; Kim, Tae-Hyung; Li, Lei O; Coleman, Rosalind A; Gu, Zhennan; Chen, Yong Q; Macdonald, Jeffrey M; Graves, Lee M; Zhang, Yanping

    2014-06-10

    The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis. Although the Mdm2(C305F) mutation does not significantly affect growth and development in mice, this mutation promotes fat accumulation under normal feeding conditions and hepatosteatosis under acute fasting conditions. We show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2 interaction, and induces p53-mediated transactivation of malonyl-CoA decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl-CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to decreased oxidative respiration and increased fatty acid accumulation in the liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor responsible for stimulating fatty acid oxidation in response to nutrient depletion.

  4. Metabolism in humans of cis-12,trans-15-octadecadienoic acid relative to palmitic, stearic, oleic and linoleic acids

    International Nuclear Information System (INIS)

    Emken, E.A.; Rohwedder, W.K.; Adlof, R.O.; Rakoff, H.; Gulley, R.M.

    1987-01-01

    Mixtures of triglycerides containing deuterium-labeled hexadecanoic acid (16:0), octadecanoic acid (18:0), cis-9-octadecenoic acid (9c-18:1), cis-9,cis-12-octadecadienoic acid (9c, 12c-18:2) and cis-12,trans-15-octadecadienoic acid (12c,15t-18:2) were fed to two young-adult males. Plasma lipid classes were isolated from samples collected periodically over 48 hr. Incorporation and turnover of the deuterium-labeled fats in plasma lipids were followed by gas chromatography-mass spectrometry (GC-MS) analysis of the methyl ester derivatives. Absorption of the deuterated fats was followed by GC-MS analysis of chylomicron triglycerides isolated by ultracentrifugation. Results were the following: (i) endogenous fat contributed about 40% of the total fat incorporated into chylomicron triglycerides; (ii) elongation, desaturation and chain-shortened products from the deuterated fats were not detected; (iii) the polyunsaturated isomer 12c,15t-18:2 was metabolically more similar to saturated and 9c-18:1 fatty acids than to 9c,12c-18:2; (iv) relative incorporation of 9c,12c-18:2 into phospholipids did not increase proportionally with an increase of 9c,12c-18:2 in the mixture of deuterated fats fed; (v) absorption of 16:0, 18:0, 9c-18:1, 9c,12c-18:2 and 12c,15t-18:2 were similar; and (vi) data for the 1- and 2-acyl positions of phosphatidylcholine and for cholesteryl ester fractions reflected the known high specificity of phosphatidylcholine acyltransferase and lecithin:cholesteryl acyltransferase for 9c,12c-18:2. These results illustrate that incorporation of dietary fatty acids into human plasma lipid classes is selectively controlled and that incorporation of dietary 9c,12c-18:2 is limited

  5. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    Directory of Open Access Journals (Sweden)

    Marijana Todorčević

    2015-12-01

    Full Text Available Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3 and docosahexaenoic acid (DHA; 22:6n-3. Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity.

  6. Essential amino acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    Mazariegos, M.; De Vettorazzi, C.; Solomons, N.W.; Caballero, B.

    1994-01-01

    Traditional methods used to evaluate protein metabolism left unanswered some of the relevant questions in public health in developing countries, such as growth retardation in children. Particularly, in developing countries, infection (clinical and subclinical) and malnutrition are still relevant problems, and the most important scientific issues for the application of stable isotope tracer methods are related to the impact of infection, such as the oxidative disposal of essential amino acids in well-nourished and malnourished children. The objectives of the present proposal are: (1) To simplify, make less expensive, less time-consuming, and less invasive, methods in clinical research on amino acid metabolism using stable-isotope tracers in children; and (2) To assess the effects of infection (clinical or subclinical) on whole-body protein turnover in children with and without malnutrition. The objectives involve the engineering and assessment of a portable instrument to be used in evaluations of protein oxidation in the developing world. Methodological issues such as intra- and inter-subject variability, which are of great importance for the interpretation of amino acid metabolism and protein turnover, will also be considered. 18 refs, 2 figs

  7. Metabolic Regulation of Manganese Superoxide Dismutase Expression via Essential Amino Acid Deprivation*

    Science.gov (United States)

    Aiken, Kimberly J.; Bickford, Justin S.; Kilberg, Michael S.; Nick, Harry S.

    2008-01-01

    Organisms respond to available nutrient levels by rapidly adjusting metabolic flux, in part through changes in gene expression. A consequence of adaptations in metabolic rate is the production of mitochondria-derived reactive oxygen species. Therefore, we hypothesized that nutrient sensing could regulate the synthesis of the primary defense of the cell against superoxide radicals, manganese superoxide dismutase. Our data establish a novel nutrient-sensing pathway for manganese superoxide dismutase expression mediated through essential amino acid depletion concurrent with an increase in cellular viability. Most relevantly, our results are divergent from current mechanisms governing amino acid-dependent gene regulation. This pathway requires the presence of glutamine, signaling via the tricarboxylic acid cycle/electron transport chain, an intact mitochondrial membrane potential, and the activity of both the MEK/ERK and mammalian target of rapamycin kinases. Our results provide evidence for convergence of metabolic cues with nutrient control of antioxidant gene regulation, revealing a potential signaling strategy that impacts free radical-mediated mutations with implications in cancer and aging. PMID:18187411

  8. Metabolic regulation of manganese superoxide dismutase expression via essential amino acid deprivation.

    Science.gov (United States)

    Aiken, Kimberly J; Bickford, Justin S; Kilberg, Michael S; Nick, Harry S

    2008-04-18

    Organisms respond to available nutrient levels by rapidly adjusting metabolic flux, in part through changes in gene expression. A consequence of adaptations in metabolic rate is the production of mitochondria-derived reactive oxygen species. Therefore, we hypothesized that nutrient sensing could regulate the synthesis of the primary defense of the cell against superoxide radicals, manganese superoxide dismutase. Our data establish a novel nutrient-sensing pathway for manganese superoxide dismutase expression mediated through essential amino acid depletion concurrent with an increase in cellular viability. Most relevantly, our results are divergent from current mechanisms governing amino acid-dependent gene regulation. This pathway requires the presence of glutamine, signaling via the tricarboxylic acid cycle/electron transport chain, an intact mitochondrial membrane potential, and the activity of both the MEK/ERK and mammalian target of rapamycin kinases. Our results provide evidence for convergence of metabolic cues with nutrient control of antioxidant gene regulation, revealing a potential signaling strategy that impacts free radical-mediated mutations with implications in cancer and aging.

  9. Essential amino acid metabolism in infected/non-infected, poor, Guatemalan children

    Energy Technology Data Exchange (ETDEWEB)

    Mazariegos, M; De Vettorazzi, C; Solomons, N W [Hospital de Ojos y Oidos ` ` Dr. Rodolfo Robles V.` ` , Guatemala City (Guatemala). Centre for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM); Caballero, B [Johns Hopkins Univ., Baltimore, MD (United States). Centre for Human Nutrition

    1994-12-31

    Traditional methods used to evaluate protein metabolism left unanswered some of the relevant questions in public health in developing countries, such as growth retardation in children. Particularly, in developing countries, infection (clinical and subclinical) and malnutrition are still relevant problems, and the most important scientific issues for the application of stable isotope tracer methods are related to the impact of infection, such as the oxidative disposal of essential amino acids in well-nourished and malnourished children. The objectives of the present proposal are: (1) To simplify, make less expensive, less time-consuming, and less invasive, methods in clinical research on amino acid metabolism using stable-isotope tracers in children; and (2) To assess the effects of infection (clinical or subclinical) on whole-body protein turnover in children with and without malnutrition. The objectives involve the engineering and assessment of a portable instrument to be used in evaluations of protein oxidation in the developing world. Methodological issues such as intra- and inter-subject variability, which are of great importance for the interpretation of amino acid metabolism and protein turnover, will also be considered. 18 refs, 2 figs.

  10. Pain and beyond: fatty acid amides and fatty acid amide hydrolase inhibitors in cardiovascular and metabolic diseases.

    Science.gov (United States)

    Pillarisetti, Sivaram; Alexander, Christopher W; Khanna, Ish

    2009-12-01

    Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of several important endogenous fatty acid amides (FAAs), including anandamide, oleoylethanolamide and palmitoylethanolamide. Because specific FAAs interact with cannabinoid and vanilloid receptors, they are often referred to as 'endocannabinoids' or 'endovanilloids'. Initial interest in this area, therefore, has focused on developing FAAH inhibitors to augment the actions of FAAs and reduce pain. However, recent literature has shown that these FAAs - through interactions with unique receptors (extracellular and intracellular) - can induce a diverse array of effects that include appetite suppression, modulation of lipid and glucose metabolism, vasodilation, cardiac function and inflammation. This review gives an overview of FAAs and diverse FAAH inhibitors and their potential therapeutic utility in pain and non-pain indications.

  11. Lipid and fatty acid metabolism in Ralstonia eutropha: relevance for the biotechnological production of value-added products.

    Science.gov (United States)

    Riedel, Sebastian L; Lu, Jingnan; Stahl, Ulf; Brigham, Christopher J

    2014-02-01

    Lipid and fatty acid metabolism has been well studied in model microbial organisms like Escherichia coli and Bacillus subtilis. The major precursor of fatty acid biosynthesis is also the major product of fatty acid degradation (β-oxidation), acetyl-CoA, which is a key metabolite for all organisms. Controlling carbon flux to fatty acid biosynthesis and from β-oxidation allows for the biosynthesis of natural products of biotechnological importance. Ralstonia eutropha can utilize acetyl-CoA from fatty acid metabolism to produce intracellular polyhydroxyalkanoate (PHA). R. eutropha can also be engineered to utilize fatty acid metabolism intermediates to produce different PHA precursors. Metabolism of lipids and fatty acids can be rerouted to convert carbon into other value-added compounds like biofuels. This review discusses the lipid and fatty acid metabolic pathways in R. eutropha and how they can be used to construct reagents for the biosynthesis of products of industrial importance. Specifically, how the use of lipids or fatty acids as the sole carbon source in R. eutropha cultures adds value to these biotechnological products will be discussed here.

  12. Effects of Lysine deficiency and Lys-Lys dipeptide on cellular apoptosis and amino acids metabolism.

    Science.gov (United States)

    Yin, Jie; Li, Yuying; Han, Hui; Zheng, Jie; Wang, Lijian; Ren, Wenkai; Chen, Shuai; Wu, Fei; Fang, Rejun; Huang, Xingguo; Li, Chunyong; Tan, Bie; Xiong, Xia; Zhang, Yuzhe; Liu, Gang; Yao, Jiming; Li, Tiejun; Yin, Yulong

    2017-09-01

    Lysine (Lys) is a common limiting amino acids (AA) for humans and animals and plays an important role in cell proliferation and metabolism, while metabolism of Lys deficiency and its dipeptide is still obscure. Thus, this study mainly investigated the effects of Lys deficiency and Lys-Lys dipeptide on apoptosis and AA metabolism in vitro and in vivo models. Lys deficiency induced cell-cycle arrest and apoptosis and upregulated Lys transporters in vitro and in vivo. SLC7A11, a cystine-glutamate antiporter, was markedly upregulated by Lys deficiency and then further mediated cystine uptake and glutamate release, which was negatively regulated by cystine and glutamate transporters. Meanwhile, Lys deprivation upregulated pept1 expression, which might improve Lys-Lys dipeptide absorption to compensate for the reduced Lys availability. Lys-Lys dipeptide alleviated Lys deficiency induced cell-cycle arrest and apoptosis and influenced AA metabolism. Furthermore, the mammalian target of rapamycin signal might be involved in sensing cellular Lys starvation and Lys-Lys dipeptide. Altogether, these studies suggest that Lys deficiency impairs AA metabolism and causes apoptosis. Lys-Lys dipeptide serves as a Lys source and alleviates Lys deficiency induced cellular imbalance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Metabolism of γ-hydroxyl-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids

    International Nuclear Information System (INIS)

    Doherty, J.D.; Roth, R.H.

    1978-01-01

    Ninhydrin decarboxylation experiments were carried out on the labelled amino acids produced following intraventricular injection of either γ-hydroxy-[1- 14 C] butyric acid (GHB) or [1- 14 C] succinate. The loss of isotope (as 14 CO 2 ) was similar for both substances. The [1- 14 C] GHB metabolites lost 75% of the label and the [1- 14 C] succinate metabolites lost 68%. This observation gives support to the hypothesis that the rat brain has the enzymatic capacity to metabolize [1- 14 C] GHB to succinate and to amino acids that have the isotope in the carboxylic acid group adjacent to the α-amino group. These results also indicate that the label from [1- 14 C] GHB does not enter the Krebs cycle as acetate. The specific activity ratio of radio-labelled glutamine to glutamic acid was determined in order to evaluate which of the two major metabolic compartments prefentially metabolize GHB. It was found that for [1- 14 C] GHB the ratio was 4.20 +- 0.18 (S.E. for n = 7) and for [1- 14 C] succinate the ratio was 7.71 (average of two trials, 7.74 and 7.69). These results suggest that the compartment thought to be associated with glial cells and synaptosomal structures is largely responsible for the metabolism of GHB. Metabolism as it might relate to the neuropharmacological action of GHB is discussed. (author)

  14. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    International Nuclear Information System (INIS)

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-01

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  15. Metabolism of 5,6-epoxyeicosatrienoic acid by the human platelet. Formation of novel thromboxane analogs.

    Science.gov (United States)

    Balazy, M

    1991-12-15

    Radiolabeled cis-(+-)-5,6-epoxyeicosatrienoic acid (5(6)-EpETrE) was incubated with a suspension of isolated human platelets in order to study its metabolic fate. The epoxide slowly disappeared from the suspension and was completely metabolized within 30 min. After extraction and analysis by reverse-phase high performance liquid chromatography, seven metabolites were found. Addition of either indomethacin (0.01 mM, cyclooxygenase inhibitor) or BW755C (0.1 mM, cyclooxygenase/lipoxygenase inhibitor) to the incubations blocked the formation of four and six metabolites, respectively, 1,2-Epoxy-3,3,3-trichloropropane (inhibitor of microsomal epoxide hydrolase) failed to inhibit the formation of 5,6-dihydroxyeicosatrienoic acid (5,6-DiHETrE), a hydrolysis product of the precursor 5(6)-EpETrE. The metabolites were characterized by UV spectroscopy, negative ion chemical ionization liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and, in one instance, coelution with synthetic standard. Three primary platelet metabolites were structurally determined to be 5,6-epoxy-12-hydroxyeicosatrienoic acid, 5,6-epoxy-12-hydroxyheptadecadienoic acid, and a unique bicyclic metabolite, 5-hydroxy-6,9-epoxy-thromboxane B1, which originated from intramolecular hydrolysis of 5,6-epoxythromboxane-B1. This thromboxane analog was partially separated into stereoisomers and coeluted with the racemic synthetic standard in gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Three other metabolites were characterized as 5,6,12-trihydroxyeicosatrienoic acid, 5,6,12-trihydroxyheptadecadienoic acid, and 5,6-dihydroxythromboxane-B1, and resulted from the hydrolysis of the corresponding epoxides rather than from the metabolism of 5,6-DiHETrE. The latter was not metabolized by platelet cyclooxygenase or lipoxygenase. The biosynthesis of two cyclooxygenase metabolites indicated the formation of unstable 5,6-epoxythromboxane-A1 as an intermediate

  16. Detailed predictive mapping of acid sulfate soil occurrence using electromagnetic induction data

    DEFF Research Database (Denmark)

    Beucher, Amélie; Boman, A; Mattbäck, S

    impact through the resulting corrosion of concrete and steel infrastructures, or their poor geotechnical qualities.Mapping acid sulfate soil occurrence thus constitutes a key step to target the strategic areas for subsequent environmental risk management and mitigation. Conventional mapping (i.e. soil...

  17. Multiple stable isotope tracer technique for studying the metabolic kinetics of amino acids in hepatic failure

    Energy Technology Data Exchange (ETDEWEB)

    Zongqin, Xia; Tengchang, Dai; Jianhua, Zhang; Yaer, Hu; Bingyao, Yu; Xingrong, Xu; Guanlu, Huang; Gengrong, Shen; Yaqiu, Zhou; Hong, Yu

    1987-08-01

    In order to study the mechanism of the imbalance of amino acid metabolism during hepatic failure, a stable isotope tracer method for observing simultaneously the metabolic kinetics of several amino acids has been established. /sup 15/N-L-Ala, (2,3-D/sub 3/)-Leu and (2,3-D/sub 3/)-Phe were chosen as nonessential, branched chain and aromatic amino acids. A single iv injection of 40 mg N-Ala, 20 mg deuterated Leu and 20 mg deuterated Phe was given to each human subject. Blood samples were taken just before and at different times (up to 60 min) after the injection. Total free amino acids were isolated from the plasma with a small dowex 50 x 8 column and converted to trifluoroacetyl derivatives. Their abundances were then analyzed with a GC-MS system and typical double exponential time course curves were found for all the three labelled amino acids. A two-pool model was designed and applied for compartmental analysis. Significant changes were found in the kinetic parameters of Phe and Leu in patients with fulminant hepatitis or heptic cirrhosis. The half-lives of both Phe pools were longer and the pool sizes were larger than normal subjects, while the half-lives and pool sizes of Leu changes in the opposite direction. No marked change was found in Ala. The significance of intracellular imbalance of Phe and Leu metabolism was discussed. It is evident that the combination of GCMS technique and multiple-tracers labelled with stable isotopes is of great potential for similar purposes.

  18. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    Wong, K.L.; Tyce, G.M.

    1983-01-01

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  19. Metabolic Engineering of Yeast to Produce Fatty Acid-derived Biofuels: Bottlenecks and Solutions

    Directory of Open Access Journals (Sweden)

    Jiayuan eSheng

    2015-06-01

    Full Text Available Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles.

  20. Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism

    Directory of Open Access Journals (Sweden)

    Shaan S. Naughton

    2013-01-01

    Full Text Available Endocannabinoids and their G-protein coupled receptors (GPCR are a current research focus in the area of obesity due to the system’s role in food intake and glucose and lipid metabolism. Importantly, overweight and obese individuals often have higher circulating levels of the arachidonic acid-derived endocannabinoids anandamide (AEA and 2-arachidonoyl glycerol (2-AG and an altered pattern of receptor expression. Consequently, this leads to an increase in orexigenic stimuli, changes in fatty acid synthesis, insulin sensitivity, and glucose utilisation, with preferential energy storage in adipose tissue. As endocannabinoids are products of dietary fats, modification of dietary intake may modulate their levels, with eicosapentaenoic and docosahexaenoic acid based endocannabinoids being able to displace arachidonic acid from cell membranes, reducing AEA and 2-AG production. Similarly, oleoyl ethanolamide, a product of oleic acid, induces satiety, decreases circulating fatty acid concentrations, increases the capacity for β-oxidation, and is capable of inhibiting the action of AEA and 2-AG in adipose tissue. Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain.

  1. Efficient fermentation of xylose to ethanol at high formic acid concentrations by metabolically engineered Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Hasunuma, Tomohisa; Yoshimura, Kazuya; Matsuda, Fumio [Kobe Univ., Hyogo (Japan). Organization of Advanced Science and Technology; Sung, Kyung-mo; Sanda, Tomoya; Kondo, Akihiko [Kobe Univ., Hyogo (Japan). Dept. of Chemical Science and Engineering

    2011-05-15

    Recombinant yeast strains highly tolerant to formic acid during xylose fermentation were constructed. Microarray analysis of xylose-fermenting Saccharomyces cerevisiae strain overexpressing endogenous xylulokinase in addition to xylose reductase and xylitol dehydrogenase from Pichia stipitis revealed that upregulation of formate dehydrogenase genes (FDH1 and FDH2) was one of the most prominent transcriptional events against excess formic acid. The quantification of formic acid in medium indicated that the innate activity of FDH was too weak to detoxify formic acid. To reinforce the capability for formic acid breakdown, the FDH1 gene was additionally overexpressed in the xylose-metabolizing recombinant yeast. This modification allowed the yeast to rapidly decompose excess formic acid. The yield and final ethanol concentration in the presence of 20 mM formic acid is as essentially same as that of control. The fermentation profile also indicated that the production of xylitol and glycerol, major by-products in xylose fermentation, was not affected by the upregulation of FDH activity. (orig.)

  2. Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.

    Science.gov (United States)

    van der Sluis, Rencia; Erasmus, Elardus

    2016-10-01

    Activation of fatty acids by the acyl-CoA synthetases (ACSs) is the vital first step in fatty acid metabolism. The enzymatic and physiological characterization of the human xenobiotic/medium chain fatty acid: CoA ligases (ACSMs) has been severely neglected even though xenobiotics, such as benzoate and salicylate, are detoxified through this pathway. This review will focus on the nomenclature and substrate specificity of the human ACSM ligases; the biochemical and enzymatic characterization of ACSM1 and ACSM2B; the high sequence homology of the ACSM2 genes (ACSM2A and ACSM2B) as well as what is currently known regarding disease association studies. Several discrepancies exist in the current literature that should be taken note of. For example, the single nucleotide polymorphisms (SNPs) reported to be associated with aspirin metabolism and multiple risk factors of metabolic syndrome are incorrect. Kinetic data on the substrate specificity of the human ACSM ligases are non-existent and currently no data exist on the influence of SNPs on the enzyme activity of these ligases. One of the biggest obstacles currently in the field is that glycine conjugation is continuously studied as a one-step process, which means that key regulatory factors of the two individual steps remain unknown.

  3. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yang [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100080 (China); Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Dai Jiayin [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China)], E-mail: daijy@ioz.ac.cn

    2008-09-29

    The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 {mu}g PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor {alpha} (PPAR{alpha}), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6

  4. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    International Nuclear Information System (INIS)

    Liu Yang; Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi; Dai Jiayin

    2008-01-01

    The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 μg PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor α (PPARα), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These

  5. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  6. Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

  7. Ruminal fatty acid metabolism : altering rumen biohydrolgenation to improve milk fatty acid profile of dairy cows

    NARCIS (Netherlands)

    Sterk, A.R.

    2011-01-01

    Nutritional guidelines promote a reduced intake of saturated fatty acids (FA) and increased intake of unsaturated FA by humans. Milk and dairy products contain a high proportion of saturated FA caused by extensive alterations of dietary lipids in the rumen through the processes of lipolysis and

  8. Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis.

    Science.gov (United States)

    Mohamed, T; Oikawa, S; Iwasaki, Y; Mizunuma, Y; Takehana, K; Endoh, D; Kurosawa, T; Sato, H

    2004-04-01

    This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.

  9. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

    Science.gov (United States)

    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  10. Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases.

    Science.gov (United States)

    Halilbasic, Emina; Steinacher, Daniel; Trauner, Michael

    2017-01-01

    Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on "Bile Acids in Health and Disease" held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC. © 2017 S. Karger AG, Basel.

  11. Potential of nor-Ursodeoxycholic Acid in Cholestatic and Metabolic Disorders.

    Science.gov (United States)

    Trauner, Michael; Halilbasic, Emina; Claudel, Thierry; Steinacher, Daniel; Fuchs, Claudia; Moustafa, Tarek; Pollheimer, Marion; Krones, Elisabeth; Kienbacher, Christian; Traussnigg, Stefan; Kazemi-Shirazi, Lili; Munda, Petra; Hofer, Harald; Fickert, Peter; Paumgartner, Gustav

    2015-01-01

    24-nor-ursodeoxycholic acid (norUDCA) is a side-chain shortened derivate of ursodeoxycholic acid (UDCA). Since norUDCA is only ineffectively conjugated with glycine or taurine, it has specific physicochemical and therapeutic properties distinct from UDCA. Nonamidated norUDCA undergoes cholehepatic shunting enabling 'ductular targeting' and inducing a bicarbonate-rich hypercholeresis, with cholangioprotective effects. At the same time it has direct anti-inflammatory, antilipotoxic, anti fibrotic, and antiproliferative properties targeting various liver cell populations. norUDCA appears to be one of the most promising novel treatment approaches targeting the liver and the bile duct system at multifactorial and multicellular levels. This review article is a summary of a lecture given at the XXIII International Bile Acid Meeting (Falk Symposium 194) on 'Bile Acids as Signal Integrators and Metabolic Modulators' held in Freiburg, October 8-9, 2014, and summarizes the recent progress with norUDCA as a novel therapeutic approach in cholestatic and metabolic (liver) disorders. 2015 S. Karger AG, Basel.

  12. Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy.

    Science.gov (United States)

    Grzes, K M; Swamy, M; Hukelmann, J L; Emslie, E; Sinclair, L V; Cantrell, D A

    2017-12-01

    This study explores the regulation and importance of System L amino acid transport in a murine model of T-cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P 3 ) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1α or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the predominant amino acid transporter in primary PTEN -/- T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data reveal the importance of regulated amino acid transport for T-cell malignancies, highlighting how a single amino acid transporter can have a key role.

  13. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    Science.gov (United States)

    Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

    2012-01-01

    A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. Copyright © 2012. Published by Elsevier Inc.

  14. The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals

    Directory of Open Access Journals (Sweden)

    Anastasia V. Shindyapina

    2017-12-01

    Full Text Available The healthy human body contains small amounts of metabolic formaldehyde (FA that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and in the gastrointestinal microbiome. With age, the ability to maintain a low level of FA decreases, which increases the risk of Alzheimer's disease and dementia. It has been shown that 1,2-dithiolane-3-pentanoic acid or alpha lipoic acid (ALA, a naturally occurring dithiol and antioxidant cofactor of mitochondrial α-ketoacid dehydrogenases, increases glutathione (GSH content and FA metabolism by mitochondrial aldehyde dehydrogenase 2 (ALDH2 thus manifests a therapeutic potential beyond its antioxidant property. We suggested that ALA can contribute to a decrease in the FA content of mammals by acting on ALDH2 expression. To test this assumption, we administered ALA in mice in order to examine the effect on FA metabolism and collected blood samples for the measurement of FA. Our data revealed that ALA efficiently eliminated FA in mice. Without affecting the specific activity of FA-metabolizing enzymes (ADH1, ALDH2, and ADH5, ALA increased the GSH content in the brain and up-regulated the expression of the FA-metabolizing ALDH2 gene in the brain, particularly in the hippocampus, but did not impact its expression in the liver in vivo or in rat liver isolated from the rest of the body. After ALA administration in mice and in accordance with the increased content of brain ALDH2 mRNA, we detected increased ALDH2 activity in brain homogenates. We hypothesized that the beneficial effects of ALA on patients with Alzheimer's disease may be associated with accelerated ALDH2-mediated FA detoxification and clearance.

  15. Valproic acid promotes neuronal differentiation by induction of proneural factors in association with H4 acetylation.

    Science.gov (United States)

    Yu, In Tag; Park, Jin-Yong; Kim, Sung Hyun; Lee, Jeong-Sik; Kim, Yong-Seok; Son, Hyeon

    2009-02-01

    Valproate (VPA) influences the proliferation and differentiation of neuronal cells. However, little is known about the downstream events, such as alterations in gene transcription, that are associated with cell fate choice. To determine whether VPA plays an instructive role in cell fate choice during hippocampal neurogenesis, the expression of genes involved in the cell cycle and neuronal differentiation was investigated. Treatment with VPA during the progenitor stages resulted in strong inhibition of cell proliferation and induction of neuronal differentiation, accompanied by increases in the expression of proneural transcription factors and in neuronal cell numbers. The increased expression of Ngn1, Math1 and p15 points to a shift towards neuronal fate in response to histone deacetylase inhibitors (HDACi). Chromatin immunoprecipitation (ChIP) analysis showed that acetylated histone H4 (Ac-H4) was associated with the Ngn1, Math1 and p15 promoters in cultured hippocampal neural progenitor cells. VPA-induced hippocampal neurogenesis was also accompanied by association of Ac-H4 with the Ngn1 promoter in hippocampal extracts. The discovery of an association between HDACi and the Ngn1, Math1 and p15 promoters extends the importance of HDAC inhibition as a key regulator of neuronal differentiation at the transcriptional level.

  16. Carbon Source-Dependent Inducible Metabolism of Veratryl Alcohol and Ferulic Acid in Pseudomonas putida CSV86

    Science.gov (United States)

    Mohan, Karishma

    2017-01-01

    ABSTRACT Pseudomonas putida CSV86 degrades lignin-derived metabolic intermediates, viz., veratryl alcohol, ferulic acid, vanillin, and vanillic acid, as the sole sources of carbon and energy. Strain CSV86 also degraded lignin sulfonate. Cell respiration, enzyme activity, biotransformation, and high-pressure liquid chromatography (HPLC) analyses suggest that veratryl alcohol and ferulic acid are metabolized to vanillic acid by two distinct carbon source-dependent inducible pathways. Vanillic acid was further metabolized to protocatechuic acid and entered the central carbon pathway via the β-ketoadipate route after ortho ring cleavage. Genes encoding putative enzymes involved in the degradation were found to be present at fer, ver, and van loci. The transcriptional analysis suggests a carbon source-dependent cotranscription of these loci, substantiating the metabolic studies. Biochemical and quantitative real-time (qRT)-PCR studies revealed the presence of two distinct O-demethylases, viz., VerAB and VanAB, involved in the oxidative demethylation of veratric acid and vanillic acid, respectively. This report describes the various steps involved in metabolizing lignin-derived aromatic compounds at the biochemical level and identifies the genes involved in degrading veratric acid and the arrangement of phenylpropanoid metabolic genes as three distinct inducible transcription units/operons. This study provides insight into the bacterial degradation of lignin-derived aromatics and the potential of P. putida CSV86 as a suitable candidate for producing valuable products. IMPORTANCE Pseudomonas putida CSV86 metabolizes lignin and its metabolic intermediates as a carbon source. Strain CSV86 displays a unique property of preferential utilization of aromatics, including for phenylpropanoids over glucose. This report unravels veratryl alcohol metabolism and genes encoding veratric acid O-demethylase, hitherto unknown in pseudomonads, thereby providing new insight into the

  17. Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Saltin, B; Wagenmakers, A J

    1999-01-01

    to a substantial increase in net muscle protein degradation, and that a lowering of the starting muscle glycogen content leads to a further increase. The carbon atoms of the branched-chain amino acids (BCAA), glutamate, aspartate and asparagine, liberated by protein degradation, and the BCAA and glutamate......The aim of this study was to investigate whether prolonged one-leg knee-extensor exercise enhances net protein degradation in muscle with a normal or low glycogen content. Net amino acid production, as a measure of net protein degradation, was estimated from leg exchange and from changes...... in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60...

  18. Interrelationship of dietary lipids and ascorbic acid with hepatic enzymes of cholesterol metabolic pathway.

    Science.gov (United States)

    Sen, S; Mukherjee, S

    1997-01-01

    Effect of unsaturated and saturated fats on cholesterol metabolism was studied in ascorbate sufficient and deficient guineapigs. Experimental animals were made chronic ascorbic acid deficient by allowing oral intake of 0.5 mg ascorbic acid/day/animal. Elevation in serum and liver cholesterol and triglyceride along with depression in cholesterol oxidation and 7 alpha-hydroxylation in liver was observed in unsaturated fat fed guineapigs with ascorbate deficiency. Liver microsomal cytochrome P-450 level was found to be low in ascorbate deficient animals. Polyunsaturated fat intake could not lower the serum cholesterol level in ascorbate deficiency. Today polyunsaturated fat in the diet is encouraged all over the world for its hypocholesterolemic effect. This study indicates that polyunsaturated fat intake with ascorbic acid deficiency may produce hypercholesterolemia.

  19. Co-metabolic formation of substituted phenylacetic acids by styrene-degrading bacteria

    Directory of Open Access Journals (Sweden)

    Michel Oelschlägel

    2015-06-01

    The styrene-degrading strains Rhodococcus opacus 1CP, Pseudomonas fluorescens ST, and the novel isolates Sphingopyxis sp. Kp5.2 and Gordonia sp. CWB2 were investigated with respect to their applicability to co-metabolically produce substituted phenylacetic acids. Isolates were found to differ significantly in substrate tolerance and biotransformation yields. Especially, P. fluorescens ST was identified as a promising candidate for the production of several phenylacetic acids. The biotransformation of 4-chlorostyrene with cells of strain ST was shown to be stable over a period of more than 200 days and yielded about 38 mmolproduct gcelldryweight−1 after nearly 350 days. Moreover, 4-chloro-α-methylstyrene was predominantly converted to the (S-enantiomer of the acid with 40% enantiomeric excess.

  20. Reconstituted high-density lipoprotein infusion modulates fatty acid metabolism in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Drew, BG; Carey, AL; Natoli, AK

    2011-01-01

    We recently demonstrated that reconstituted high-density lipoprotein (rHDL) modulates glucose metabolism in humans via both AMP-activated protein kinase (AMPK) in muscle and by increasing plasma insulin. Given the key roles of both AMPK and insulin in fatty acid metabolism, the current study inve...

  1. 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 ...

  2. Serum uric acid concentration and metabolic syndrome among elderly Koreans: The Korean Urban Rural Elderly (KURE) study.

    Science.gov (United States)

    Choi, Hansol; Kim, Hyeon Chang; Song, Bo Mi; Park, Ji Hye; Lee, Ju-Mi; Yoon, Da-Lim; Yoon, Young Mi; Rhee, Yumie; Youm, Yousik; Kim, Chang Oh

    2016-01-01

    Epidemiologic studies have demonstrated that elevated serum uric acid concentration is an independent risk factor for metabolic syndrome. However, few studies have focused on elderly populations. Thus, we investigated the association of serum uric acid concentration with metabolic syndrome in community-dwelling elderly Koreans. This cross-sectional analysis included 2940 participants (986 men and 1954 women) aged 65 years or older who participated in a baseline health assessment for the Korean Urban Rural Elderly cohort study from 2012 to 2014. Serum uric acid concentration was analyzed using both continuous and dichotomous variables. Hyperuricemia was defined as a uric acid concentration ≥7.0 mg/dL in men and ≥6.0 mg/dL in women. Metabolic syndrome was defined according to the 2009 harmonizing definition. Multiple logistic regression models were used to investigate independent association between serum uric acid and metabolic syndrome, after adjusting for age, body mass index, LDL cholesterol, glycated hemoglobin, blood urea nitrogen, estimated glomerular filtration rate health behaviors, and medications. Prevalence of metabolic syndrome and its components increased significantly according to uric acid concentration in both sexes. The adjusted odds ratios for having metabolic syndrome per 1.0mg/dL higher uric acid concentration were 1.16 (95% CI: 1.03-1.31) in men and 1.27 (95% CI: 1.13-1.42) in women. Hyperuricemia was also associated with metabolic syndrome, with adjusted odds ratios of 1.71 (95% CI: 1.11-2.63) in men and 1.55 (95% CI: 1.05-2.29) in women. Elevated serum uric acid concentration was independently associated with an increased prevalence of metabolic syndrome in community-dwelling elderly Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. 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...

  4. Free amino acid content and metabolic activities of setting and aborting soybean ovaries

    International Nuclear Information System (INIS)

    Ghiasi, H.; Paech, C.; Dybing, C.D.

    1987-01-01

    Fruits of soybean (glycine max [L.] Merr.) that are destined to abscise shortly after anthesis grow more slowly than fruits that will be retained. In this work, amino acid composition, protein metabolism, and nucleic acid metabolism were studied in setting and abscising soybean ovaries from anthesis to 6 days after anthesis. Principal free amino acids were asparagine, aspartic acid, glutamic acid, serine, and glutamine. Percent aspartate and glutamate declined as the ovaries grew, with aspartate declining more in abscising and glutamate more in setting ovaries. Percent glutamate was positively correlated to percent abscission throughout the period. Proline, serine, and leucine were positively correlated to abscission from 0 to 2 days after anthesis, whereas significant negative correlations were observed at these ages for ethanolamine and arginine. 75 Se fed as selenate and 14 C fed as sucrose, glycine, and alanine were readily incorporated into soluble and insoluble proteins in a 24-hour in vitro incubation. Radioactivity of total proteins, expressed on a per-ovary basis, was negatively correlated with percent abscission and positively correlated with ovary weight. [ 14 C]Glutamine and serine followed the opposite pattern, with greater protein labeling in abscising than in setting ovaries. When data were expressed as disintegrations per minute per milligram ovary fresh weight, protein labeling from alanine was seen to be significantly greater in abscising ovaries at anthesis and throughout the sampling period. Nucleic acid labeling from uridine was highly correlated to ovary weight; labeling from thymidine was greater in setting than abscising ovaries at anthesis and in abscising ovaries at later stages of development

  5. Effects of volatile fatty acids on propionate metabolism and gluconeogenesis in caprine hepatocytes

    International Nuclear Information System (INIS)

    Aiello, R.J.; Armentano, L.E.

    1987-01-01

    Isolated caprine hepatocytes were incubated with fatty acids of various chain lengths. Short-chain fatty acids effects on rates of gluconeogenesis and oxidation from [2- 14 C] propionate were determined. Additions of glucose (2.5 mM) had no effect on hepatic [2- 14 C]-propionate metabolism in the presence and absence of amino acids. A complete mixture of amino acids increased label incorporation from [2- 14 C] propionate into [ 14 C] glucose by 22%. Butyrate inhibited [2- 14 C] propionate metabolism and increased the apparent Michaelis constant for [2- 14 C] propionate incorporation into [ 14 C] glucose from 2.4 +/- 1.5 to 5.6 +/- .9 mM. Butyrate's effects on propionate were similar in the presence and absence of L-carnitine (1 mM). Isobutyrate, 2-methylbutyrate, and valerate (1.25 mM) had no effect on [ 14 C] glucose production but decreased 14 CO 2 production to 57, 61, and 54% of the control [2- 14 C] propionate (1.25 mM). This inhibition on 14 CO 2 was not competitive. Isovalerate had no effect on either [2- 14 C] propionate incorporation into glucose of CO 2 . An increase in ratio of [ 14 C] glucose to 14 CO 2 from [2- 14 C]-propionate demonstrated that short-chain fatty acids other than butyrate do not inhibit gluconeogenesis from propionate. In addition, fatty acids that generate a net synthesis of intracellular oxaloacetate may partition propionate carbons toward gluconeogenic rather than oxidative pathways in goat hepatocytes

  6. Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-07-01

    Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

  7. Synthesis of a metabolically stable modified long-chain fatty acid salt and its photolabile derivative

    Energy Technology Data Exchange (ETDEWEB)

    Stoll, G.H.; Voges, R.; Gerok, W.; Kurz, G. (Institut fuer Organische Chemie and Biochemie, Universitaet Freiburg (Germany))

    1991-05-01

    An analogue of the long-chain fatty acid salt, sodium stearate, was synthesized in which the hydrogen atoms at carbons 2, 3, and 18 were replaced by fluorine. The key step in the synthesis was the addition of 3-iodo-2,2,3,3-tetrafluoropropanoic acid amide to 15,15,15-trifluoro-1-pentadecene. Radioactivity was introduced by catalytic reduction of 2,2,3,3,18,18,18-heptafluoro-4-octadecenoic acid amide with carrier-free tritium gas yielding a product with the specific radioactivity of 2.63 TBq/mmol. The resulting 2,2,3,3,18,18,18-heptafluoro-4-octadecenoic acid has a pKa of about 0.5 and is completely dissociated under normal physiological conditions. The fluorinated fatty acid salt analogue is readily taken up into hepatocytes and proved to be metabolically inert. In an approach to the identification of proteins involved in long-chain fatty acid salt transport across membranes and intracellular compartments, the photolabile derivative 11,11-azo-2,2,3,3,18,18,18-heptafluoro(G-3H)octadecanoic acid sodium salt was synthesized with a specific radioactivity of 2.63 TBq/mmol. Photolysis of the photolabile derivative, using a light source with a maximum emission at 350 nm, occurred with a half-life of 1.5 min. The generated carbene reacted with 14C-labeled methanol and acetonitrile with covalent bond formation of 6-13%. Its efficacy for photoaffinity labeling was demonstrated by incorporation into serum albumin, the extracellular fatty acid salt-binding protein, as well as into the intracellular fatty acid salt-binding protein (FABP) of rat liver with the molecular weight of 14,000.

  8. Genetic and metabolic engineering for microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Cao, Mingfeng; Feng, Jun; Sirisansaneeyakul, Sarote; Song, Cunjiang; Chisti, Yusuf

    2018-05-28

    Poly-γ-glutamic acid (γ-PGA) is a natural biopolymer of glutamic acid. The repeating units of γ-PGA may be derived exclusively from d-glutamic acid, or l-glutamic acid, or both. The monomer units are linked by amide bonds between the α-amino group and the γ-carboxylic acid group. γ-PGA is biodegradable, edible and water-soluble. It has numerous existing and emerging applications in processing of foods, medicines and cosmetics. This review focuses on microbial production of γ-PGA via genetically and metabolically engineered recombinant bacteria. Strategies for improving production of γ-PGA include modification of its biosynthesis pathway, enhancing the production of its precursor (glutamic acid), and preventing loss of the precursor to competing byproducts. These and other strategies are discussed. Heterologous synthesis of γ-PGA in industrial bacterial hosts that do not naturally produce γ-PGA is discussed. Emerging trends and the challenges affecting the production of γ-PGA are reviewed. Copyright © 2018. Published by Elsevier Inc.

  9. Effect of fatty acid interaction on myoglobin oxygen affinity and triglyceride metabolism.

    Science.gov (United States)

    Jue, Thomas; Simond, Gregory; Wright, Traver J; Shih, Lifan; Chung, Youngran; Sriram, Renuka; Kreutzer, Ulrike; Davis, Randall W

    2016-08-01

    Recent studies have suggested myoglobin (Mb) may have other cellular functions in addition to storing and transporting O 2 . Indeed, NMR experiments have shown that the saturated fatty acid (FA) palmitate (PA) can interact with myoglobin (Mb) in its ligated state (MbCO and MbCN) but does not interact with Mb in its deoxygenated state. The observation has led to the hypothesis that Mb can also serve as a fatty acid transporter. The present study further investigates fatty acid interaction with the physiological states of Mb using the more soluble but unsaturated fatty acid, oleic acid (OA). OA binds to MbCO but does not bind to deoxy Mb. OA binding to Mb, however, does not alter its O 2 affinity. Without any Mb, muscle has a significantly lower level of triglyceride (TG). In Mb knock-out (MbKO) mice, both heart and skeletal muscles have lower level of TG relative to the control mice. Training further decreases the relative TG in the MbKO skeletal muscle. Nevertheless, the absence of Mb and lower TG level in muscle does not impair the MbKO mouse performance as evidenced by voluntary wheel running measurements. The results support the hypothesis of a complex physiological role for Mb, especially with respect to fatty acid metabolism.

  10. Simultaneous induction of jasmonic acid and disease-responsive genes signifies tolerance of American elm to Dutch elm disease

    Science.gov (United States)

    Sherif , S. M.; Shukla, M. R.; Murch, S. J.; Bernier, L.; Saxena, P. K.

    2016-01-01

    Dutch elm disease (DED), caused by three fungal species in the genus Ophiostoma, is the most devastating disease of both native European and North American elm trees. Although many tolerant cultivars have been identified and released, the tolerance mechanisms are not well understood and true resistance has not yet been achieved. Here we show that the expression of disease-responsive genes in reactions leading to tolerance or susceptibility is significantly differentiated within the first 144 hours post-inoculation (hpi). Analysis of the levels of endogenous plant defense molecules such as jasmonic acid (JA) and salicylic acid (SA) in tolerant and susceptible American elm saplings suggested SA and methyl-jasmonate as potential defense response elicitors, which was further confirmed by field observations. However, the tolerant phenotype can be best characterized by a concurrent induction of JA and disease-responsive genes at 96 hpi. Molecular investigations indicated that the expression of fungal genes (i.e. cerato ulmin) was also modulated by endogenous SA and JA and this response was unique among aggressive and non-aggressive fungal strains. The present study not only provides better understanding of tolerance mechanisms to DED, but also represents a first, verified template for examining simultaneous transcriptomic changes during American elm-fungus interactions. PMID:26902398

  11. Induction of Shikimic Acid Pathway Enzymes by Light in Suspension Cultured Cells of Parsley (Petroselinum crispum) 1

    Science.gov (United States)

    McCue, Kent F.; Conn, Eric E.

    1990-01-01

    Light treatment of suspension cultured cells of parsley (Petroselinum crispum) was shown to increase the activity of the shikimic acid pathway enzyme, 3-deoxy-d-arabino-heptulosonic acid-7-phosphate (DAHP) synthase (EC 4.1.2.15). DAHP synthase activity was assayed for two isoforms, DS-Mn and DS-Co (RJ Ganson, TA d'Amato, RA Jensen [1986] Plant Physiol 82: 203-210). Light increased the enzymatic activity of the plastidic isoform DS-Mn as much as 2-fold, averaging 1.6-fold with >95% confidence. The cytosolic isoform DS-Co was unaffected. Cycloheximide and actinomycin D, translational and transcriptional inhibitors, respectively, both reversed induction of DS-Mn by light suggesting transcriptional regulation of the gene. Chorismate mutase activity was assayed for the two isoforms CM I and CM II (BK Singh, JA Connelly, EE Conn [1985] Arch Biochem Biophys 243: 374-384). Treatment by light did not significantly affect either chorismate mutase isoform. The ratio of the two chorismate mutase isoforms changed during the growth cycle, with an increase in the ratio of plastidic to cytosolic isoforms occurring towards the end of logarithmic growth. PMID:16667741

  12. Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

    Directory of Open Access Journals (Sweden)

    Pelletier Eric

    2010-10-01

    Full Text Available Abstract Background Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed. Results C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms. Conclusions Analysis of the C

  13. Transcriptome and Proteome Expression Analysis of the Metabolism of Amino Acids by the Fungus Aspergillus oryzae in Fermented Soy Sauce

    Directory of Open Access Journals (Sweden)

    Guozhong Zhao

    2015-01-01

    Full Text Available Amino acids comprise the majority of the flavor compounds in soy sauce. A portion of these amino acids are formed from the biosynthesis and metabolism of the fungus Aspergillus oryzae; however, the metabolic pathways leading to the formation of these amino acids in A. oryzae remain largely unknown. We sequenced the transcriptomes of A. oryzae 100-8 and A. oryzae 3.042 under similar soy sauce fermentation conditions. 2D gel electrophoresis was also used to find some differences in protein expression. We found that many amino acid hydrolases (endopeptidases, aminopeptidases, and X-pro-dipeptidyl aminopeptidase were expressed at much higher levels (mostly greater than double in A. oryzae 100-8 than in A. oryzae 3.042. Our results indicated that glutamate dehydrogenase may activate the metabolism of amino acids. We also found that the expression levels of some genes changed simultaneously in the metabolic pathways of tyrosine and leucine and that these conserved genes may modulate the function of the metabolic pathway. Such variation in the metabolic pathways of amino acids is important as it can significantly alter the flavor of fermented soy sauce.

  14. Transcriptome and Proteome Expression Analysis of the Metabolism of Amino Acids by the Fungus Aspergillus oryzae in Fermented Soy Sauce.

    Science.gov (United States)

    Zhao, Guozhong; Yao, Yunping; Wang, Chunling; Tian, Fengwei; Liu, Xiaoming; Hou, Lihua; Yang, Zhen; Zhao, Jianxin; Zhang, Hao; Cao, Xiaohong

    2015-01-01

    Amino acids comprise the majority of the flavor compounds in soy sauce. A portion of these amino acids are formed from the biosynthesis and metabolism of the fungus Aspergillus oryzae; however, the metabolic pathways leading to the formation of these amino acids in A. oryzae remain largely unknown. We sequenced the transcriptomes of A. oryzae 100-8 and A. oryzae 3.042 under similar soy sauce fermentation conditions. 2D gel electrophoresis was also used to find some differences in protein expression. We found that many amino acid hydrolases (endopeptidases, aminopeptidases, and X-pro-dipeptidyl aminopeptidase) were expressed at much higher levels (mostly greater than double) in A. oryzae 100-8 than in A. oryzae 3.042. Our results indicated that glutamate dehydrogenase may activate the metabolism of amino acids. We also found that the expression levels of some genes changed simultaneously in the metabolic pathways of tyrosine and leucine and that these conserved genes may modulate the function of the metabolic pathway. Such variation in the metabolic pathways of amino acids is important as it can significantly alter the flavor of fermented soy sauce.

  15. 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.

  16. 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.

  17. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  18. Alterations in fatty acid metabolism in response to obesity surgery combined with dietary counseling.

    Science.gov (United States)

    Walle, P; Takkunen, M; Männistö, V; Vaittinen, M; Käkelä, P; Ågren, J; Schwab, U; Lindström, J; Tuomilehto, J; Uusitupa, M; Pihlajamäki, J

    2017-09-04

    The effects of obesity surgery on serum and adipose tissue fatty acid (FA) profile and FA metabolism may modify the risk of obesity-related diseases. We measured serum (n=122) and adipose tissue (n=24) FA composition and adipose tissue mRNA expression of genes regulating FA metabolism (n=100) in participants of the Kuopio Obesity Surgery Study (KOBS, age 47.2±8.7 years, BMI 44.6±6.0, 40 men, 82 women) before and one year after obesity surgery. As part of the surgery protocol, all the subjects were instructed to add sources of unsaturated fatty acids, such as rapeseed oil and fatty fish, into their diet. The results were compared with changes in serum FA composition in 122 subjects from the Finnish Diabetes Prevention study (DPS) (age 54.3±7.1 years, BMI 32.2±4.6, 28 men, 94 women). The proportion of saturated FAs decreased and the proportion of n-3 and n-6 FAs increased in serum triglycerides after obesity surgery (all Pobesity surgery in all lipid fractions (all Pobesity surgery and lifestyle intervention, except for the change in the absolute amounts of n-3 FAs between the two studies (P=0.044). Beneficial changes in serum and adipose tissue FAs after obesity surgery could be associated with changes in endogenous metabolism and diet.

  19. Effect of oxygen deprivation on metabolism of arachidonic acid by cultures of rat heart cells

    International Nuclear Information System (INIS)

    Freyss-Beguin, M.; Millanvoye-van Brussel, E.; Duval, D.

    1989-01-01

    To investigate the mechanisms responsible for the impairment of phospholipid metabolism observed in ischemic cells, we have studied the effect of conditions simulating ischemia on the metabolism of arachidonic acid (AA) by muscle (M-) and nonmuscle (F-) cells isolated from newborn rat hearts and cultured separately. In muscle cells, oxygen deprivation induces a significant stimulation of the release of [ 14 C]AA from prelabeled cells associated with a preferential redistribution of [ 14 C]AA into cell triglycerides but not formation of radioactive prostaglandins. Moreover, the fatty acid content of phospholipids, as measured by capillary gas chromatography, appears markedly reduced in ischemic myocardial cells. This fact may be related to phospholipase stimulation during ischemia as suggested by the antagonistic effect of mepacrine or p-bromophenacyl bromide. In contrast, oxygen deprivation failed to induce any significant alteration of AA metabolism in fibroblast-like heart cells. Our results indicate that these cultures of newborn rat heart cells, which exhibit many of the features observed in intact organ during ischemia, may represent a useful experimental model to investigate the pharmacological control of the membrane phospholipid turnover

  20. Polarity of fatty acid uptake and metabolism in a human intestinal cell line (CACO-2)

    International Nuclear Information System (INIS)

    Trotter, P.J.; Storch, J.

    1990-01-01

    Free fatty acids (ffa) can enter the intestinal cell via the apical (AP) or basolateral (BL) membrane. The authors are using the Caco-2 intestinal cell line to examine the polarity of ffa uptake and metabolism in the enterocyte. Cells are grown on permeable polycarbonate Transwell filters in order to obtain access to both AP and BL compartments. Differentiated Caco-2 cells form tight polarized monolayers which express small intestine-specific enzymes and are impermeable to the fluid phase marker Lucifer Yellow. Submicellar concentrations of 3 H-palmitic acid (2uM) were added to AP or BL sides of Caco-2 monolayers at 37 degrees C and cells were incubated for various times between 2 and 120 minutes. Total AP and BL uptake is similar; however, when relative membrane surface areas are accounted for, AP uptake is about 2-fold higher. The metabolism of AP and BL ffa is not significantly different: triacylglycerol and phosphatidylcholine account for most of the metabolites (32±4 and 24±2% respectively at 5 minutes). Little ffa oxidation is observed. Preincubation with albumin-bound 2-monoolein (100uM) and palmitate (50uM) increases the level of TG metabolites. The results suggest that in this cell line the uptake of AP ffa may be greater than BL ffa, but that AP (dietary) ffa and BL (plasma) ffa are metabolized similarly

  1. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

    Science.gov (United States)

    Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

  2. Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase.

    Science.gov (United States)

    Bakke, Siril S; Moro, Cedric; Nikolić, Nataša; Hessvik, Nina P; Badin, Pierre-Marie; Lauvhaug, Line; Fredriksson, Katarina; Hesselink, Matthijs K C; Boekschoten, Mark V; Kersten, Sander; Gaster, Michael; Thoresen, G Hege; Rustan, Arild C

    2012-10-01

    Development of insulin resistance is positively associated with dietary saturated fatty acids and negatively associated with monounsaturated fatty acids. To clarify aspects of this difference we have compared the metabolism of oleic (OA, monounsaturated) and palmitic acids (PA, saturated) in human myotubes. Human myotubes were treated with 100μM OA or PA and the metabolism of [(14)C]-labeled fatty acid was studied. We observed that PA had a lower lipolysis rate than OA, despite a more than two-fold higher protein level of adipose triglyceride lipase after 24h incubation with PA. PA was less incorporated into triacylglycerol and more incorporated into phospholipids after 24h. Supporting this, incubation with compounds modifying lipolysis and reesterification pathways suggested a less influenced PA than OA metabolism. In addition, PA showed a lower accumulation than OA, though PA was oxidized to a relatively higher extent than OA. Gene set enrichment analysis revealed that 24h of PA treatment upregulated lipogenesis and fatty acid β-oxidation and downregulated oxidative phosphorylation compared to OA. The differences in lipid accumulation and lipolysis between OA and PA were eliminated in combination with eicosapentaenoic acid (polyunsaturated fatty acid). In conclusion, this study reveals that the two most abundant fatty acids in our diet are partitioned toward different metabolic pathways in muscle cells, and this may be relevant to understand the link between dietary fat and skeletal muscle insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. RETINOIC ACID INDUCTION OF CLEFT PALATE IN EGF AND TGF-ALPHA KNOCKOUT MICE: STAGE SPECIFIC INFLUENCES OF GROWTH FACTOR EXPRESSION

    Science.gov (United States)

    ABBOTT, B. D., LEFFLER, K.E. AND BUCKALEW, A.R, Reproductive Toxicology Division, NHEERL, ORD, US EPA, Research Triangle Park, North Carolina. Retinoic acid induction of cleft palate (CP) in EGF and TGF knockout mice: Stage specific influences of growth factor expression.<...

  4. Wavelength-dependent induction of UV absorbing mycosporine-like amino acids in the red alga Chondrus crispus under natural solar radiation

    NARCIS (Netherlands)

    Krabs, G; Bischof, K; Hanelt, D; Karsten, U; Wiencke, C

    2002-01-01

    Polychromatic response spectra for the induction of UV absorbing mycosporine-like amino acids (MAAs) were calculated after exposing small thalli of the red alga Chondrus crispus under various cut-off filters to natural solar radiation on the North Sea island Helgoland, Germany. The laboratory-gr