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Sample records for amino metabolism modifications

  1. Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

    OpenAIRE

    Pujos-Guillot, Estelle; Pickering, Gisèle; Lyan, Bernard; Ducheix, Gilles; Brandolini-Bunlon, Marion; Glomot, Françoise; Dardevet, Dominique; Dubray, Claude; PAPET, Isabelle

    2011-01-01

    Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on ...

  2. 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. To....... Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice....

  3. 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...... 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, these...

  4. Amino acid modifications on tRNA

    Institute of Scientific and Technical Information of China (English)

    Jing Yuan; Kelly Sheppard; Dieter S(o)ll

    2008-01-01

    The accurate formation of cognate aminoacyl-transfer RNAs (aa-tRNAs) is essential for the fidelity of translation.Most amino acids are esterified onto their cognate tRNA isoacceptors directly by aa.tRNA synthetases.However,in the case of four amino acids (Gin,Asn,Cys and Sec),aminoacyl-tRNAs are made through indirect pathways in many organisms across all three domains of life.The process begins with the charging ofnoncognate amino acids to tRNAs by a specialized synthetase in the case of Cys-tRNAcys formation or by synthetases with relaxed specificity,such as the non-discriminating glutamyl-tRNA,non-discriminating aspartyl-tRNA and seryl-tRNA synthetases.The resulting misacylated tRNAs are then converted to cognate pairs through transformation of the amino acids on the tRNA,which is catalyzed by a group of tRNA-dependent modifying enzymes,such as tRNA-dependent amidotransferases,Sep-tRNA:Cys-tRNA synthase,O-phosphoseryi-tRNA kinase and Sep-tRNA:Sec-tRNA synthase.The majority of these indirect pathways are widely spread in all domains of life and thought to be part of the evolutionary process.

  5. The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia.

    Science.gov (United States)

    Perkins, W J; Lanier, W L; Karlsson, B R; Milde, J H; Michenfelder, J D

    1989-09-25

    The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic

  6. Computational Methods for Modification of Metabolic Networks

    Directory of Open Access Journals (Sweden)

    Takeyuki Tamura

    2015-01-01

    Full Text Available In metabolic engineering, modification of metabolic networks is an important biotechnology and a challenging computational task. In the metabolic network modification, we should modify metabolic networks by newly adding enzymes or/and knocking-out genes to maximize the biomass production with minimum side-effect. In this mini-review, we briefly review constraint-based formalizations for Minimum Reaction Cut (MRC problem where the minimum set of reactions is deleted so that the target compound becomes non-producible from the view point of the flux balance analysis (FBA, elementary mode (EM, and Boolean models. Minimum Reaction Insertion (MRI problem where the minimum set of reactions is added so that the target compound newly becomes producible is also explained with a similar formalization approach. The relation between the accuracy of the models and the risk of overfitting is also discussed.

  7. 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 c

  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. Metabolic Response of Pakchoi Leaves to Amino Acid Nitrogen

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-li; YU Wen-juan; ZHOU Qian; HAN Rui-feng; HUANG Dan-feng

    2014-01-01

    Different nitrogen (N) forms may cause changes in the metabolic profiles of plants. However, few studies have been conducted on the effects of amino acid-N on plant metabolic proifles. The main objective of this study was to identify primary metabolites associated with amino acid-N (Gly, Gln and Ala) through metabolic proifle analysis using gas chromatography-mass spectrometry (GC-MS). Plants of pakchoi (Brassica campestris L. ssp. chinensis L.), Huawang and Wuyueman cultivars, were grown with different nitrogen forms (i.e., Gly, Gln, Ala, NO3--N, and N starvation) applied under sterile hydroponic conditions. The fresh weight and plant N accumulation of Huawang were greater than those of Wuyueman, which indicates that the former exhibited better N-use efficiency than the latter. The physiological performances of the applied N forms were generally in the order of NO3--N>Gln>Gly>Ala. The metabolic analysis of leaf polar extracts revealed 30 amino acid N-responsive metabolites in the two pakchoi cultivars, mainly consisting of sugars, amino acids, and organic acids. Changes in the carbon metabolism of pakchoi leaves under amino acid treatments occurred via the accumulation of fructose, glucose, xylose, and arabinose. Disruption of amino acid metabolism resulted in accumulation of endogenous Gly in Gly treatment, Pro in Ala treatment, and Asn in three amino acid (Gly, Gln and Ala) treatments. By contrast, the levels of endogenous Gln and Leu decreased. However, this reduction varied among cultivars and amino acid types. Amino acid-N supply also affected the citric acid cycle, namely, the second stage of respiration, where leaves in Gly, Gln and Ala treatments contained low levels of malic, citric and succinic acids compared with leaves in NO3--N treatments. No signiifcant difference in the metabolic responses was observed between the two cultivars which differed in their capability to use N. The response of primary metabolites in pakchoi leaves to amino acid-N supply

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

    International Nuclear Information System (INIS)

    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

  11. Role of CCN2 in Amino Acid Metabolism of Chondrocytes.

    Science.gov (United States)

    Murase, Yurika; Hattori, Takako; Aoyama, Eriko; Nishida, Takashi; Maeda-Uematsu, Aya; Kawaki, Harumi; Lyons, Karen M; Sasaki, Akira; Takigawa, Masaharu; Kubota, Satoshi

    2016-04-01

    CCN2/connective tissue growth factor (CTGF) is a multi-functional molecule that promotes harmonized development and regeneration of cartilage through its matricellular interaction with a variety of extracellular biomolecules. Thus, deficiency in CCN2 supply profoundly affects a variety of cellular activities including basic metabolism. A previous study showed that the expression of a number of ribosomal protein genes was markedly enhanced in Ccn2-null chondrocytes. Therefore, in this study, we analyzed the impact of CCN2 on amino acid and protein metabolism in chondrocytes. Comparative metabolome analysis of the amino acids in Ccn2-null and wild-type mouse chondrocytes revealed stable decreases in the cellular levels of all of the essential amino acids. Unexpectedly, uptake of such amino acids was rather enhanced in Ccn2-null chondrocytes, and the addition of exogenous CCN2 to human chondrocytic cells resulted in decreased amino acid uptake. However, as expected, amino acid consumption by protein synthesis was also accelerated in Ccn2-null chondrocytes. Furthermore, we newly found that expression of two genes encoding two glycolytic enzymes, as well as the previously reported Eno1 gene, was repressed in those cells. Considering the impaired glycolysis and retained mitochondrial membrane potential in Ccn2-null chondrocytes, these findings suggest that Ccn2 deficiency induces amino acid shortage in chondrocytes by accelerated amino acid consumption through protein synthesis and acquisition of aerobic energy. Interestingly, CCN2 was found to capture such free amino acids in vitro. Under physiological conditions, CCN2 may be regulating the levels of free amino acids in the extracellular matrix of cartilage. J. Cell. Biochem. 117: 927-937, 2016. © 2015 Wiley Periodicals, Inc. PMID:26364758

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

    OpenAIRE

    Marko Kreft; Bak, Lasse K.; Waagepetersen, Helle S.; Arne Schousboe

    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.

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

    Directory of Open Access Journals (Sweden)

    Marko Kreft

    2012-04-01

    Full Text Available 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.

  14. 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 pat......-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....

  15. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

    OpenAIRE

    M. Ryan Smith; Vayalil, Praveen K.; Fen Zhou; Benavides, Gloria A; Beggs, Reena R.; Hafez Golzarian; Bhavitavya Nijampatnam; Oliver, Patsy G.; Smith, Robin A.J.; Murphy, Michael P.; Velu, Sadanandan E.; Aimee Landar

    2016-01-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compo...

  16. 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.

  17. Patterns of amino acid metabolism by proliferating human mesenchymal stem cells

    NARCIS (Netherlands)

    Higuera, G.A.; Schop, D.; Spitters, T.W.; Dijkhuizen, R.; Bracke, M.; Bruijn, J.D.; Martens, D.E.; Karperien, M.; Boxtel, van A.J.B.; Blitterswijk, van C.A.

    2012-01-01

    The nutritional requirements of stem cells have not been determined; in particular, the amino acid metabolism of stem cells is largely unknown. In this study, we investigated the amino acid metabolism of human mesenchymal stem cells (hMSCs), with focus on two questions: Which amino acids are consume

  18. Dynamics of human whole body amino acid metabolism

    International Nuclear Information System (INIS)

    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- [15N]- 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 15N-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.)

  19. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina;

    2014-01-01

    using a targeted proteomics analysis we have found that proteins involved in protein quality control and glycolytic enzymes are the main targets of oxidation (carbonylation) and modification with advanced glycation/lipid peroxidation end products during replicative senescence of satellite cells...... leading to increased mobilization of non-carbohydrate substrates as branched chain amino acids or long chain fatty acids was observed in senescent cells. In addition, phospho-and glycerolipids metabolism was altered. Increased levels of acyl-carnitines indicated augmented turnover of storage and membrane...... lipids for energy production. Such changes reflect alterations in membrane composition and dysregulation of sphingolipids signaling during senescence. This study establishes a new concept connecting oxidative protein modifications with the altered cellular metabolism associated with the senescent...

  20. Comparison of bare and amino modified mesoporous silica@poly(ethyleneimine)s xerogel as indomethacin carrier: Superiority of amino modification.

    Science.gov (United States)

    Li, Jing; Xu, Lu; Wang, Hongyu; Yang, Baixue; Liu, Hongzhuo; Pan, Weisan; Li, Sanming

    2016-02-01

    The purpose of this study was to facilely develop amino modified mesoporous silica xerogel synthesized using biomimetic method (B-AMSX) and to investigate its potential ability to be a drug carrier for loading poorly water-soluble drug indomethacin (IMC). For comparison, mesoporous silica xerogel without amino modification (B-MSX) was also synthesized using the same method. The changes of characteristics before and after IMC loading were systemically studied using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS) and nitrogen adsorption/desorption analysis. The results showed that B-MSX and B-AMSX were spherical nanoparticles with mesoporous structure. Compared with B-MSX, IMC loading capacity of B-AMSX was higher because more drug molecules can be loaded through stronger hydrogen bonding force. DSC and SAXS analysis confirmed the amorphous state of IMC after being loaded into B-MSX and B-AMSX. The in vitro drug release study revealed that B-MSX and B-AMSX improved IMC release significantly, and B-AMSX released IMC a little faster than B-MSX because of larger pore diameter of IMC-AMSX. B-MSX and B-AMSX degraded gradually in dissolution medium evidenced by color reaction and absorbance value, and B-AMSX degraded slower than B-MSX due to amino modification. In conclusion, B-AMSX with superiority of higher loading capacity and enhanced dissolution release can be considered to be a good candidate as drug carrier for IMC. PMID:26652425

  1. Proteins isolated from regenerating sciatic nerves of rats form aggregates following posttranslational amino acid modification

    International Nuclear Information System (INIS)

    Soluble proteins of regenerating sciatic nerves of rats can be posttranslationally, covalently modified by a variety of radioactive amino acids. The present study shows that once modified by a mixture of 15 amino acids, many of those proteins form aggregates that are unable to pass through a 0.45-micron filter and pellet following 20,000g centrifugation (suggesting a size of greater than 2 x 10(6) Da). Aggregation of proteins also occurs following modification by Arg or Lys alone, but does not occur following protein modification in nonregenerating nerves or in brain. Aggregates are not disrupted by treatment with 100 mM beta mercaptoethanol or by exposure to 1.0 M NaCl, but aggregates are solubilized by treatment with urea and by boiling in 1.5% SDS. Amino acid analysis of proteins modified by a mixture of [3H]amino acids shows a similar proportion of posttranslationally incorporated Ser, Pro, Val, Ala, Leu, Phe, Lys, and Arg in the soluble and pelletable fractions. Two-dimensional PAGE profiles of soluble and pelletable modified proteins show that the modified proteins in both fractions are in similar pI and molecular weight ranges, except that the soluble modified proteins include a high-molecular-weight component that is absent in the pelleted modified proteins. Kinetic studies show that while half-maximal levels of protein modification occur within 30 seconds of incubation, the appearance of the pelletable modified protein fraction is delayed significantly. These results indicate that amino acid modification of soluble proteins in regenerating sciatic nerves of rats results in physical changes in those proteins so that they form high-molecular-weight aggregates

  2. The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

    Science.gov (United States)

    Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

    2015-05-01

    Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

  3. Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition.

    Science.gov (United States)

    Mitchell, W Kyle; Wilkinson, Daniel J; Phillips, Bethan E; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J

    2016-07-01

    Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle "quality" decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies. PMID:27422520

  4. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels.

    Science.gov (United States)

    Smith, M Ryan; Vayalil, Praveen K; Zhou, Fen; Benavides, Gloria A; Beggs, Reena R; Golzarian, Hafez; Nijampatnam, Bhavitavya; Oliver, Patsy G; Smith, Robin A J; Murphy, Michael P; Velu, Sadanandan E; Landar, Aimee

    2016-08-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP), decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231) breast adenocarcinoma cells up to 6 days after an initial 24h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR) in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10µM) of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC) protein levels, although other protein levels were unaffected. This study

  5. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

    Directory of Open Access Journals (Sweden)

    M. Ryan Smith

    2016-08-01

    Full Text Available Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP, decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231 breast adenocarcinoma cells up to 6 days after an initial 24 h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10 µM of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC protein levels, although other protein levels were

  6. Tetrazine-Containing Amino Acid for Peptide Modification and Live Cell Labeling.

    Directory of Open Access Journals (Sweden)

    Zhongqiu Ni

    Full Text Available A novel amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl phenyl-2-aminopropanoic acid was synthesized in this study. The compound possessed better water-solubility and was synthesized more easily compared with the well-known and commercially available 3-(p-benzylamino-1, 2, 4, 5-tetrazine. Tetrazine-containing amino acid showed excellent stability in biological media and might be used for cancer cell labeling. Moreover, the compound remained relatively stable in 50% TFA/DCM with little decomposition after prolonged exposure at room temperature. The compound could be utilized as phenylalanine or tyrosine analogue in peptide modification, and the tetrazine-containing peptide demonstrated more significant biological activity than that of the parent peptide. The combination of tetrazine group and amino acid offered broad development prospects of the bioorthogonal labeling and peptide synthesis.

  7. 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 c

  8. 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.

  9. Effects of amino silicone oil modification on properties of ramie fiber and ramie fiber/polypropylene composites

    International Nuclear Information System (INIS)

    Highlights: • Ramie fiber (RF) changed to be hydrophobic after amino silicone oil modification. • Mechanical properties of RF/PP composites improved after fiber being modified. • N−H=O and O−H=N hydrogen bonds formed at the interface of modifier and fiber. • Amino silicone molecular interacts with cellulose in a preferred orientation. - Abstract: The effects of amino silicone oil modification on the properties of ramie fiber and ramie/polypropylene composites were investigated with experiments and molecular dynamics simulation. First, the effects of amino silicone oil treatments on the properties of ramie and ramie/polypropylene composites were investigated by experiments. The results indicated that the amino silicone oil modification can change the surface properties of ramie fiber from hydrophilic to hydrophobic and improve the mechanical properties of ramie/polypropylene composites. And then, the amino silicone oil modification mechanism at atomic and molecular levels was investigated by the molecular dynamics simulation. The simulation work elucidate that the surface modification mechanism can be described as: the amino silicone oil can interact with cellulose by the intermolecular forces, and the molecular chain of amino silicone oil tends to be an orientation that the hydrophobic alkyl groups project outward and the polar amino groups point to the surface of cellulose. Therefore, the surface of ramie fiber was covered with amino silicone oil, and the surface property of ramie fiber was changed from hydrophilic to hydrophobic. So the surface modification with amino silicone oil can improve the interfacial compatibility between ramie fiber and polymer

  10. 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.

  11. Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis and intermediary metabolism. Metabolic flux in developing maize kernels.

    Science.gov (United States)

    Glawischnig, E; Gierl, A; Tomas, A; Bacher, A; Eisenreich, W

    2001-03-01

    Information on metabolic networks could provide the basis for the design of targets for metabolic engineering. To study metabolic flux in cereals, developing maize (Zea mays) kernels were grown in sterile culture on medium containing [U-(13)C(6)]glucose or [1,2-(13)C(2)]acetate. After growth, amino acids, lipids, and sitosterol were isolated from kernels as well as from the cobs, and their (13)C isotopomer compositions were determined by quantitative nuclear magnetic resonance spectroscopy. The highly specific labeling patterns were used to analyze the metabolic pathways leading to amino acids and the triterpene on a quantitative basis. The data show that serine is generated from phosphoglycerate, as well as from glycine. Lysine is formed entirely via the diaminopimelate pathway and sitosterol is synthesized entirely via the mevalonate route. The labeling data of amino acids and sitosterol were used to reconstruct the labeling patterns of key metabolic intermediates (e.g. acetyl-coenzyme A, pyruvate, phosphoenolpyruvate, erythrose 4-phosphate, and Rib 5-phosphate) that revealed quantitative information about carbon flux in the intermediary metabolism of developing maize kernels. Exogenous acetate served as an efficient precursor of sitosterol, as well as of amino acids of the aspartate and glutamate family; in comparison, metabolites formed in the plastidic compartments showed low acetate incorporation. PMID:11244098

  12. Metabolic regulation of amino acid uptake in marine waters

    Energy Technology Data Exchange (ETDEWEB)

    Kirchman, D.L.; Hodson, R.E.

    1986-03-01

    To determine the relationships among the processes of uptake, intracellular pool formation, and incorporation of amino acids into protein, the authors measured the uptake of dipeptides and free amino acids by bacterial assemblages in estuarine and coastal waters of the southeast US. The dipeptide phenylalanyl-phenylalanine (phe-phe) lowered V/sub max/ of phenylalanine uptake when the turnover rate of phenylalanine was relatively high. When the turnover rate was relatively low, phe-phe either had no effect or increased V/sub max/ of phenylalanine uptake. An analytical model was developed and tested to measure the turnover time of the intracellular pool of phenylalanine. The results suggested that the size of the intracellular pool is regulated, which precludes high assimilation rates of both phenylalanine and phe-phe. In waters with relatively low phenylalanine turnover rates, bacterial assemblages appear to have a greater capacity to assimilate phenylalanine and phe-phe simultaneously. Marine bacterial assemblages do not substantially increase the apparent respiration of amino acids when concentrations increase. The authors conclude that sustained increases in uptake rates and mineralization by marine bacterial assemblages in response to an increase in the concentrations of dissolved organic nitrogen is determined by the rate of protein synthesis.

  13. Branched chain amino acids requirements and metabolism in pigs

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham

    2015-01-01

    investigation. A non-targeted metabolomics study was thereafter conducted in order to screen the bio-fluids of pigs for discriminating metabolites and identify biomarkers of BCAA, when the pigs were fed the optimum level of BCAA for the highest growth performance. The results of the Ile dose-response study...... requirements at 0.93. Metabolomics, one 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 approach in the current study provided novel knowledge of the metabolic response of pigs to increasing dietary BCAA and enabled us to identify the biomarkers of BCAA in plasma and urine of pigs when fed the optimum dietary Ile, Val, and Leu for the highest growth...

  14. Studies on amino acid metabolism in Lathyrus sativus Biosynthesis of homoserine and O-oxalylhomoserine

    Directory of Open Access Journals (Sweden)

    J. Przybylska

    2015-05-01

    Full Text Available Examination of free amino acid pool in Lathyrus sativus showed a rapid increase of homoserine and O-oxalylhomoserine during germination. Isotopic experiments indicated that aspartic acid was an effective precursor of homoserine in Lathyrus sativus and suggested oxalic acid to be incorporated into O-oxalylhomiaserine as an intact moiety. Similar trends of amino acid metabolism of Lathyrus sativus and of Pisum sativum have been discussed.

  15. Uptake and metabolism of dissolved amino acids by larvae and embryos of three gastropod species

    International Nuclear Information System (INIS)

    Dissolved organic matter is a potential nutritional resource for soft-bodied marine invertebrates. Experiments were done with developmental stages of three gastropod species to examine uptake kinetics and metabolism of dissolved amino acids. Free-swimming larvae of Crepidula fornicata and Thais-haemastoma were fed before experiments or starved for 48 hours before experiments to see whether nutritional state affected uptake of 14C-glycine of 14C-alanine. Time course of amino acid uptake was linear from 0-100 minutes for fed and starved larvae of both species. Uptake rates of starved T. haemastoma larvae were similar to or greater than rates for fed larvae, while uptake rates of starved C. fornicata larvae are similar to or less than rates for fed larvae. Starvation may enhance uptake by T. haemastoma larvae. 14CO2 was detected 10 minutes after larval exposure to labeled amino acids began, indicating rapid catabolism of amino acids. Label was found in protein extracted from larvae, indicating that absorbed glycine and alanine can be used for protein synthesis. A greater percent of glycine and alanine was converted to CO2 by starved larvae of both species. Encapsulated embryos of Nucella lapillus were used to study uptake and metabolism of amino acids because encapsulated embryos are in a bacteria-free environment. Uptake by embryos was linear from 10-90 minutes. Because capsules were bacteria-free embryos were the agents responsible for uptake and metabolism of labeled amino acids

  16. Comparative functional genomics of amino acid metabolism of lactic acid bacteria

    OpenAIRE

    Pastink, M.I.

    2009-01-01

    The amino acid metabolism of lactic acid bacteria used as starters in industrial fermentations has profound effects on the quality of the fermented foods. The work described in this PhD thesis was initiated to use genomics technologies and a comparative approach to link the gene content of some well-known lactic acid bacteria to flavor formation and to increase our general knowledge in the area of amino acid metabolism. The three well-known lactic acid bacteria that were used in these studies...

  17. Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria

    Institute of Scientific and Technical Information of China (English)

    Purnima; Guda; Chittibabu; Guda; Shankar; Subramaniam

    2007-01-01

    We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochon- dria. Human mitochondrial proteins determined by experimental and computa- tional methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mito- chondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which pre- dicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we recon- structed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.

  18. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    OpenAIRE

    Albert Mas; Jose Manuel Guillamon; Maria Jesus Torija; Gemma Beltran; Cerezo, Ana B; Troncoso, Ana M.; M. Carmen Garcia-Parrilla

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being und...

  19. 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

  20. Effect of plant proteins and crystalline amino acid supplementation on postprandial plasma amino acid profiles and metabolic response in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Rolland, Marine; Larsen, Bodil Katrine; Holm, Jørgen;

    2015-01-01

    The use of aquafeeds formulated with plant protein sources supplemented with crystalline amino acids (CAAs) is believed to influence amino acid (AA) uptake patterns and AA metabolic fate. Oxygen consumption and ammonia excretion rates were measured in rainbow trout (468.5 +/- A 86.5 g) force fed 0...

  1. 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...... activity (P < 0.05) and increased PDH kinase 4 mRNA (P < 0.05) during exercise and recovery. At 1 h of exercise, pyruvate production was greatest and was closely linked to glutamate, which was the predominant 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 in...

  2. TREATMENT OF THE METABOLIC SYNDROME: THE IMPACT OF LIFESTYLE MODIFICATION

    Science.gov (United States)

    Along with the increasing prevalence of obesity comes a constellation of metabolic derangements: dyslipidemias, hypertension, insulin resistance, and glucose intolerance, as well as increased prothrombotic and inflammatory markers. The association of these factors has been termed the "metabolic synd...

  3. Modern Techniques for Studying the Metabolism and Utilization of Nitrogenous Compounds, Especially Amino Acids

    International Nuclear Information System (INIS)

    Several techniques have been developed in recent years which make it possible to gain considerable insight into the manner in which compounds are utilized by animals, and to elucidate the role-of various substances in the synthetic processes that animals carry out. By utilizing these techniques it has become possible to determine the over-all metabolic fate of specific compounds in the animal; to establish how rapidly individual compounds are metabolized; and to identify various factors that influence the rate and extent of utilization of compounds by animals. Knowledge of this type is of great interest and is very important for better understanding metabolic processes and their regulation in animals. It seems likely that this type of information will provide the basis for influencing the metabolic fate of compounds in the animal and for ensuring more efficient utilization of substances for the desirable biosynthetic processes that animals carry out. Various techniques are discussed here that are being used to assess die metabolism and utilization of compounds in the intact animal and will give special attention to the role of the amino acids in lactating ruminants. Analysis of the respiratory patterns provides one method for evaluating the specific rate and extent of oxidation of 14C-labelled compounds after these are administered to animals. The rate of appearance of 14C in respired CO2, the time of maximum specific activity, and the subsequent decrease in specific activity, with time, reflect the role of individual compounds as sources of metabolic energy for the animal. The rate of disappearance of 14C-labelled compounds from the blood, with time, can be used to calculate turnover rates, pool sizes, and fluxes of metabolites through these pools. These parameters reflect the magnitude of the metabolic processes associated with utilization of specific compounds and they provide a basis for calculating the quantitative significance of the compound in the animal

  4. Functional analysis of gapped microbial genomes: amino acid metabolism of Thiobacillus ferrooxidans.

    Science.gov (United States)

    Selkov, E; Overbeek, R; Kogan, Y; Chu, L; Vonstein, V; Holmes, D; Silver, S; Haselkorn, R; Fonstein, M

    2000-03-28

    A gapped genome sequence of the biomining bacterium Thiobacillus ferrooxidans strain ATCC23270 was assembled from sheared DNA fragments (3.2-times coverage) into 1,912 contigs. A total of 2,712 potential genes (ORFs) were identified in 2.6 Mbp (megabase pairs) of Thiobacillus genomic sequence. Of these genes, 2,159 could be assigned functions by using the WIT-Pro/EMP genome analysis system, most with a high degree of certainty. Nine hundred of the genes have been assigned roles in metabolic pathways, producing an overview of cellular biosynthesis, bioenergetics, and catabolism. Sequence similarities, relative gene positions on the chromosome, and metabolic reconstruction (placement of gene products in metabolic pathways) were all used to aid gene assignments and for development of a functional overview. Amino acid biosynthesis was chosen to demonstrate the analytical capabilities of this approach. Only 10 expected enzymatic activities, of the nearly 150 involved in the biosynthesis of all 20 amino acids, are currently unassigned in the Thiobacillus genome. This result compares favorably with 10 missing genes for amino acid biosynthesis in the complete Escherichia coli genome. Gapped genome analysis can therefore give a decent picture of the central metabolism of a microorganism, equivalent to that of a complete sequence, at significantly lower cost. PMID:10737802

  5. Amino acid metabolism in tennis and its possible influence on the neuroendocrine system.

    OpenAIRE

    Strüder, H K; Hollmann, W; Duperly, J; Weber, K

    1995-01-01

    To investigate amino acid metabolism during endurance exercise as well as its influence on plasma prolactin (PRL) we subjected eight nationally ranked tennis players (mean(s.d.) age 25.6(2.8) years, mean(s.d.) weight 83.9(5.7) kg, mean(s.d.) height 184.4(4.6) cm) to 4h of continuous tournament tennis. Venous and capillary blood samples were taken before and after the exercise. Amino acids were measured by HPLC-fluorescence detection as o-phthalaldehyde derivatives; nonesterified fatty acids (...

  6. Metabolism of Aromatic Amino Acids during the Growth Cycle of Batch Suspension Cultures of Catharanthus roseus

    OpenAIRE

    Nagaoka, Noriko; ASHIHARA, Hiroshi

    1988-01-01

    Profiles of the levels and metabolism of aromatic compounds in suspension-cultured cells of Catharanthus roseus during the growth cycle were determined. The level of total protein-amino acids, i.e., sum of the amounts of amino acids in hydrolyzates of proteins, and the level of total phenolic acids increased after transfer of the cells in the stationary phase to fresh Murashige-Skoog medium. The maximum levels of the proteinamino acids and those of the phenolic acids were observed on days 3-5...

  7. Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-08-01

    Full Text Available Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

  8. Essential amino acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    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

  9. Lifestyle modification in the management of the metabolic syndrome: achievements and challenges

    Directory of Open Access Journals (Sweden)

    Riccardo Dalle Grave

    2010-11-01

    Full Text Available Riccardo Dalle Grave1, Simona Calugi1, Elena Centis2, Rebecca Marzocchi2, Marwan El Ghoch1, Giulio Marchesini21Department of Eating & Weight Disorder, Villa Garda Hospital, Garda (VR, Italy; 2Unit of Metabolic Diseases & Clinical Dietetics, Alma Mater Studiorum – University of Bologna, Bologna, ItalyAbstract: Lifestyle modification based on behavior therapy is the most important and effective strategy to manage the metabolic syndrome. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioral and cognitive strategies. The intervention may be delivered face-to-face or in groups, or in groups combined with individual sessions. The main challenge of treatment is helping patients maintain healthy behavior changes in the long term. In the last few years, several strategies have been evaluated to improve the long-term effect of lifestyle modification. Promising results have been achieved by combining lifestyle modification with pharmacotherapy, using meals replacement, setting higher physical activity goals, and long-term care. The key role of cognitive processes in the success/failure of weight loss and maintenance suggests that new cognitive procedures and strategies should be included in the traditional lifestyle modification interventions, in order to help patients build a mind-set favoring long-term lifestyle changes. These new strategies raise optimistic expectations for an effective treatment of metabolic syndrome with lifestyle modifications, provided public health programs to change the environment where patients live support them.Keywords: metabolic syndrome, obesity, lifestyle modification, cognitive behavior therapy

  10. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]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

  11. Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines

    International Nuclear Information System (INIS)

    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 [3H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([14C]aminocyclopentane carboxylic acid (ACPC) and [14C]aminoisobutyric acid (AIB)), and [18F]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 (K1) 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 (Vd) 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 K1 and Vd 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.)

  12. Characteristic metabolism of free amino acids in cetacean plasma: cluster analysis and comparison with mice.

    Directory of Open Access Journals (Sweden)

    Kazuki Miyaji

    Full Text Available From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaptation used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future.

  13. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue.

    Science.gov (United States)

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males' subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  14. 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.

  15. 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

  16. Trehalose 6-phosphate coordinates organic and amino acid metabolism with carbon availability.

    Science.gov (United States)

    Figueroa, Carlos M; Feil, Regina; Ishihara, Hirofumi; Watanabe, Mutsumi; Kölling, Katharina; Krause, Ursula; Höhne, Melanie; Encke, Beatrice; Plaxton, William C; Zeeman, Samuel C; Li, Zhi; Schulze, Waltraud X; Hoefgen, Rainer; Stitt, Mark; Lunn, John E

    2016-02-01

    Trehalose 6-phosphate (Tre6P) is an essential signal metabolite in plants, linking growth and development to carbon metabolism. The sucrose-Tre6P nexus model postulates that Tre6P acts as both a signal and negative feedback regulator of sucrose levels. To test this model, short-term metabolic responses to induced increases in Tre6P levels were investigated in Arabidopsis thaliana plants expressing the Escherichia coli Tre6P synthase gene (otsA) under the control of an ethanol-inducible promoter. Increased Tre6P levels led to a transient decrease in sucrose content, post-translational activation of nitrate reductase and phosphoenolpyruvate carboxylase, and increased levels of organic and amino acids. Radio-isotope ((14)CO2) and stable isotope ((13)CO2) labelling experiments showed no change in the rates of photoassimilate export in plants with elevated Tre6P, but increased labelling of organic acids. We conclude that high Tre6P levels decrease sucrose levels by stimulating nitrate assimilation and anaplerotic synthesis of organic acids, thereby diverting photoassimilates away from sucrose to generate carbon skeletons and fixed nitrogen for amino acid synthesis. These results are consistent with the sucrose-Tre6P nexus model, and implicate Tre6P in coordinating carbon and nitrogen metabolism in plants. PMID:26714615

  17. 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.

  18. [Modifications in myocardial energy metabolism in diabetic patients

    Science.gov (United States)

    Grynberg, A.

    2001-01-01

    The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by

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

    Science.gov (United States)

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

    1989-01-01

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

  20. Clinical aggressiveness of malignant gliomas is linked to augmented metabolism of amino acids.

    Science.gov (United States)

    Panosyan, Eduard H; Lasky, Joseph L; Lin, Henry J; Lai, Albert; Hai, Yang; Guo, Xiuqing; Quinn, Michael; Nelson, Stanley F; Cloughesy, Timothy F; Nghiemphu, P Leia

    2016-05-01

    Glutamine, glutamate, asparagine, and aspartate are involved in an enzyme-network that controls nitrogen metabolism. Branched-chain-amino-acid aminotransferase-1 (BCAT1) promotes proliferation of gliomas with wild-type IDH1 and is closely connected to the network. We hypothesized that metabolism of asparagine, glutamine, and branched-chain-amino-acids is associated with progression of malignant gliomas. Gene expression for asparagine synthetase (ASNS), glutaminase (GLS), and BCAT1 were analyzed in 164 gliomas from 156 patients [33-anaplastic gliomas (AG) and 131-glioblastomas (GBM), 64 of which were recurrent GBMs]. ASNS and GLS were twofold higher in GBMs versus AGs. BCAT1 was also higher in GBMs. ASNS expression was twofold higher in recurrent versus new GBMs. Five patients had serial samples: 4-showed higher ASNS and 3-higher GLS at recurrence. We analyzed grade and treatment in 4 groups: (1) low ASNS, GLS, and BCAT1 (n = 96); (2) low ASNS and GLS, but high BCAT1 (n = 26); (3) high ASNS or GLS, but low BCAT1 (n = 25); and (4) high ASNS or GLS and high BCAT1 (n = 17). Ninety-one  % of patients (29/32) with grade-III lesions were in group 1. In contrast, 95 % of patients (62/65) in groups 2-4 had GBMs. Treatment was similar in 4 groups (radiotherapy-80 %; temozolomide-30 %; other chemotherapy-50 %). High expression of ASNS, GLS, and BCAT1 were each associated with poor survival in the entire group. The combination of lower ASNS, GLS, and BCAT1 levels correlated with better survival for newly diagnosed GBMs (66 patients; P = 0.0039). Only tumors with lower enzymes showed improved outcome with temozolomide. IDH1(WT) gliomas had higher expression of these genes. Manipulation of amino acid metabolism in malignant gliomas may be further studied for therapeutics development. PMID:26922345

  1. Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

    Science.gov (United States)

    Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao

    2016-01-01

    This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697

  2. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Directory of Open Access Journals (Sweden)

    Albert Mas

    2014-01-01

    Full Text Available Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

  3. Water metabolism and modification of tritium excretion in the rat

    International Nuclear Information System (INIS)

    1. The intake and excretion of tritium were studied in rats exposed to tritiated water vapor. The metabolism of tritium was also investigated in rats given single administrations of tritiated water and in rats given daily administrations (per os or i.p.). The results were essentially in accord with those reported previously. 2. Amounts of drinking water consumed and urine excreted by rats drinking water with 0.15% saccharin were 1.5 to 2 times higher than in rats drinking tap water. The tritium activity in various tissues of rats drinking water with 0.15% saccharin decreased to about half of that of rats drinking tap water. A similar tendency was observed also in rats drinking beer. The diuretic agent sodium acetazolamide also enhanced the urinary excretion of tritium. (author)

  4. Essential amino-acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    As mentioned above, it was our intention to develop and test a simplified version of the protocol to assess amino acid metabolism in children. With the combined efforts of a team of experts in the field, a generic protocol was developed as a mandate of the first CRP held at Boston in the fall of 1993. During the beginning of 1994, the final version of such a protocol was released to all the participants of the CRP meeting and arrangements were made in order to apply it and assess its usefulness in the field setting. Therefore, we have shifted our activities to apply, assess and adapt the generic protocol. We are now testing the protocol in the field to establish the variability parameters in both between and within individuals. After testing and refining the protocol, with the help of other groups in developed countries, by validation and/or comparative studies, we would be in a better position to recommend it as a tool to study amino acid metabolism in children in developing countries, whether to describe some specific profiles or to evaluate nutrition interventions. 1 fig., 3 tabs

  5. 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

    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 c...... and glutamate extracted in increased amounts from the blood during exercise, are used for the synthesis of glutamine and for tricarboxylic-acid cycle anaplerosis.......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...

  6. 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

  7. Influence of Amino Acid Metabolism on Embryonic Stem Cell Function and Differentiation.

    Science.gov (United States)

    Kilberg, Michael S; Terada, Naohiro; Shan, Jixiu

    2016-07-01

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have promise in regenerative medicine because of their ability to differentiate into all 3 primary germ layers. This review describes recent advances in the understanding of the link between the metabolism of ESCs/iPSCs and their maintenance/differentiation in the cell culture setting, with particular emphasis on amino acid (AA) metabolism. ESCs are endowed with unique metabolic features with regard to energy consumption, metabolite flux through particular pathways, and macromolecular synthesis. Therefore, nutrient availability has a strong influence on stem cell growth, self-renewal, and lineage specification, both in vivo and in vitro. Evidence from several laboratories has documented that self-renewal and differentiation of mouse ESCs are critically dependent on proline metabolism, with downstream metabolites possibly serving as signal molecules. Likewise, catabolism of either threonine (mouse) or methionine (human) is required for growth and differentiation of ESCs because these AAs serve as precursors for donor molecules used in histone methylation and acetylation. Epigenetic mechanisms are recognized as critical steps in differentiation, and AA metabolism in ESCs appears to modulate these epigenetic processes. Recent reports also document that, in vitro, the nutrient composition of the culture medium in which ESCs are differentiated into embryoid bodies can influence lineage specification, leading to enrichment of a specific cell type. Although research designed to direct tissue specification of differentiating embryoid bodies in culture is still in its infancy, early results indicate that manipulation of the nutrient milieu can promote or suppress the formation of specific cell lineages. PMID:27422515

  8. 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.

  9. Targeted modification of storage protein content resulting in improved amino acid composition of barley grain

    DEFF Research Database (Denmark)

    Sikdar, Md. Shafiqul Islam; Bowra, S; Schmidt, Daiana;

    2016-01-01

    C-hordein in barley and ω-gliadins in wheat are members of the prolamins protein families. Prolamins are the major component of cereal storage proteins and composed of non-essential amino acids (AA) such as proline and glutamine therefore have low nutritional value. Using double stranded RNAi...... family members. Analysis of the AA composition of the transgenic lines showed that the level of essential amino acids increased with a concomitant reduction in proline and glutamine. Both the barley C-hordein and wheat ω-gliadin genes proved successful for RNAi-gene mediated suppression of barley C...

  10. Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

    International Nuclear Information System (INIS)

    Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VIIa, participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VIIa molecule, namely, 10 γ-carboxylated, N-terminally located glutamic acid residues, 1 β-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VIIa as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VIIa. By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradation, the protein backbone of recombinant factor VIIa was found to be identical with human factor VIIa. Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VIIa. In the recombinant factor VIIa, asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VIIa and human plasma factor VIIa. These results show that factor VIIa as produced in the transfected baby hamster kidney cells is very similar to human plasma factor VIIa and that this cell line thus might represent an alternative source for human factor VIIa

  11. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected].

    Directory of Open Access Journals (Sweden)

    Francois-Pierre J Martin

    Full Text Available Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2 under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

  12. Effects of Rumen-Protected Methionine on Dairy Performance and Amino Acid Metabolism in Lactating Cows

    Directory of Open Access Journals (Sweden)

    W. R. Yang

    2010-01-01

    Full Text Available Problem statement: Free Met as one of the most limiting AA in dairy cows would be mostly degraded in the rumen. This study was to determine the effect of different levels of Rumen-Protected Met (RPMet on dairy performance and serum amino acid metabolism. Approach: Thirty-six Holstein cows in similar condition were randomly assigned to six experimental treatments with six replicates each. Levels of RPMet in six treatments were 0(control, 14, 28, 42, 56 and 70 g day-1 per cow, respectively. Results: Treatment had no effect on percentage of milk protein, lactose and SNF. However, milk yield of cows fed 42 g day-1 RPMet was significantly higher than that of the control group and milk fat percentage was significantly increased with 56 g day-1 RPMet supplementation. There was the trend to decrease the concentration of serum amino acids except Met and Arg with the supplementation of RPMet. Serum EAA contents of the group supplementation of 42 g day-1 RPMet were lowest although there were no significant differences among all treatments. Serum BCAA concentrations of cows fed 28 g RPMet were significantly lower than that of the control group. Supplementation of 42 g RPMet could significantly decrease the concentration of NEAA and TAA compared to the control group. Conclusion/Recommendations: Supplementation of rumen-protected methionine improved dairy performance and promoted amino acid utilization in lactating cows in the present experiment. The optimal level of RPMet in the diet was 42 g per cow day-1.

  13. Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study

    International Nuclear Information System (INIS)

    Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-[11C]methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells

  14. Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, M.M.; Muhr, C.; Lundberg, P.O.; Bergstroem, K.G.; Gee, A.D.; Fasth, K.J.; Langstroem B5

    1987-09-01

    Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-(/sup 11/C)methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells.

  15. Genetic modifications in biosynthesis pathways of branched-chain-amino acids in Corynebacterium glutamicum

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav; Holátko, Jiří; Elišáková, Veronika

    Praha: Verlag, 2006, s. 142-142. [International Symposium on the Genetics of Industrial Microorganisms /10./. Praha (CZ), 24.06.2006-28.06.2006] R&D Projects: GA ČR GA525/04/0548 Institutional research plan: CEZ:AV0Z50200510 Keywords : corynebacterium glutamicum * genetic modifications Subject RIV: EE - Microbiology, Virology

  16. Program Management Model for Health Behavioral Modification in Metabolic Risk of Public Hospitals, Bangkok

    OpenAIRE

    Ungsinun Intarakamhang

    2012-01-01

    This action research is aimed to investigate the success of the program management for health behavioral modification (HBM) in Metabolic Syndrome (MS) of public hospitals in Bangkok which was granted by the 13th district of National Health Security Office (NHSO), Thailand, for the total of 13 projects. The research process was divided into 3 phases as preparation, monitoring and conclusion phase. Data collection was done in the mid and at the end of the project through a 4-scale questionnaire...

  17. A Branch Point of Streptomyces Sulfur Amino Acid Metabolism Controls the Production of Albomycin.

    Science.gov (United States)

    Kulkarni, Aditya; Zeng, Yu; Zhou, Wei; Van Lanen, Steven; Zhang, Weiwen; Chen, Shawn

    2016-01-01

    Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century. Although the productivity of S. griseus can be increased with random mutagenesis methods, understanding of Streptomyces sulfur amino acid (SAA) metabolism, which supplies a precursor for ABM biosynthesis, could lead to improved and stable production. We previously characterized the gene cluster (abm) in the genome-sequenced S. griseus strain and proposed that the sulfur atom of ABM is derived from either cysteine (Cys) or homocysteine (Hcy). The gene product, AbmD, appears to be an important link between primary and secondary sulfur metabolic pathways. Here, we show that propargylglycine or iron supplementation in growth media increased ABM production by significantly changing the relative concentrations of intracellular Cys and Hcy. An SAA metabolic network of S. griseus was constructed. Pathways toward increasing Hcy were shown to positively impact ABM production. The abmD gene and five genes that increased the Hcy/Cys ratio were assembled downstream of hrdBp promoter sequences and integrated into the chromosome for overexpression. The ABM titer of one engineered strain, SCAK3, in a chemically defined medium was consistently improved to levels ∼400% of the wild type. Finally, we analyzed the production and growth of SCAK3 in shake flasks for further process development. PMID:26519385

  18. EFFECTS OF CORDYCEPS SINENSIS PREPARATION ON BODY PROTEIN AND AMINO ACID METABOLISM IN PATIENTS AND RATS WITH CHRONIC RENAL FAILURE

    Institute of Scientific and Technical Information of China (English)

    朱淳; 刘强; 左静南; 朱汉威; 马济民

    2002-01-01

    Objective To study the effects of Cordyceps sinensis (CS) on the metabolism of body protein and intra-extracellular amino acids in patients with chronic renal failure( CRF) , and on the rates of protein synthesis in rats with CRF. Methods In patients with CRF, free amino acid concentrations in plasma and skeletal muscle before and after CS treatment were measured by the LKB-4400 amino acid automatic analytical instrument and the changes of body protein metabolism were observed by the method of 15 N-labeled glycine.Meanwhile, the rates of protein synthesis in liver ( SL % /d ) and muscle (SM%/d) of rats with CRF were determinedd by 3f-phenylalanine radioactive tracer. Results After patients with CRF were treated by CS, the Leu, lie, Thr , Lys, Cys, Tyr concentrations in plasma approached the normal levels. In one sample of skeletal muscle the Thr and Lys concentrations approached the normal, whereas both the intracellular and extracellular Val concentrations were still remarkably decreased as compared with the normal controls. Moreover, the nitrogen flow rate (Q) , rates of protein synthesis (S) and catabolism ( C) , and amino nitrogen utilization ratio (S/Q) in patients with CRF and the SL % /d and SM%/d in rats with CRF were significantly increased as compared with those before CS treatment. Conclusion CS can notably improve the amino acid metabolism, promote the body protein synthesis in patients with CRF , and increase the rates of SL % /d and SM%/d in rats with CRF.

  19. Stability of the larvicidal activity of Bacillus thuringiensis subsp. israelensis: amino acid modification and denaturants.

    OpenAIRE

    Pfannenstiel, M A; Couche, G A; G. Muthukumar; Nickerson, K W

    1985-01-01

    The Bacillus thuringiensis subsp. israelensis mosquito larvicidal toxin is not a sulfhydryl-activated toxin. The protein disulfide bonds were cleaved and blocked without loss of toxicity. In contrast, modification of the lysine side chains eliminated toxicity. Additionally, the toxin was resistant to high concentrations of salt (8 M NaBr), organic solvents (40% methanol), denaturants (4 M urea), and neutral detergents (10% Triton X-100). However, it was inactivated by both positively and nega...

  20. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation

    DEFF Research Database (Denmark)

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian;

    2015-01-01

    Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream proces...

  1. Sex Differences in Energy Metabolism Need to Be Considered with Lifestyle Modifications in Humans

    Directory of Open Access Journals (Sweden)

    Betty N. Wu

    2011-01-01

    Full Text Available Women have a higher proportion of body fat compared to men. However, women consume fewer kilojoules per kilogram lean mass and burn fat more preferentially during exercise compared with men. During gestation, women store even greater amounts of fat that cannot be solely attributed to increased energy intake. These observations suggest that the relationship between kilojoules consumed and kilojoules utilised is different in men and women. The reason for these sex differences in energy metabolism is not known; however, it may relate to sex steroids, differences in insulin resistance, or metabolic effects of other hormones such as leptin. When considering lifestyle modifications, sex differences in energy metabolism should be considered. Moreover, elucidating the regulatory role of hormones in energy homeostasis is important for understanding the pathogenesis of obesity and perhaps in the future may lead to ways to reduce body fat with less energy restriction.

  2. Prediction of posttranslational modification sites from amino acid sequences with kernel methods.

    Science.gov (United States)

    Xu, Yan; Wang, Xiaobo; Wang, Yongcui; Tian, Yingjie; Shao, Xiaojian; Wu, Ling-Yun; Deng, Naiyang

    2014-03-01

    Post-translational modification (PTM) is the chemical modification of a protein after its translation and one of the later steps in protein biosynthesis for many proteins. It plays an important role which modifies the end product of gene expression and contributes to biological processes and diseased conditions. However, the experimental methods for identifying PTM sites are both costly and time-consuming. Hence computational methods are highly desired. In this work, a novel encoding method PSPM (position-specific propensity matrices) is developed. Then a support vector machine (SVM) with the kernel matrix computed by PSPM is applied to predict the PTM sites. The experimental results indicate that the performance of new method is better or comparable with the existing methods. Therefore, the new method is a useful computational resource for the identification of PTM sites. A unified standalone software PTMPred is developed. It can be used to predict all types of PTM sites if the user provides the training datasets. The software can be freely downloaded from http://www.aporc.org/doc/wiki/PTMPred. PMID:24291233

  3. Tetra-amino-acid tandem repeats are involved in HsdS complementation in type IC restriction-modification systems.

    Science.gov (United States)

    Adamczyk-Popławska, Monika; Kondrzycka, Aneta; Urbanek, Katarzyna; Piekarowicz, Andrzej

    2003-11-01

    All known type I restriction and modification (R-M) systems of Escherichia coli and Salmonella enterica belong to one of four discrete families: type IA, IB, IC or ID. The classification of type I systems from a wide range of other genera is mainly based on complementation and molecular evidence derived from the comparison of the amino acid similarity of the corresponding subunits. This affiliation was seldom based on the strictest requirement for membership of a family, which depends on relatedness as demonstrated by complementation tests. This paper presents data indicating that the type I NgoAV R-M system from Neisseria gonorrhoeae, despite the very high identity of HsdM and HsdR subunits with members of the type IC family, does not show complementation with E. coli type IC R-M systems. Sequence analysis of the HsdS subunit of several different potential type IC R-M systems shows that the presence of different tetra-amino-acid sequence repeats, e.g. TAEL, LEAT, SEAL, TSEL, is characteristic for type IC R-M systems encoded by distantly related bacteria. The other regions of the HsdS subunits potentially responsible for subunit interaction are also different between a group of distantly related bacteria, but show high similarity within these bacteria. Complementation between the NgoAV R-M system and members of the EcoR124 R-M family can be restored by changing the tetra-amino-acid repeat within the HsdS subunit. The authors propose that the type IC family of R-M systems could consist of several complementation subgroups whose specificity would depend on differences in the conserved regions of the HsdS polypeptide. PMID:14600243

  4. Studies on Models,Patterns and Require-ments of Digestible Amino Acids for Layers by Nitrogen Metabolism

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The nitrogen (N) metabolic experiments were made to estimate separately amino acid requirements of 43~48 weeks old layers for maintenance, for protein accretion to estabolish models to estimate digestible amino acid requirements. The regression relationship of nitrogen retention vs amino acid intake was estimated for each amino acid by giving, at rate of N intake of 0.91, 0.52, 0.15 and 0.007g.kg-1 body-weight (W0.75) per d, the semi-synthetic diets was made specially deficient in one amino acid. From the regression coefficients, it was calculated that, for the accretion of 1 g protein, the dietary digestible amino acid requirements were (mg) Thr 63.1, Val 100.4, Met 39.9, Ile 88.6, Leu 114.3, Phe 63.2, Lys 87.0, His 20.5, Arg 87.9, Trp 21.4, Met+Cys 77.6, and Phe+Tyr 114.3. Daily amino acid requirements for N equilibrium were estimated to be (mg.kg-1W0.75 per day) Thr 50.6, Val 74.7, Met 30.3, ILe 66.7 Leu 81.4, Phe 44.8, Lys 60.5 His 14.7, Arg 73.9 ,Trp 17.3, Met+Cys 58.6, and Phe+Tyr 83.9 The dietary degestible amino acid patterns for protein accretion and N equilibrium were also proposed. The models of estimating digestible amino acid requirements for the different productions were developed.

  5. Molecule modification andmass deposition induced bythe implantation of lowenergy Fe+ ion beamsinto amino acids

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Fe+ ion beams with the energy of 110 keV were implanted into films of L(+)-cysteine (HSCH2CH(NH2)COOH). One of the single crystals grown in hydrochloric acid solution with the implanted samples through slow evaporation was structurally characterized by the X-ray crystallography. The crystal is monoclinic, space group C2, with a = 1.8534(4) nm, b = 0.5234(1) nm, c = 0.7212(1) nm, β= 103.72°, V = 0.67965(3) nm3, Z = 4, F(000) = 144.0, Dclac = 1.763 g@cm-3, μ(MoKα) = 1.06 mm-1, T = 293(2) K. R = 0.0379, wR = 0.0835 for 660 observed reflections (I > 2σ(I)). The structural formula of the crystal compound is (CH2CH(NH2)NO2)ClFe (Mr = 180.38 u). Products of heavy ion beam irradiation were purified and it was directly confirmed that the implanted Fe+ ions had been deposited in the novel molecules. The same doses of Fe+ ion beams of the same energy were implanted into films of L(+)-cysteine hydrochloride monohydrate. FTIR spectroscopy of the implanted samples proved that some of the original molecules were seriously damaged and significant modifications were induced.

  6. The cyanobacterial amino acid β-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats.

    Science.gov (United States)

    Engskog, Mikael K R; Karlsson, Oskar; Haglöf, Jakob; Elmsjö, Albert; Brittebo, Eva; Arvidsson, Torbjörn; Pettersson, Curt

    2013-10-01

    The neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) is produced by most cyanobacteria. BMAA is considered as a potential health threat because of its putative role in neurodegenerative diseases. We have previously observed cognitive disturbances and morphological brain changes in adult rodents exposed to BMAA during the development. The aim of this study was to characterize changes of major intermediary metabolites in serum following neonatal exposure to BMAA using a non-targeted metabolomic approach. NMR spectroscopy was used to obtain serum metabolic profiles from neonatal rats exposed to BMAA (40, 150, 460mg/kg) or vehicle on postnatal days 9-10. Multivariate data analysis of binned NMR data indicated metabolic pattern differences between the different treatment groups. In particular five metabolites, d-glucose, lactate, 3-hydroxybutyrate, creatine and acetate, were changed in serum of BMAA-treated neonatal rats. These metabolites are associated with changes in energy metabolism and amino acid metabolism. Further statistical analysis disclosed that all the identified serum metabolites in the lowest dose group were significantly (pBMAA. The demonstrated perturbation of intermediary metabolism may contribute to BMAA-induced developmental changes that result in long-term effects on adult brain function. PMID:23886855

  7. Engineering of nitrogen metabolism and its regulation in Corynebacterium glutamicum: influence on amino acid pools and production.

    Science.gov (United States)

    Rehm, Nadine; Burkovski, Andreas

    2011-01-01

    Nitrogen is one of the macronutrients necessary for living cells, and consequently, assimilation of nitrogen is a crucial step for metabolism. To satisfy their nitrogen demand and to ensure a sufficient nitrogen supply even in situations of nitrogen limitation, microorganisms have evolved sophisticated uptake and assimilation mechanisms for different nitrogen sources. This mini-review focuses on nitrogen metabolism and its control in the biotechnology workhorse Corynebacterium glutamicum, which is used for the industrial production of more than 2 million tons of L: -amino acids annually. Ammonium assimilation and connected control mechanisms on activity and transcription level are summarized, and the influence of mutations on amino acid pools and production is described with emphasis on L: -glutamate, L: -glutamine, and L: -lysine. PMID:20922371

  8. Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification.

    Science.gov (United States)

    Chen, Chen; Wang, Jiahong; Cai, Ruiping; Yuan, Yanmeng; Guo, Zhanyun; Grewer, Christof; Zhang, Zhou

    2016-01-01

    Sodium-coupled neutral amino acid transporter 2 (SNAT2) belongs to solute carrier 38 (SLC38) family of transporters, which is ubiquitously expressed in mammalian tissues and mediates transport of small, neutral amino acids, exemplified by alanine(Ala, A). Yet structural data on SNAT2, including the relevance of intrinsic cysteine residues on structure and function, is scarce, in spite of its essential roles in many tissues. To better define the potential of intrinsic cysteines to form disulfide bonds in SNAT2, mutagenesis experiments and thiol-specific chemical modifications by N-ethylmaleimide (NEM) and methoxy-polyethylene glycol maleimide (mPEG-Mal, MW 5000) were performed, with or without the reducing regent dithiothreitol (DTT) treatment. Seven single mutant transporters with various cysteine (Cys, C) to alanine (Ala, A) substitutions, and a C245,279A double mutant were introduced to SNAT2 with a hemagglutinin (HA) tag at the C-terminus. The results showed that the cells expressing C245A or C279A were labeled by one equivalent of mPEG-Mal in the presence of DTT, while wild-type or all the other single Cys to Ala mutants were modified by two equivalents of mPEG-Mal. Furthermore, the molecular weight of C245,279A was not changed in the presence or absence of DTT treatment. The results suggest a disulfide bond between Cys245 and Cys279 in SNAT2 which has no effect on cell surface trafficking, as well as transporter function. The proposed disulfide bond may be important to delineate proximity in the extracellular domain of SNAT2 and related proteins. PMID:27355203

  9. [3H]-amino acid uptake and metabolic studies on Gigantocotyle explanatum and Gastrothylax crumenifer (Digenea: Paramphistomidae)

    International Nuclear Information System (INIS)

    The amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer utilize leucine, alanine, proline and methionine during in vitro incubations. Autoradiography on sections of these flukes reveal a time-dependent differential incorporation of tritium-labelled amino acids in various tissues. The tegument appears to be the primary surface through which amino acids are absorbed. Following absorption, the reappearance of [3H]-leucine and [3H]-alanine on the tegumental surface during late chase periods indicates their possible involvement in tegumental secretion. A combination of diffusion and carrier-mediated uptake, possibly involving gamma-glutamyl transpeptidase, is indicated. The transport loci show differences in carrier-affinity (Kt) and maximum uptake velocities (Vmax) for amino acids under study, which suggest multiple transport molecules. Metabolic studies reveal that aspartate, alanine, ornithine, proline, leucine and methionine undergo transamination through 2-oxoglutarate-linked transaminases, distributed in the cytosolic and mitochondrial fractions of G. explanatum and G. crumenifer. With the exception of alanine transaminase, the enzyme levels in the cytosolic fraction were higher than the mitochondrial fraction of the two amphistomes. Predominantly cytosolic glutamate dehydrogenase which was comparatively higher in G. explanatum, catalyse amination of alpha-ketoglutarate. A high level of cytosolic arginase alone does not indicate a functional urea cycle. A tentative pathway of amino acid metabolism in these amphistomes is proposed

  10. Uptake of amino acids in brain tumours using positron emission tomography as an indicator for assessing metabolic activity and malignancy

    International Nuclear Information System (INIS)

    Diagnosis and post-therapeutic follow-up of tumour patients necessitates morphological and particularly functional imaging methods. For the latter approach positron emission tomography has proven a valid tool for the measurement of perfusion, of energy consumption parameters such as oxygen extraction, glucose metabolism and amino acid uptake. However, neither perfusion nor energy consumption parameters have yielded unambiguous information on the clinical status of various tumours in respect of their malignancy and their growth status. It is shown in this paper that amino acid uptake seems to be a valid measure for the functional activity of tumour tissue for a broad range of neoplasms. The uptake of 11C-L-Methionine was measured in 33 patients having various brain tumours, and was compared with 6 patients who had an infarction, and with 8 patients suffering from arachnoidal cysts. The amino acid uptake correlated well with the histological grading of the tumours and the clinical status of the patient. The uptake was well differentiated against metabolically inactive lesions. Parallel investigations on the uptake mechanisms of amino acids in an animal model have shown that transport phenomena regulate the uptake rather than protein synthesis rates. However, protein synthesis may nevertheless exercise a control function on the transport process. (orig.)

  11. Anesthesia with halothane and nitrous oxide alters protein and amino acid metabolism in dogs

    International Nuclear Information System (INIS)

    General anesthesia in combination with surgery is known to result in negative nitrogen balance. To determine whether general anesthesia without concomitant surgery decreases whole body protein synthesis and/or increases whole body protein breakdown, two groups of dogs were studied: Group 1 (n = 6) in the conscious state and Group 2 (n = 8) during general anesthesia employing halothane (1.5 MAC) in 50% nitrous oxide and oxygen. Changes in protein metabolism were estimated by isotope dilution techniques employing simultaneous infusions of [4,53H]leucine and alpha-[1-14C]-ketoisocaproate (KIC). Total leucine carbon flux was unchanged or slightly increased in the anesthetized animals when compared to the conscious controls, indicating only a slight increase in the rate of proteolysis. However, leucine oxidation was increased (P less than 0.001) by more than 80% in the anesthetized animals when compared with their conscious controls, whereas whole body nonoxidative leucine disappearance, an indicator of whole body protein synthesis, was decreased. The ratio of leucine oxidation to the nonoxidative rate of leucine disappearance, which provides an index of the catabolism of at least one essential amino acid in the postabsorptive state, was more than twofold increased (P less than 0.001) in the anesthetized animals regardless of the tracer employed. These studies suggest that the administration of anesthesia alone, without concomitant surgery, is associated with a decreased rate of whole body protein synthesis and increased leucine oxidation, resulting in increased leucine and protein catabolism, which may be underlying or initiating some of the protein wasting known to occur in patients undergoing surgery

  12. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary amino acid metabolism.

    Science.gov (United States)

    Larsen, M; Galindo, C; Ouellet, D R; Maxin, G; Kristensen, N B; Lapierre, H

    2015-11-01

    Nine Holstein cows with rumen cannulas and indwelling catheters in splanchnic blood vessels were used in a generalized randomized incomplete block design with repeated measures to study the effect of increased early postpartum AA supply on splanchnic and mammary AA metabolism. At calving, cows were blocked according to parity (second and third or greater) and allocated to 2 treatments: abomasal infusion of water (CTRL; n=4) or free AA with casein profile (AA-CN; n=5) in addition to a basal diet. The AA-CN infusion started with half of the maximal dose at the calving day (1 d in milk; DIM) and then steadily decreased from 791 to 226 g/d until 29 DIM. On 5, 15, and 29 DIM, 6 sample sets of arterial, portal, hepatic, and mammary blood were taken at 45-min intervals. Over the whole period, increasing AA supply increased milk (+7.8 ± 1.3 kg/d) and milk protein yields (+220 ± 65 g/d) substantially. The increased milk yield was not supported by greater dry matter intake (DMI) as, overall, DMI decreased with AA-CN (-1.6 ± 0.6 kg/d). Arterial concentrations of essential AA were greater for AA-CN compared with CTRL. The net portal-drained viscera (PDV) release of His, Met, and Phe was greater for AA-CN compared with CTRL, and the net PDV recovery of these infused AA ranged from 72 to 102% once changes in DMI were accounted for. The hepatic removal of these AA was increased equivalently to the increased net PDV release, resulting in an unaltered net splanchnic release. The net PDV release of Ile, Leu, Val, and Lys tended to be greater for AA-CN, and the net PDV recovery of these infused AA ranged from 69 to 73%, indicating increased PDV metabolism with AA-CN. The fractional hepatic removal of these AA did not differ from zero and was unaffected by the increased supply. Consequently, the splanchnic release of these AA was approximately equivalent to their net PDV release for both CTRL and AA-CN. Overall, greater early postpartum AA supply increased milk and milk protein

  13. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary amino acid metabolism

    DEFF Research Database (Denmark)

    Larsen, Mogens; Galindo, C; Ouellet, D R;

    2015-01-01

    blocked according to parity (second and third or greater) and allocated to 2 treatments: abomasal infusion of water (CTRL; n=4) or free AA with casein profile (AA-CN; n=5) in addition to a basal diet. The AA-CN infusion started with half of the maximal dose at the calving day (1 d in milk; DIM) and then......Nine Holstein cows with rumen cannulas and indwelling catheters in splanchnic blood vessels were used in a generalized randomized incomplete block design with repeated measures to study the effect of increased early postpartum AA supply on splanchnic and mammary AA metabolism. At calving, cows were...... steadily decreased from 791 to 226 g/d until 29 DIM. On 5, 15, and 29 DIM, 6 sample sets of arterial, portal, hepatic, and mammary blood were taken at 45-min intervals. Over the whole period, increasing AA supply increased milk (+7.8 ± 1.3 kg/d) and milk protein yields (+220 ± 65 g/d) substantially. The...

  14. Two food-borne heterocyclic amines: Metabolism and DNA adduct formation of amino-alpha-carbolines

    DEFF Research Database (Denmark)

    Frederiksen, Hanne

    2005-01-01

    -adducts have also been studied. Characteristic for the amino-a-carbolines are that relatively large amounts of these compounds in rat and human hepatic microsomes are activated to potent carcinogenic compounds compared with other heterocyclic amines, but further in vivo studies of the amino-a-carbolines are...

  15. Comparative analysis of RNA regulatory elements of amino acid metabolism genes in Actinobacteria

    Directory of Open Access Journals (Sweden)

    Gelfand Mikhail S

    2005-10-01

    Full Text Available Abstract Background Formation of alternative structures in mRNA in response to external stimuli, either direct or mediated by proteins or other RNAs, is a major mechanism of regulation of gene expression in bacteria. This mechanism has been studied in detail using experimental and computational approaches in proteobacteria and Firmicutes, but not in other groups of bacteria. Results Comparative analysis of amino acid biosynthesis operons in Actinobacteria resulted in identification of conserved regions upstream of several operons. Classical attenuators were predicted upstream of trp operons in Corynebacterium spp. and Streptomyces spp., and trpS and leuS genes in some Streptomyces spp. Candidate leader peptides with terminators were observed upstream of ilvB genes in Corynebacterium spp., Mycobacterium spp. and Streptomyces spp. Candidate leader peptides without obvious terminators were found upstream of cys operons in Mycobacterium spp. and several other species. A conserved pseudoknot (named LEU element was identified upstream of leuA operons in most Actinobacteria. Finally, T-boxes likely involved in the regulation of translation initiation were observed upstream of ileS genes from several Actinobacteria. Conclusion The metabolism of tryptophan, cysteine and leucine in Actinobacteria seems to be regulated on the RNA level. In some cases the mechanism is classical attenuation, but in many cases some components of attenuators are missing. The most interesting case seems to be the leuA operon preceded by the LEU element that may fold into a conserved pseudoknot or an alternative structure. A LEU element has been observed in a transposase gene from Bifidobacterium longum, but it is not conserved in genes encoding closely related transposases despite a very high level of protein similarity. One possibility is that the regulatory region of the leuA has been co-opted from some element involved in transposition. Analysis of phylogenetic patterns

  16. Global Proteome Analyses of Lysine Acetylation and Succinylation Reveal the Widespread Involvement of both Modification in Metabolism in the Embryo of Germinating Rice Seed.

    Science.gov (United States)

    He, Dongli; Wang, Qiong; Li, Ming; Damaris, Rebecca Njeri; Yi, Xingling; Cheng, Zhongyi; Yang, Pingfang

    2016-03-01

    Regulation of rice seed germination has been shown to mainly occur at post-transcriptional levels, of which the changes on proteome status is a major one. Lysine acetylation and succinylation are two prevalent protein post-translational modifications (PTMs) involved in multiple biological processes, especially for metabolism regulation. To investigate the potential mechanism controlling metabolism regulation in rice seed germination, we performed the lysine acetylation and succinylation analyses simultaneously. Using high-accuracy nano-LC-MS/MS in combination with the enrichment of lysine acetylated or succinylated peptides from digested embryonic proteins of 24 h after imbibition (HAI) rice seed, a total of 699 acetylated sites from 389 proteins and 665 succinylated sites from 261 proteins were identified. Among these modified lysine sites, 133 sites on 78 proteins were commonly modified by two PTMs. The overlapped PTM sites were more likely to be in polar acidic/basic amino acid regions and exposed on the protein surface. Both of the acetylated and succinylated proteins cover nearly all aspects of cellular functions. Ribosome complex and glycolysis/gluconeogenesis-related proteins were significantly enriched in both acetylated and succinylated protein profiles through KEGG enrichment and protein-protein interaction network analyses. The acetyl-CoA and succinyl-CoA metabolism-related enzymes were found to be extensively modified by both modifications, implying the functional interaction between the two PTMs. This study provides a rich resource to examine the modulation of the two PTMs on the metabolism pathway and other biological processes in germinating rice seed. PMID:26767346

  17. Metabolism and Modification of Apolipoprotein B-Containing Lipoproteins Involved in Dyslipidemia and Atherosclerosis.

    Science.gov (United States)

    Morita, Shin-ya

    2016-01-01

    Increased levels of apolipoprotein B (apoB)-containing lipoproteins, such as low density lipoproteins (LDL) and chylomicron remnants, are associated with the development of atherosclerosis. Chylomicrons containing apoB-48 are secreted from the intestine during the postprandial state, whereas very low density lipoproteins (VLDL) containing apoB-100 are constitutively formed in the liver. Chylomicron remnants and VLDL remnants are produced by the lipoprotein lipase-mediated lipolysis of triglycerides, which is activated by apolipoprotein C-II bound on the particle surfaces. The hepatic uptake of these remnants is facilitated by apolipoprotein E (apoE), but is inhibited by apolipoproteins C-I, C-II and C-III. In the plasma, VLDL remnants are further converted into LDL by the hydrolysis of triglycerides. ApoB-100 is responsible for the hepatic uptake of LDL. LDL receptor, LDL receptor-related protein and heparan sulfate proteoglycans are involved in the hepatic clearance of lipoproteins containing apoB-100 and/or apoE. The subendothelial retention and modification of apoB-containing lipoproteins are crucial events in the initiation of atherosclerosis. In the subendothelium, the uptake of modified lipoproteins by macrophages leads to the formation of foam cells storing excess amounts of cholesteryl esters and subsequently to apoptosis. This review describes the current knowledge about the metabolism and modification of apoB-containing lipoproteins involved in dyslipidemia and atherogenesis. In particular, I focus on the effects of apolipoproteins, lipid composition and particle size on lipoprotein metabolism and on the roles of cholesterol, sphingomyelinase and apoB denaturation in macrophage foam cell formation and apoptosis. A detailed understanding of these mechanisms will help to develop new therapeutic strategies. PMID:26725424

  18. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

    Energy Technology Data Exchange (ETDEWEB)

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.

  19. The cerebral metabolism of amino acids and related metabolites as studied by 13C and 14C labelling

    International Nuclear Information System (INIS)

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by 13C-and 14C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [13C[acetate, it was shown that glial cells export ∼60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [13C[glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of 13CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs

  20. Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids

    OpenAIRE

    You, Le; Page, Lawrence; Feng, Xueyang; Berla, Bert; Pakrasi, Himadri B; Yinjie J. Tang

    2012-01-01

    Microbes have complex metabolic pathways that can be investigated using biochemistry and functional genomics methods. One important technique to examine cell central metabolism and discover new enzymes is 13C-assisted metabolism analysis 1. This technique is based on isotopic labeling, whereby microbes are fed with a 13C labeled substrates. By tracing the atom transition paths between metabolites in the biochemical network, we can determine functional pathways and discover new ...

  1. Promoters inducible by aromatic amino acids and γ-aminobutyrate (GABA) for metabolic engineering applications in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kim, Sujin; Lee, Kyusung; Bae, Sang-Jeong; Hahn, Ji-Sook

    2015-03-01

    A wide range of promoters with different strengths and regulatory mechanisms are valuable tools in metabolic engineering and synthetic biology. While there are many constitutive promoters available, the number of inducible promoters is still limited for pathway engineering in Saccharomyces cerevisiae. Here, we constructed aromatic amino-acid-inducible promoters based on the binding sites of Aro80 transcription factor, which is involved in the catabolism of aromatic amino acids through transcriptional activation of ARO9 and ARO10 genes in response to aromatic amino acids. A dynamic range of tryptophan-inducible promoter strengths can be obtained by modulating the number of Aro80 binding sites, plasmid copy numbers, and tryptophan concentrations. Using low and high copy number plasmid vectors and different tryptophan concentrations, a 29-fold range of fluorescence intensities of enhanced green fluorescent protein (EGFP) reporter could be achieved from a synthetic U4C ARO9 promoter, which is composed of four repeats of Aro80 binding half site (CCG) and ARO9 core promoter element. The U4C ARO9 promoter was applied to express alsS and alsD genes from Bacillus subtilis for acetoin production in S. cerevisiae, resulting in a gradual increase in acetoin titers depending on tryptophan concentrations. Furthermore, we demonstrated that γ-aminobutyrate (GABA)-inducible UGA4 promoter, regulated by Uga3, can also be used in metabolic engineering as a dose-dependent inducible promoter. The wide range of controllable expression levels provided by these tryptophan- and GABA-inducible promoters might contribute to fine-tuning gene expression levels and timing for the optimization of pathways in metabolic engineering. PMID:25573467

  2. Adrenaline and reactive oxygen species elicit proteome and energetic metabolism modifications in freshly isolated rat cardiomyocytes

    International Nuclear Information System (INIS)

    cytosolic NADH/NAD+ ratio. Furthermore, an increase in manganese SOD expression and total SOD activity occurred in the ADR group, as the increase in the mitochondrial complexes presumably led to higher 'electron leakage'. The modifications in proteins, enzymes activity, and energetic metabolism were indicative that different pathways are activated by catecholamines and ROS. These alterations altogether determine the I/R and HF specific features and contribute for the initiation or aggravation of those cardiopathologic conditions.

  3. Post-synthetic modification of an amino-functionalized metal-organic framework for highly efficient enrichment of N-linked glycopeptides.

    Science.gov (United States)

    Ma, Wen; Xu, Linnan; Li, Ze; Sun, Yunlong; Bai, Yu; Liu, Huwei

    2016-06-01

    A maltose-functionalized metal-organic framework (MOF), MIL-101(Cr)-maltose, was developed via a simple two step post-synthetic modification of MIL-101(Cr)-NH2. With the use of this nanomaterial, 33 glycopeptides were detected from the digest of human immunoglobulin G, demonstrating its high efficiency in glycoproteomic analysis. More importantly, the generic functionalization route from amino-derived MOFs opens a new perspective in material design in sample preparation. PMID:27186633

  4. The metabolism of the non-proteinogenic amino acid β-N-methylamino-L-alanine (BMAA) in the cyanobacterium Synechocystis PCC6803.

    Science.gov (United States)

    Downing, Simoné; Downing, Timothy Grant

    2016-06-01

    The neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) is produced by cyanobacteria under nitrogen starvation conditions and its metabolism is closely associated with cellular nitrogen control. Very little is known regarding the metabolism or biosynthesis of this amino acid in the producing organisms and current knowledge is limited to the spontaneous formation of carbamate adducts in the presence of aqueous carbon dioxide, the rapid removal of free cellular BMAA upon the addition of ammonia to nitrogen-starved cyanobacterial cultures, and the link between cellular nitrogen status and BMAA synthesis. Data presented here show that exogenous BMAA is readily metabolised by cyanobacteria during which, the primary amino group is rapidly transferred to other cellular amino acids. Furthermore, data suggest that BMAA is metabolised in cyanobacteria via a reversible transamination reaction. This study presents novel data on BMAA metabolism in cyanobacteria and provides the first proposed biosynthetic precursor to BMAA biosynthesis in cyanobacteria. PMID:26948425

  5. Web application for genetic modification flux with database to estimate metabolic fluxes of genetic mutants.

    Science.gov (United States)

    Mohd Ali, Noorlin; Tsuboi, Ryo; Matsumoto, Yuta; Koishi, Daisuke; Inoue, Kentaro; Maeda, Kazuhiro; Kurata, Hiroyuki

    2016-07-01

    Computational analysis of metabolic fluxes is essential in understanding the structure and function of a metabolic network and in rationally designing genetically modified mutants for an engineering purpose. We had presented the genetic modification flux (GMF) that predicts the flux distribution of a broad range of genetically modified mutants. To enhance the feasibility and usability of GMF, we have developed a web application with a metabolic network database to predict a flux distribution of genetically modified mutants. One hundred and twelve data sets of Escherichia coli, Corynebacterium glutamicum, Saccharomyces cerevisiae, and Chinese hamster ovary were registered as standard models. PMID:26777238

  6. Sulfur amino acid metabolism in the whole body and mammary gland of the lactating Saanen goat

    International Nuclear Information System (INIS)

    Five multiparous Saanen goats in late lactation were infused with 35S-cysteine into the mammary gland via the external pudic artery. A further 2 goats were infused with 35S-methionine via the same artery and later with 35S-methionine into the jugular vein. Total uptake of cysteine from the arterial blood supply by the mammary gland was approximately 6% of the 35S-cysteine flux past the gland, whereas uptake of methionine was 30-40%. Total mammary uptake of cysteine was also lower than that of methionine when expressed as a percentage of whole body utilisation (6.5 and 14%, respectively). The uptake from the blood did not account for output in the milk for either cysteine or methionine. Both amino acids were highly conserved by the gland as shown by little release of any degraded constitutive protein amino acids and no evidence of oxidation products of either cysteine or methionine being released into the blood. Comparison of 35S activity in the milk from the infused and non-infused sides of the gland showed up to 10% trans-sulfuration of methionine to cysteine within the gland, none of which was exported in the venous drainage. Total ATP production by one side of the gland was 12.1 mol/day or 13 mmol/min.kg mammary tissue, of which 15% was required for gland protein synthesis. The experimental measurements from both the cysteine and methionine infusions were used to solve a model of gland amino acid uptake and partitioning. Modelling radioactivity of both amino acids in the blood, intracellular free pool, and milk protein suggested that a single intracellular pool cannot be the only source of amino acid for protein synthesis. The model also provides support for the hypothesis that a significant proportion of the uptake of at least some amino acids by the mammary gland is from intracellular hydrolysis of extracellularly derived peptides. Copyright (2001) CSIRO Australia

  7. Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

    Science.gov (United States)

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2015-11-01

    Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

    Roč. 47, č. 3 (2015), s. 603-615. ISSN 0939-4451 Institutional support: RVO:60077344 Keywords : Branched chain amino acid * nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * metabolomics and transcriptomics Subject RIV: CE - Biochemistry Impact factor: 3.293, year: 2014

  9. Comparison of amino acid oxidation and urea metabolism in haemodialysis patients during fasting and meal intake

    NARCIS (Netherlands)

    Veeneman, JM; Kingma, HA; Stellaard, F; de Jong, PE; Reijngoud, DJ; Huisman, RM

    2004-01-01

    Background. The PNA (protein equivalent of nitrogen appearance) is used to calculate protein intake from urea kinetics. One of the essential assumptions in the calculation of PNA is that urea accumulation in haemodialysis (HD) patients is equivalent to amino acid oxidation. However, urea is hydrolys

  10. Changes in metabolism and concentration of amino acids during yeast colony development

    Czech Academy of Sciences Publication Activity Database

    Váchová, Libuše; Begany, Markéta; Kučerová, Helena; Palková, Z.

    Dubrovnik : Verlag, 2006, s. 91-91. [EMBO/HHMI Central European Scientists Meeting. Dubrovnik (HR), 15.06.2006-17.06.2006] R&D Projects: GA ČR GA204/05/0294; GA MŠk(CZ) LC531 Institutional research plan: CEZ:AV0Z50200510 Keywords : amino acids * yeast colonies Subject RIV: EE - Microbiology, Virology

  11. Interactive effects of seawater acidification and elevated temperature on biomineralization and amino acid metabolism in the mussel Mytilus edulis.

    Science.gov (United States)

    Li, Shiguo; Liu, Chuang; Huang, Jingliang; Liu, Yangjia; Zheng, Guilan; Xie, Liping; Zhang, Rongqing

    2015-11-01

    Seawater acidification and warming resulting from anthropogenic production of carbon dioxide are increasing threats to marine ecosystems. Previous studies have documented the effects of either seawater acidification or warming on marine calcifiers; however, the combined effects of these stressors are poorly understood. In our study, we examined the interactive effects of elevated carbon dioxide partial pressure (P(CO2)) and temperature on biomineralization and amino acid content in an ecologically and economically important mussel, Mytilus edulis. Adult M. edulis were reared at different combinations of P(CO2) (pH 8.1 and 7.8) and temperature (19, 22 and 25°C) for 2 months. The results indicated that elevated P(CO2) significantly decreased the net calcification rate, the calcium content and the Ca/Mg ratio of the shells, induced the differential expression of biomineralization-related genes, modified shell ultrastructure and altered amino acid content, implying significant effects of seawater acidification on biomineralization and amino acid metabolism. Notably, elevated temperature enhanced the effects of seawater acidification on these parameters. The shell breaking force significantly decreased under elevated P(CO2), but the effect was not exacerbated by elevated temperature. The results suggest that the interactive effects of seawater acidification and elevated temperature on mussels are likely to have ecological and functional implications. This study is therefore helpful for better understanding the underlying effects of changing marine environments on mussels and other marine calcifiers. PMID:26417015

  12. PGC-1α-Mediated Branched-Chain Amino Acid Metabolism in the Skeletal Muscle

    OpenAIRE

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

    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, intracellula...

  13. Presymptomatic Alterations in Amino Acid Metabolism and DNA Methylation in the Cerebellum of a Murine Model of Niemann-Pick Type C Disease.

    Science.gov (United States)

    Kennedy, Barry E; Hundert, Amos S; Goguen, Donna; Weaver, Ian C G; Karten, Barbara

    2016-06-01

    The fatal neurodegenerative disorder Niemann-Pick type C (NPC) is caused in most cases by mutations in NPC1, which encodes the late endosomal NPC1 protein. Loss of NPC1 disrupts cholesterol trafficking from late endosomes to the endoplasmic reticulum and plasma membrane, causing cholesterol accumulation in late endosomes/lysosomes. Neurons are particularly vulnerable to this cholesterol trafficking defect, but the pathogenic mechanisms through which NPC1 deficiency causes neuronal dysfunction remain largely unknown. Herein, we have investigated amino acid metabolism in cerebella of NPC1-deficient mice at different stages of NPC disease. Imbalances in amino acid metabolism were evident from increased branched chain amino acid and asparagine levels and altered expression of key enzymes of glutamine/glutamate metabolism in presymptomatic and early symptomatic NPC1-deficient cerebellum. Increased levels of several amino acid intermediates of one-carbon metabolism indicated disturbances in folate and methylation pathways. Alterations in DNA methylation were apparent in decreased expression of DNA methyltransferase 3a and methyl-5'-cytosine-phosphodiester-guanine-domain binding proteins, reduced 5-methylcytosine immunoreactivity in the molecular and Purkinje cell layers, demethylation of genome-wide repetitive LINE-1 elements, and hypermethylation in specific promoter regions of single-copy genes in NPC1-deficient cerebellum at early stages of the disease. Alterations in amino acid metabolism and epigenetic changes in the cerebellum at presymptomatic stages of NPC disease represent previously unrecognized mechanisms of NPC pathogenesis. PMID:27083515

  14. Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

    Science.gov (United States)

    Tischler, M. E.; Jaspers, S. R.

    1985-01-01

    Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

  15. 3-Self behavior modification programs base on the PROMISE Model for clients at metabolic risk.

    Science.gov (United States)

    Intarakamhang, Ungsinun

    2012-01-01

    The objectives of this mixed methods research were 1) to study effects of the health behavior modification program (HBMP) conducted under the principles of the PROMISE Model and the CIPP Model and 2) to compare the 3-self health behaviors and the biomedical indicators before with after the program completion. During the program, three sample groups including 30 program leaders, 30 commanders and 120 clients were assessed, and there were assessments taken on 4,649 volunteers who were at risk of metabolic syndrome before and after the program conducted in 17 hospitals. The collected data were analyzed by the t-test and the path analysis. The research instruments were questionnaires used for program evaluation, structuralized interview forms, and questionnaires used for 3-self health behavior assessment. The findings were as follows: 1) During the program, the assessment result deriving from comparing the overall opinions toward the program among the three sample groups showed no difference (F=2.219), 2) The program management factors based on the PROMISE Model (positive reinforcement, optimism, context, and process or activity provision) had an overall influence on the product or success of the HBMP (pbehaviors (self-efficacy, self-regulation, and self-care) were significantly higher than those appeared before the participation (p< 0.05), and their biomedical indicators (BMI, blood pressure, waistline, blood glucose, lipid profiles, cholesterol, and HbA1c) were significantly lower than those measured before the program (p< 0.05). PMID:22980111

  16. Cloning of NruI and Sbo13I restriction and modification sstems in E. coli and amino acid sequence comparison of M.NruI and M.Sbo13I with other amino-methyltransferases

    Directory of Open Access Journals (Sweden)

    Benner Jack

    2010-05-01

    Full Text Available Abstract Background NruI and Sbo13I are restriction enzyme isoschizomers with the same recognition sequence 5' TCG↓CGA 3' (cleavage as indicated↓. Here we report the cloning of NruI and Sbo13I restriction-modification (R-M systems in E. coli. The NruI restriction endonuclease gene (nruIR was cloned by PCR and inverse PCR using primers designed from the N-terminal amino acid sequence. The NruI methylase gene (nruIM was derived by inverse PCR walking. Results The amino acid sequences of NruI endonuclease and methylase are very similar to the Sbo13I R-M system which has been cloned and expressed in E. coli by phage selection of a plasmid DNA library. Dot blot analysis using rabbit polyclonal antibodies to N6mA- or N4mC-modified DNA indicated that M.NruI is possibly a N6mA-type amino-methyltransferase that most likely modifies the external A in the 5' TCGCGA 3' sequence. M.Sbo13I, however, is implicated as a probable N4mC-type methylase since plasmid carrying sbo13IM gene is not restricted by Mrr endonuclease and Sbo13I digestion is not blocked by Dam methylation of the overlapping site. The amino acid sequence of M.NruI and M.Sbo13I did not show significant sequence similarity to many known amino-methyltransferases in the α, β, and γ groups, except to a few putative methylases in sequenced microbial genomes. Conclusions The order of the conserved amino acid motifs (blocks in M.NruI/M.Sbo13I is similar to the γ. group amino-methyltranferases, but with two distinct features: In motif IV, the sequence is DPPY instead of NPPY; there are two additional conserved motifs, IVa and Xa as extension of motifs IV and X, in this family of enzymes. We propose that M.NruI and M.Sbo13I form a subgroup in the γ group of amino-methyltransferases.

  17. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery

    DEFF Research Database (Denmark)

    Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin;

    2015-01-01

    180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption (VO2). RESULTS: Pathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG, FLOT1, EXOC7, RAB13......AIMS/HYPOTHESIS: The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite......, RABGAP1 and CBLB), glycolysis (HK2, PFKFB1, PFKFB3, PFKM, FBP2 and LDHA) and insulin signal mediators in diabetic participants compared with controls. Notably, diabetic participants had normalised rates of lactate and insulin levels, and of glucose appearance and disappearance, after exercise. They also...

  18. Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

    Directory of Open Access Journals (Sweden)

    Sebastiano Collino

    Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

  19. Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport.

    Directory of Open Access Journals (Sweden)

    Pricilla E Day

    Full Text Available Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content on a selection of metabolic and amino acid transporter genes and their associations with fetal growth.RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR.Increased placental LAT2 (p = 0.01, y+LAT2 (p = 0.03, aspartate aminotransferase 2 (p = 0.02 and decreased aspartate aminotransferase 1 (p = 0.04 mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01, ASCT1 (p = 0.03, mitochondrial branched chain aminotransferase (p = 0.02 and glutamine synthetase (p = 0.05 was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05 associated with higher maternal diet quality (prudent dietary pattern pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05 and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01 associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01. Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001.A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking

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

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord; Ott, Peter; Buhl, Mads; Vilstrup, Hendrik; Bak, Lasse Kristoffer; Waagepetersen, Helle Sønderby; Schousboe, Arne; Møller, Niels; Sørensen, Michael

    2011-01-01

    Branched-chain amino acids (BCAA) are used in attempts to reduce blood ammonia in patients with cirrhosis and intermittent hepatic encephalopathy based on the hypothesis that BCAA stimulate muscle ammonia detoxification. We studied the effects of an oral dose of BCAA on the skeletal muscle...... metabolism of ammonia and amino acids in 14 patients with cirrhosis and in 7 healthy subjects by combining [(13)N]ammonia positron emission tomography (PET) of the thigh muscle with measurements of blood flow and arteriovenous (A-V) concentrations of ammonia and amino acids. PET was used to measure the...

  1. The role of photosynthesis and amino acid metabolism in the energy status during seed development

    OpenAIRE

    Galili, Gad; Avin-Wittenberg, Tamar; Angelovici, Ruthie; Fernie, Alisdair R

    2014-01-01

    Seeds are the major organs responsible for the evolutionary upkeep of angiosperm plants. Seeds accumulate significant amounts of storage compounds used as nutrients and energy reserves during the initial stages of seed germination. The accumulation of storage compounds requires significant amounts of energy, the generation of which can be limited due to reduced penetration of oxygen and light particularly into the inner parts of seeds. In this review, we discuss the adjustment of seed metabol...

  2. Use of stable isotopes to assess protein and amino acid metabolism in children and adolescents: a brief review.

    Science.gov (United States)

    Darmaun, Dominique; Mauras, Nelly

    2005-01-01

    As protein accretion is a prerequisite for growth, studying the mechanisms by which nutrients and hormones promote protein gain is of the utmost relevance to paediatric endocrinology. Tracers are ideally suited for the assessment of protein and amino acid kinetics in vivo, as they provide an estimate of synthesis and turnover. Current tracer approaches in children and adolescents utilize stable isotopes, 'heavier' forms of elements that have one or several extra neutrons in the nucleus. Such isotopes are already present at low, but significant, levels in all tissues and foodstuffs, are not radioactive and are devoid of any known side-effects when present in small amounts. L-[1-(13)C] labelled leucine, given as a 4- to 6-h intravenous infusion, has become the method of choice to assess whole-body protein kinetics. After infusion, any 13C-leucine that is oxidized appears in the breath as 13CO2, whereas the remainder is incorporated into body proteins through protein synthesis. The isotope enrichments are determined by isotope ratio mass spectrometry and gas chromatography mass spectrometry, and absolute rates of whole-body protein synthesis, oxidation, and breakdown can be extrapolated. This approach has been used extensively to investigate the regulation of protein kinetics by nutrients and by hormones. Attempts have also been made to measure amino acid/protein metabolism in selected body compartments, and to measure the kinetics of specific tissue proteins, for example, muscle, gut, or plasma proteins. PMID:16439842

  3. Training and muscle ammonia and amino acid metabolism in humans during prolonged exercise

    DEFF Research Database (Denmark)

    Graham, T E; Turcotte, L P; Kiens, Bente;

    1995-01-01

    24.4 +/- 6.8 mmol/kg wet wt in Tr and Utr, respectively. Tr had greater (P < 0.05) muscle Tau, Phe, Ala, and Glu. Both groups had a large Glu uptake and effluxes of NH3, Gln, and Ala as well as essential AA. The latter implies that there was a net protein catabolism. The efflux of NH3 and Gln was...... much greater than that expected from AMP deamination, suggesting that deamination of AA was occurring. Many of the AA responses use Glu, and Tr maintained the intramuscular Glu pool at a higher concentration (P < 0.05), implying that they derived more Glu from protein catabolism and/or AA...... transaminations. Under these conditions, prolonged dynamic knee extensor exercise is associated with a large release of alpha-amino moieties both as NH3 and as Gln as well as a net protein catabolism; these responses are similar in Tr and Utr....

  4. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction.

    Science.gov (United States)

    Thackeray, James T; Bankstahl, Jens P; Wang, Yong; Wollert, Kai C; Bengel, Frank M

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (ptranslation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  5. Effect of Amino Acid Residue and Oligosaccharide Chain Chemical Modifications on Spectral and Hemagglutinating Activity of Millettia dielsiana Harms. ex Diels. Lectin

    Institute of Scientific and Technical Information of China (English)

    Shun GAO; Jie AN; Chuan-Fang WU; Ying GU; Fang CHEN; Yuan YU; Qia-Qing WU; Jin-Ku BAO

    2005-01-01

    The effects of modifying the carbohydrate chain and amino acids on the conformation and activity of Millettia dielsiana Harms. ex Diels. lectin (MDL) were studied by hemagglutination, fluorescence and circular dichroism analysis. The modification of tryptophan residues led to a compete loss of hemagglutinating activity; however, the addition of mannose was able to prevent this loss of activity. The results indicate that two tryptophan residues are involved in the carbohydrate-binding site. Modifications of the carboxyl group residues produced an 80% loss of activity, but the presence of mannose protected against the modification. The results suggest that the carboxyl groups of aspartic and glutamic acids are involved in the carbohydrate-binding site of the lectin. However, oxidation of the carbohydrate chain and modification of the histidine and arginine residues did not affect the hemagglutinating activity of MDL. Fluorescence studies of MDL indicate that tryptophan residues are present in a relatively hydrophobic region, and the binding of mannose to MDL could quench tryptophan fluorescence without any change in λmax. The circular dichroism spectrum showed that all of these modifications affected the conformation of the MDL molecule to different extents, except the modification of arginine residues. Fluorescence quenching showed that acrylamide and iodoacetic acids are able to quench 77% and 98% of the fluorescence of tryptophan in MDL, respectively.However, KI produced a barely perceptible effect on the fluorescence of MDL, even when the concentration of I- was 0.15 M. This demonstrates that most of tryptophan residues are located in relatively hydrophobic or negatively charged areas near the surface of the MDL molecule.

  6. Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

    OpenAIRE

    Petri Wiklund; Xiaobo Zhang; Satu Pekkala; Reija Autio; Lingjia Kong; Yifan Yang; Sirkka Keinänen-Kiukaanniemi; Markku Alen; Sulin Cheng

    2016-01-01

    Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectr...

  7. Functional analysis of gapped microbial genomes: Amino acid metabolism of Thiobacillus ferrooxidans

    OpenAIRE

    Selkov, Evgeni; Overbeek, Ross; Kogan, Yakov; Chu, Lien; Vonstein, Veronika; Holmes, David; Silver, Simon; Haselkorn, Robert; Fonstein, Michael

    2000-01-01

    A gapped genome sequence of the biomining bacterium Thiobacillus ferrooxidans strain ATCC23270 was assembled from sheared DNA fragments (3.2-times coverage) into 1,912 contigs. A total of 2,712 potential genes (ORFs) were identified in 2.6 Mbp (megabase pairs) of Thiobacillus genomic sequence. Of these genes, 2,159 could be assigned functions by using the WIT-Pro/EMP genome analysis system, most with a high degree of certainty. Nine hundred of the genes have been assigned roles in metabolic p...

  8. Effect of abomasal glucose infusion on splanchnic amino acid metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic AA metabolism. The experimental design was a split plot, with cow as the whole...... plot, treatment as the whole-plot factor and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: control or infusion of 1,500 g/d of glucose into the abomasum from the day of calving to 29 DIM....

  9. GlmS and NagB Regulate Amino Sugar Metabolism in Opposing Directions and Affect Streptococcus mutans Virulence

    Science.gov (United States)

    Kawada-Matsuo, Miki; Mazda, Yusuke; Oogai, Yuichi; Kajiya, Mikihito; Kawai, Toshihisa; Yamada, Sakuo; Miyawaki, Shouichi; Oho, Takahiko; Komatsuzawa, Hitoshi

    2012-01-01

    Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan) from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB) are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively. PMID:22438919

  10. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

    Directory of Open Access Journals (Sweden)

    Nengyi Zhang

    Full Text Available BACKGROUND: Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system. METHODOLOGY/PRINCIPAL FINDINGS: We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  11. Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.

    Science.gov (United States)

    Blohmke, Christoph J; Darton, Thomas C; Jones, Claire; Suarez, Nicolas M; Waddington, Claire S; Angus, Brian; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Kane, Leanne; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Duque-Correa, Maria A; Wright, James C; Roumeliotis, Theodoros I; Yu, Lu; Choudhary, Jyoti S; Mejias, Asuncion; Ramilo, Octavio; Shanyinde, Milensu; Sztein, Marcelo B; Kingsley, Robert A; Lockhart, Stephen; Levine, Myron M; Lynn, David J; Dougan, Gordon; Pollard, Andrew J

    2016-05-30

    Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. PMID:27217537

  12. The Impact of Streptozotocin-induced Diabetes Mellitus on Cyclic Nucleotide Regulation of Skeletal Muscle Amino Acid Metabolism in the Rat

    OpenAIRE

    Garber, Alan J.

    1980-01-01

    The impact of diabetes on cyclic nucleotide-associated mechanisms regulating skeletal muscle protein and amino acid metabolism was assessed using epitrochlaris preparations from streptozotocin-induced diabetic rats. 1 nM epinephrine inhibited alanine and glutamine release from control preparations, but no inhibition was observed from diabetic preparations with

  13. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    NARCIS (Netherlands)

    Costas, B.; Aragao, C.; Ruiz-Jarabo, I.; Vargas-Chacoff, L.; Arjona, F.J.; Mancera, J.M.; Dinis, M.T.; Conceicao, L.E.

    2012-01-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26 degrees C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino aci

  14. Fluorine-Tagged 5-Hydroxytryptophan to Investigate Amino Acid Metabolism In Vivo

    Directory of Open Access Journals (Sweden)

    Zofia E. Gagnon

    2010-01-01

    Full Text Available Auxin a plant growth hormone, has a metabolic pathway that includes molecules and enzymes like those in animal brains. In this study, tomato plant seedlings (Lycopersicon esculenta were used to investigate the fate of fluorine-tagged 5-hydroxytryptophan (PF-5-HTP being developed for fluorine spectroscopy and imaging. Seedlings were treated with high or low concentrations of 5-HTP or PF-5-HTP and compared with controls. Metabolites of the PF-5-HTP were quantified using a custom immunoassay for the tag. Serotonin (5-HT levels were measured with spectrofluorometry and thin-layer chromatography. Plants in treatment conditions had serotonin levels five to six times higher than controls. PF-5-HTP served as a precursor for serotonin in a biosynthetic pathway in this plant model, providing evidence for the bioavailability of the novel molecule. The increase in serotonin in plants grown in media culture supplemented with 5-HTP or PF-5-HTP might have useful applications in pharmacology.

  15. Fluorine-tagged 5-hydroxytryptophan to investigate amino Acid metabolism in vivo.

    Science.gov (United States)

    Gagnon, Zofia E; Dingman, Sherry; Thomas, Rhys N

    2010-01-01

    Auxin a plant growth hormone, has a metabolic pathway that includes molecules and enzymes like those in animal brains. In this study, tomato plant seedlings (Lycopersicon esculenta) were used to investigate the fate of fluorine-tagged 5-hydroxytryptophan (PF-5-HTP) being developed for fluorine spectroscopy and imaging. Seedlings were treated with high or low concentrations of 5-HTP or PF-5-HTP and compared with controls. Metabolites of the PF-5-HTP were quantified using a custom immunoassay for the tag. Serotonin (5-HT) levels were measured with spectrofluorometry and thin-layer chromatography. Plants in treatment conditions had serotonin levels five to six times higher than controls. PF-5-HTP served as a precursor for serotonin in a biosynthetic pathway in this plant model, providing evidence for the bioavailability of the novel molecule. The increase in serotonin in plants grown in media culture supplemented with 5-HTP or PF-5-HTP might have useful applications in pharmacology. PMID:22331995

  16. A new strategy for the selective determination of D-amino acids: enzymatic and chemical modifications for pre-column derivatization.

    Science.gov (United States)

    Oguri, Shigeyuki; Nomura, Michiko; Fujita, Youko

    2005-06-17

    A new strategy for the selective determination of D-amino acids (DAAs) employing a pre-column derivatization was designed with concepts based on both enzymatic and chemical modifications. Selective determination of DAAs was accomplished by following: DAA was enzymatically modified with D-amino acid oxidase (DAAO: EC 1.4.3.3) to form an alpha-keto acid. Subsequently, resulting alpha-keto acid was detected by high-performance liquid chromatography (HPLC) after chemical modification with o-phenylenediamine (PDA) in the presence of 2-mercaptoethanol (2ME) to give the corresponding quinoxalinol derivative (PDA-alpha-keto acid derivative). After optimizing the pre-column derivatization and HPLC separation, five peaks corresponding to DAAs (D-alanine, D-leucine, D-methionine, D-phenylalanine, D-valine (as the standard mixture of DAAs in this paper) were separately eluted and monitored by means of a conventional HPLC system with a gradient elution on octadecyl silica gel (ODS) column and a fluorescence detector (Ex.: 341 nm, Em.: 413 nm), respectively. It was confirmed that the present method was incapable of detecting L-amino acids (LAA) when a sample solution consisting of both LAAs and DAAs was examined. The linearity of the peak-area responses to their concentration range of DAAs from 10 to 500 microM is 0.994-1.000, and their detection limits were 0.2-1 microM (signal/noise = 3). When this method was applied to a methanolic extract of short-necked clams, Ruditapes philippinarum (in Japanese, Asari), a big peak, corresponding to D-alanine was detected, corresponding to 2.9 mg/g D-alanine. In this paper, we present an example of pre-column derivatization method that was newly configured to take into account both the biological and chemical properties of the substances in question. PMID:16007981

  17. Comparative Autoradiographic Study of the RNA and Protein Metabolism within the Various Tissues and Cells of the Mouse with Tritiated RNA Precursors and Labelled Amino Acids

    International Nuclear Information System (INIS)

    The first part of this report deals with autoradiographic studies of the incorporation of labelled amino acids into the various kinds of cells in mice and rats. The amount of the incorporation into the nucleus and into the cytoplasm was determined by grain counting. The results show that all nuclei within one cell-type and the nuclei of different cell-types have approximately the same incorporation rate per unit of nuclear volume. That means, that the amino acid incorporation within certain limits is generally proportional to the volume of a nucleus. Furthermore, the amino acid incorporation into the whole cytoplasm of the various examined cell-types was found to be 5 — 10 times greater than the nuclear incorporation. Therefore, the blackening distribution on autoradiographs with labelled amino acids can be understood by this simple incorporation scheme in connection with the varying size of the nuclear and cytoplasmatic volume of the different cell-types. On the other hand autoradiographic studies with tritiated cytidine and uridine have shown, that the incorporation of RNA precursors into the various tissues of mice and rats is proportional to that of amino acids. That suggests, that in all cells of the organism there exists a constant ratio between the size of protein metabolism and the size of (macromolecular) RNA metabolism. The protein metabolism in a cell is generally 20—30 times greater than the RNA metabolism. As in the case of amino acids incorporation the incorporation of tritiated cytidine into the nuclei of one cell-type and into the nuclei of different cell-types was found to be approximately proportional to the nuclear volume. (author)

  18. Free amino acid formula: nitrogen utilization and metabolic effects in normal subjects.

    Science.gov (United States)

    Heller, P A; Shronts, E; Akrabawi, S; Heymsfield, S B

    1987-01-01

    A previous study indicated increased urea production and low nitrogen (N) retention on a free amino acid elemental formula (FAA; Vivonex-HN). The limitations of this earlier study were: irregular nitrogen absorption in the malabsorption patients, high nitrogen intake, and failure to match FAA to control formula (hydrolyzed casein; CAS; Criticare-HN) with respect to kcal/nitrogen. A more critical test of FAA quality was sought in the current study. Four healthy males received the minimal daily nitrogen requirements (0.6 g protein/kg) from either FAA or CAS in a 10-day balance study; a second balance on the alternate formula followed. Maintenance energy, minerals, and vitamins were supplied in each period. The results indicated a higher apparent nitrogen absorption (p less than 0.05) from FAA relative to CAS in the first 5 days of the balance, although these differences were no longer present in the remaining 5 days of the period. Urinary total nitrogen increased on FAA, most of which could be accounted for by urea nitrogen; urinary creatinine nitrogen, ammonia nitrogen, and uric acid nitrogen were nearly identical between formulas. The unmeasured fraction of urinary nitrogen was markedly diminished on FAA while the urea nitrogen to total nitrogen ratio was significantly increased (p less than 0.05) compared to CAS. During the initial 5 days of study nitrogen balance was lower on FAA than on CAS and this difference became significant during the last 5 days of the period (mean +/- SD for FAA = -0.42 +/- 0.59 g/D vs CAS = 0.98 +/- 0.30 g/day, p less than 0.001). Hyperglycinemia was consistently present during FAA infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3430685

  19. 2,4-D and IAA Amino Acid Conjugates Show Distinct Metabolism in Arabidopsis

    Science.gov (United States)

    Eyer, Luděk; Vain, Thomas; Pařízková, Barbora; Oklestkova, Jana; Barbez, Elke; Kozubíková, Hana; Pospíšil, Tomáš; Wierzbicka, Roksana; Kleine-Vehn, Jürgen; Fránek, Milan; Strnad, Miroslav; Robert, Stéphanie

    2016-01-01

    The herbicide 2,4-D exhibits an auxinic activity and therefore can be used as a synthetic and traceable analog to study auxin-related responses. Here we identified that not only exogenous 2,4-D but also its amide-linked metabolite 2,4-D-Glu displayed an inhibitory effect on plant growth via the TIR1/AFB auxin-mediated signaling pathway. To further investigate 2,4-D metabolite conversion, identity and activity, we have developed a novel purification procedure based on the combination of ion exchange and immuno-specific sorbents combined with a sensitive liquid chromatography-mass spectrometry method. In 2,4-D treated samples, 2,4-D-Glu and 2,4-D-Asp were detected at 100-fold lower concentrations compared to 2,4-D levels, showing that 2,4-D can be metabolized in the plant. Moreover, 2,4-D-Asp and 2,4-D-Glu were identified as reversible forms of 2,4-D homeostasis that can be converted to free 2,4-D. This work paves the way to new studies of auxin action in plant development. PMID:27434212

  20. Proteomic investigation of protein profile changes and amino acid residue-level modification in cooked lamb longissimus thoracis et lumborum: The effect of roasting.

    Science.gov (United States)

    Yu, Tzer-Yang; Morton, James D; Clerens, Stefan; Dyer, Jolon M

    2016-09-01

    Protein modifications of meat cooked by typical dry-heat methods (e.g., roasting) are currently not well understood. The present study utilised a shotgun proteomic approach to examine the molecular-level effect of roasting on thin lamb longissimus thoracis et lumborum patties, in terms of changes to both the protein profile and amino acid residue side-chain modifications. Cooking caused aggregation of actin, myosin heavy chains and sarcoplasmic proteins. Longer roasting time resulted in significantly reduced protein extractability as well as protein truncation involving particularly a number of myofibrillar and sarcoplasmic proteins, e.g., 6-phosphofructokinase, beta-enolase, l-lactate dehydrogenase A chain, alpha-actinin-3, actin and possibly myosin heavy chains. Modifications that have potential influence on nutritional properties, including carboxyethyllysine and a potentially glucose-derived N-terminal Amadori compound, were observed in actin and myoglobin after roasting. This study provided new insights into molecular changes resulting from the dry-heat treatment of meat, such as commonly used in food preparation. PMID:27150797

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-12-01

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

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

    International Nuclear Information System (INIS)

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

  3. Evaluation of myocardial metabolism, with 13N- and 11C-labeled amino acids and positron computed tomography

    International Nuclear Information System (INIS)

    To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with 13N, and of 11C-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all 13N AA, and three (early, intermediate, late) for the two 11C compounds, with significantly different clearance half-times of 18.7 +/- 8.0 (s.d.) sec for the early phase, 141.7 +/- 56.5 sec for the intermediate, and 61.2 +/- 43.5 min for the late phase. The residual fractions ranged from 0.07 to 0.23 in normal myocardium, and consistently increased with ischemia by 0.01-0.07 for 13N-labeled Ala, Glu, Asp, and Leu, but not for 13N Gln and 11C compounds. Transaminase inhibition shortened the half-times of the late phases of 13N-labeled Ala, Glu, Asp, and Leu; had no effect on t1/2 of 13N Gln and 11C Oxal; and resulted in a loss of 11C CO2 production and of the intermediate phase for 11C Asp. On the PCT images, 13N activity from labeled Ala and Glu was not decreased in an ischemic segment despite a significant flow reduction, as demonstrated by 13N NH3 imaging and labeled microspheres. From the results, a three-compartment tracer kinetic model is proposed for the noninvasive quantification of Krebscycle activity, protein synthesis, and metabolic derangements related to ischemia

  4. The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons

    Directory of Open Access Journals (Sweden)

    Cezary Watala

    2013-11-01

    Full Text Available Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amidoamine (PAMAM dendrimers (G2, G3 and G4 have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.

  5. Potential use of carbon-11 labeled alpha-aminoisobutyric acid (AIB) as an in vivo tracer of amino acid uptake in differing metabolic states

    International Nuclear Information System (INIS)

    AIB has been used as a model amino acid for the evaluation of alanine-preferring amino acid transport. Hormonal factors and starvation alter the tissue distribution of amino acids, particularly in liver and muscle. With positron emission tomography and labeling of biochemical tracers with C-11, (t1/2=20.4 min), it is now possible to study amino acid kinetics in vivo using external imaging. In order to investigate the utility of C-11 AIB as an in vivo tracer of altered tissue metabolism, C-14 AIB was studied in groups of rats with either streptozotocin-induced diabetes, insulin-induced hypoglycemia or starvation. The data suggest an increased amino acid uptake in liver in starvation, an increased uptake in muscle in response to insulin and associated hypoglycemia and decreased transport in muscle in starvation, as seen by other investigators. These results suggest that C-11 AIB may be useful as an in vivo monitor of metabolic changes in body tissues

  6. Yuanhuapine-induced intestinal and hepatotoxicity were correlated with disturbance of amino acids, lipids, carbohydrate metabolism and gut microflora function: A rat urine metabonomic study.

    Science.gov (United States)

    Chen, Yanyan; Duan, Jin-Ao; Guo, Jianming; Shang, Erxin; Tang, Yuping; Qian, Yefei; Tao, Weiwei; Liu, Pei

    2016-07-15

    This research was designed to study metabonomic characteristics of the toxicity induced by yuanhuapine, a major bioactive diterpenoid in a well-known traditional Chinese medicine-Genkwa Flos. General observation, blood biochemistry and histopathological examination were used to reflect yuanhuapine-induced toxicity. Urine samples from rats in control and yuanhuapine treated rats were analyzed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Pattern recognition methods including principal components analysis (PCA), partial least-squared discriminant analysis (PLS-DA), orthogonal partial least-squared discriminant analysis (OPLS-DA) and computational system analysis were integrated to obtain comprehensive metabonomic profiling and pathways of the biological data sets. The results suggested that yuanhuapine could induce intestinal and liver damage. And 14 endogenous metabolites as biomarkers related to the amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora were significantly changed in the urine of yuanhuapine treated rats, which were firstly constructed the metabolomic feature profiling and metabolite interaction network of yuanhuapine-induced injury using pattern recognition methods and Ingenuity Pathway Analysis (IPA) approach. The present study showed that yuanhuapine-induced intestinal and hepatic toxicity were correlated with disturbance of amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora. PMID:26341729

  7. Ruminal protein metabolism and intestinal amino acid utilization as affected by dietary protein and carbohydrate sources in sheep.

    Science.gov (United States)

    Hussein, H S; Jordan, R M; Stern, M D

    1991-05-01

    Eight wether lambs fitted with ruminal, duodenal, and ileal cannulas were used in a replicated 4 x 4 Latin square design to study the effects of carbohydrate and protein sources on ruminal protein metabolism and carbohydrate fermentation and intestinal amino acid (AA) absorption. Treatments were arranged as a 2 x 2 factorial. Carbohydrate sources were corn and barley; protein sources were soybean meal (SBM) and fish meal (FM). Diets contained 15.5% CP, of which 40% was supplied by SBM or FM. Corn or barley provided 39% of dietary DM that contained equal amounts of grass hay and wheat straw. Fish meal diets produced a lower (P less than .05) ruminal NH3 concentration and resulted in less CP degradation and bacterial protein flow to the duodenum than did SBM diets. Replacing SBM with FM increased (P less than .05) ruminal digestion of all fiber fractions. In addition, cellulose and hemicellulose digestibilities in the rumen tended to increase (P greater than .05) when barley replaced corn in the FM diets. Carbohydrate x protein interactions (P less than .05) were observed for OM digestion in the rumen and AA absorption in the small intestine (percentage of AA entering); these interactions were highest for the barley-FM diet. These results suggest that feeding FM with barley, which is high in both degradable carbohydrate and protein, might benefit ruminants more than feeding FM with corn, which is high in degradable carbohydrate but relatively low in degradable protein. PMID:1648551

  8. THE DISTURBANCE OF METABOLISM OF THE AMINO ACIDS AS A CAUSATIVE FOR THE MENTAL RETARDATION-PHENYLKETONURIA

    Directory of Open Access Journals (Sweden)

    Jasmina IVANOVSKA

    2000-06-01

    Full Text Available PKU is the rare single-gene disease belonging to disturbance of metabolism of the amino acids, which in its own basics halved the mutated gene, whose leaning at the 12-chromosome charge for the synthesis of phenylalanine hydroxylase, turning on phenylalanine into tyrosine. Enzyme block usually leads to the accumulation of a toxic substrate and/or the deficient synthesis of a product needed for normal body function. In PKU there is a toxic accumulation of phenylalanine behind the deficient enzyme, phenylalanine hydrоxylase. The symptoms are: lighten hare, blue eyes, lithe pigmented skin, convulsion, mental retardation, low level of adrenalin caused for the lack of tyrosine, the urine have a specific smell of rats or gab.Inheritance of disease become in autosomal recessive way which always become possibility to stay hidden in the family and to inherit from knee to knee without manifestation of its own phenotype.The only therapy that successfully avoids the causes of this disease is phenylalanine-restricted diet. Today we have some affords for improvement of gene therapy, which can help us for determination to these disease. The success of the therapy depends from timing of the right detection also diagnostics all trough equivalent therapy which can successfully interrupt the new forms of mental retardation and other symptoms.

  9. [Effect of amino acid supplements to barley meal on the nitrogen metabolism of growing castrated male swine (20-65 kg live weight)].

    Science.gov (United States)

    Wecke, C; Gebhardt, G

    1981-03-01

    In 56 N-balance experiments of the influence of differentiated amino acid supplements to coarse barley meal enriched with energy, minerals and additives on the nitrogen metabolism of castrated male pigs, was investigated. The joint supplement of lysine and methionine remained without result in comparison with the sole supplementation of lysine. Only the additional supplementation of threonine resulted in the further improvement of protein utilisation. The results corroborate the effect of the amino acid lysine limiting the performance in barley protein and prove that threonine takes the second place in the sequence of limitation. PMID:6791610

  10. Modifications of the metabolic pathways of lipid and triacylglycerol production in microalgae

    Directory of Open Access Journals (Sweden)

    Yu Wei-Luen

    2011-11-01

    Full Text Available Abstract Microalgae have presented themselves as a strong candidate to replace diminishing oil reserves as a source of lipids for biofuels. Here we describe successful modifications of terrestrial plant lipid content which increase overall lipid production or shift the balance of lipid production towards lipid varieties more useful for biofuel production. Our discussion ranges from the biosynthetic pathways and rate limiting steps of triacylglycerol formation to enzymes required for the formation of triacylglycerol containing exotic lipids. Secondarily, we discuss techniques for genetic engineering and modification of various microalgae which can be combined with insights gained from research in higher plants to aid in the creation of production strains of microalgae.

  11. Effects of Various Dietary Amino Acid Preparations for Phenylketonuric Patients on the Metabolic Profiles along with Postprandial Insulin and Ghrelin Responses

    OpenAIRE

    Weigel, Corina; Rauh, Manfred; Kiener, C.; Rascher, Wolfgang; Knerr, Ina

    2013-01-01

    Aim: We investigated the metabolic profiles along with insulin and ghrelin responses following ingestion of various amino acid (AA) substitutes commonly used in the treatment of phenylketonuria to study the effects of added macronutrients. Methods: Twenty healthy and 6 phenylketonuric adults ingested AA mixtures with or without carbohydrates and fat (Anamix, Easiphen, or p-am 3; 0.35 g AA/kg body weight); milk powder shakes were used for control purposes. Serum AA, glucose, urea, insulin, and...

  12. N-Demethylation Is a Major Route of 2-Amino-3-Methylimidazo[4,5-f]quinoline Metabolism in Mouse

    OpenAIRE

    Lakshmi, Vijaya M.; Hsu, Fong Fu; Zenser, Terry V.

    2008-01-01

    2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) metabolism was evaluated in mouse to better understand its tumorigenicity. Urinary metabolites from mice orally administered 40 mg/kg [14C]IQ were compared with those from similarly treated rats. The recovery of radioactivity was significantly greater in mouse urine. The relative proportion of metabolites was significantly different, and a new rodent metabolite was detected. For rat, the proportion of previously identified metabolites excreted was ...

  13. Studies on the protein and amino acid metabolism of laying hens using 15N-labelled casein. 8

    International Nuclear Information System (INIS)

    Four colostomized Leghorn hens were fed, during 6 days, 15N-labelled casein as sole protein source. Two animals were slaughtered 48 hours, the other two 144 hours after the last 15N-application. The share of TCE-soluble N in total N averaged 16% for the body parts analysed, i.e. meat, bone, liver, kidneys, oviducts, residual viscera and other. The variation of the lysine, histidine and arginine levels in the body parts ranged from 3.6 to 7.9 g, 1.1 to 3.7 g and 6.4 to 7.4 g in 16.7 g hydrolysate N, respectively. Except for feathers, the analysed body parts contained an excess amount of heavy nitrogen. The degree of labelling was found to depend on the time of slaughtering after the tracer application. In the liver and in the oviduct being metabolically active organs, the 15N-excess in the total N fraction decreased by 45% between the 2nd and the 6th days after 15N-feeding, whilst in the meat it went down by 20%. The decline of the 15N-concentration in the TCE-soluble N compounds was faster than in the total N-fraction. Out of the body samples analysed, the lysine of the liver having 0.26 atom% 15N-excess was found to be more strongly labelled in hens 1 and 2. The amino acid arginine reached about the same level of labelling, the 15N-frequency of histidine being the lowest. (author)

  14. Effects of Denaturation and Amino Acid Modification on Fluorescence Spectrum and Hemagglutinating Activity of Hericium erinaceum Lectin

    Institute of Scientific and Technical Information of China (English)

    Meng GONG; Jie AN; Hong-Zhou LU; Chuan-Fang WU; Yi-Jin LI; Jing-Qiu CHENG; Jin-Ku BAO

    2004-01-01

    A sialic acid-binding lectin (Hericium erinaceum lectin, HEL), isolated from fresh fruiting bodies of Hericium erinaceum, was treated with various temperature and pH to investigate its fluorescencespectra and hemagglutinating activity. It was found that the hemagglutinating activity of HEL was relatively steady below 60℃ and at pH from 6 to 11, and the change of hemagglutinating activity was relative to thechange of hydrophobic areas where tryptophan residues located. In fluorescence quenching study of HEL byacrylamide and K1, it was indicated that nearly all the tryptophan residues of HEL located on the surface ofthe molecule, and most of them were in hydrophobic areas or negatively charged areas. Chemical modifica-tion of HEL proved that there were about twelve tryptophan residues in a HEL molecule and all of them werelocated on the surface or in the shallow groove of the molecule, and eight of them were essential for hemag-glutinating activity; aspartic acid or glutamic acid residues were involved in maintaining the crucial confor-mation of activity center and made great contribution to the hemagglutinating activity of HEL, but they could not touch the sialic acid molecule directly; tyrosine residues also played a role in the hemagglutinating activ-ity of HEL; while arginine, serine, threonine, histidine residues had no effect on the hemagglutinating activity of HEL.

  15. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... build up in the body. For these people, eating foods that are high in protein can cause serious health problems and, sometimes, death. People with these kinds of disorders may need to limit or avoid certain foods ...

  16. Experiment K-7-21: Effect of Microgravity on 1: Metabolic Enzymes of Type 1 and Type 2 Muscle Fibers, and on 2: Metabolic Enzymes, Neurotransmitter Amino Acids, and Neurotransmitter Associated Enzymes in Selected Regions of the Central Nervous System. Part 2; The Distribution of Selected Enzymes and Amino Acids in the Hippocampal Formation

    Science.gov (United States)

    Lowry, O. H.; Krasnov, I.; Ilyina-Kakueva, E. I.; Nemeth, P. M.; McDougal, D. B., Jr.; Choksi, R.; Carter, J. G.; Chi, M. M. Y.; Manchester, J. K.; Pusateri, M. E.

    1994-01-01

    Six key metabolic enzymes plus glutaminase and glutamate decarboxylase, as well as glutamate, aspartate and GABA, were measured in 11 regions of the hippocampal formation of synchronous, flight and tail suspension rats. Major differences were observed in the normal distribution patterns of each enzyme and amino acid, but no substantive effects of either microgravity or tail suspension on these patterns were clearly demonstrated.

  17. 3-Self Behavior Modification Programs Base on the PROMISE Model for Clients at Metabolic Risk

    OpenAIRE

    2012-01-01

    The objectives of this mixed methods research were 1) to study effects of the health behavior modification program (HBMP) conducted under the principles of the PROMISE Model and the CIPP Model and 2) to compare the 3-self health behaviors and the biomedical indicators before with after the program completion. During the program, three sample groups including 30 program leaders, 30 commanders and 120 clients were assessed, and there were assessments taken on 4,649 volunteers who were at risk o...

  18. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    International Nuclear Information System (INIS)

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  19. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    Science.gov (United States)

    Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

    2008-11-01

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  20. Effects of CO2 enrichment on the metabolism of soluble amino acids and organic acids in barley primary leaves

    Science.gov (United States)

    Responses of soluble amino acids and organic acids to CO2 enrichment were determined with barley primary leaves (Hordeum vulgare L. cv. Brant) grown in controlled environment chambers. Total soluble amino acids were enhanced 33% by CO2 enrichment when determined 9 days after sowing (DAS). However,...

  1. Potential protein post-translational modifications and find potential single amino acid substitutions in hepatitis B large envelope protein Posibles modificaciones postranslacionales y sustituciones de un solo aminoácido en la proteína grande de la superficie del virus de la hepatitis B

    OpenAIRE

    V Wiwanitkit

    2008-01-01

    Post-translational modifications of proteins control many biological processes. This is also important process in virus including hepatitis B. However, there is no in-depth study on the whole hepatitis B virus large envelope protein. In this work, potential protein post-translational modifications in hepatitis B virus large envelope protein were determined by a standard bioinformatics technique. Furthermore, potential single amino acid substitutions in hepatitis B large envelope protein were ...

  2. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    Science.gov (United States)

    Costas, Benjamín; Aragão, Cláudia; Ruiz-Jarabo, Ignacio; Vargas-Chacoff, Luis; Arjona, Francisco J; Mancera, Juan M; Dinis, Maria T; Conceição, Luís E C

    2012-07-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26°C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino acid changes during thermal acclimation. Senegalese sole maintained at 18°C were acclimated to either cold (12°C) or warm (26°C) environmental temperatures for 21 days. Fish maintained at 18°C served as control. Plasma concentrations of cortisol, glucose, lactate, triglycerides, proteins, and free amino acids were assessed. Cold acclimation influenced interrenal responses of sole by increasing cortisol release. Moreover, plasma glucose and lactate concentrations increased linearly with temperature, presumably reflecting a higher metabolic activity of sole acclimated to 26°C. Acclimation temperature affected more drastically plasma concentrations of dispensable than that of indispensable amino acids, and different acclimation temperatures induced different responses. Asparagine, glutamine and ornithine seem to be of particular importance for ammonia detoxification mechanisms, synthesis of triglycerides that may be used during homeoviscous adaptation and, to a lesser extent, as energetic substrates in specimens acclimated to 12°C. When sole is acclimated to 26°C taurine, glutamate, GABA and glycine increased, which may suggest important roles as antioxidant defences, in osmoregulatory processes and/or for energetic purposes at this thermal regimen. In conclusion, acclimation to different environmental temperatures induces several metabolic changes in Senegalese sole, suggesting that amino acids may be important for thermal acclimation. PMID:21947601

  3. Histidine and other amino acids in blood and urine after administration of Bretschneider solution (HTK) for cardioplegic arrest in patients: effects on N-metabolism.

    Science.gov (United States)

    Teloh, Johanna K; Dohle, Daniel-Sebastian; Petersen, Miriam; Verhaegh, Rabea; Waack, Indra N; Roehrborn, Friederike; Jakob, Heinz; de Groot, Herbert

    2016-06-01

    Bretschneider (histidine-tryptophan-ketoglutarate, HTK) solution employed for induction of cardioplegic arrest possesses a high histidine concentration (198 mM). Due to the large volume administered, massive amounts of histidine are incorporated. The aim of the study was to evaluate alterations in amino acid and nitrogen metabolism originating from histidine degradation. Between 07/2014 and 10/2014, a total of 29 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass (CPB) were enrolled in this prospective observational study. The patients received 1.6 L cardioplegic Bretschneider solution on average. Blood gas and urine samples obtained were analyzed for amino acid as well as urea and ammonium concentrations. After CPB initiation, plasma histidine concentration greatly increased to 21,000 µM to reach 8000 µM at the end. Within the operative period, plasma concentrations of aspartate, glutamate, asparagine, alanine, and glutamine increased variable in magnitude. During the same time, urinary analysis revealed histidine excretion of 19,500 µmol in total and marked elevations in glutamate and glutamine excretion. The absolute amounts of urea and ammonium excreted additionally were 3 mmol and 8 mmol, respectively. Already during CPB, distinct amounts of the histidine administered are metabolized, mainly to other amino acids, but only small amounts to urea and ammonia. Thus, the impact of the histidine incorporated on acid-base status in the intraoperative phase is minor. On the other hand, intraoperative provision of several amino acids arising from histidine metabolism might mitigate postaggression syndrome. PMID:26922473

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

    International Nuclear Information System (INIS)

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

  5. Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

    Science.gov (United States)

    Warren, Jeremy G; Lincoln, James E; Kirkpatrick, Bruce C

    2015-01-01

    Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or

  6. Proteomic Dissection of Endosperm Starch Granule Associated Proteins Reveals a Network Coordinating Starch Biosynthesis and Amino Acid Metabolism and Glycolysis in Rice Endosperms

    Science.gov (United States)

    Yu, Huatao; Wang, Tai

    2016-01-01

    Starch biosynthesis and starch granule packaging in cereal endosperms involve a coordinated action of starch biosynthesis enzymes and coordination with other metabolisms. Because directly binding to starch granules, starch granule-associated proteins (SGAPs) are essential to understand the underlying mechanisms, however the information on SGAPs remains largely unknown. Here, we dissected developmentally changed SGAPs from developing rice endosperms from 10 to 20 days after flowering (DAF). Starch granule packaging was not completed at 10 DAF, and was finished in the central endosperm at 15 DAF and in the whole endosperm at 20 DAF. Proteomic analysis with two-dimensional differential in-gel electrophoresis and mass spectrometry revealed 115 developmentally changed SGAPs, representing 37 unique proteins. 65% of the unique proteins had isoforms. 39% of the identified SGAPs were involved in starch biosynthesis with main functions in polyglucan elongation and granule structure trimming. Almost all proteins involved in starch biosynthesis, amino acid biosynthesis, glycolysis, protein folding, and PPDK pathways increased abundance as the endosperm developed, and were predicted in an interaction network. The network represents an important mechanism to orchestrate carbon partitioning among starch biosynthesis, amino acid biosynthesis and glycolysis for efficient starch and protein storage. These results provide novel insights into mechanisms of starch biosynthesis and its coordination with amino acid metabolisms and glycolysis in cereal endosperms. PMID:27252723

  7. 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...... during the first 29 DIM. Extra-splanchnic EAA mobilization can be crucial to sustain milk protein yield in the postpartum transition period and HMBi is a fast-working Met source that can improve Met status of postpartum transition cows....... difference: EAA excretion in milk protein − net portal absorption of EAA or net splanchnic release of EAA. Eight Holstein cows fitted with permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery in the dry period preceding second parturition were used in the...

  8. Effects of an eight-week supervised, structured lifestyle modification programme on anthropometric, metabolic and cardiovascular risk factors in severely obese adults.

    LENUS (Irish Health Repository)

    Crowe, Catherine

    2015-08-01

    Lifestyle modification is fundamental to obesity treatment, but few studies have described the effects of structured lifestyle programmes specifically in bariatric patients. We sought to describe changes in anthropometric and metabolic characteristics in a cohort of bariatric patients after participation in a nurse-led, structured lifestyle programme.

  9. Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes

    OpenAIRE

    Francisco Javier Ruiz-Ojeda; Carolina Gomez-Llorente; Concepción María Aguilera; Angel Gil; Azahara Iris Rupérez

    2016-01-01

    Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and inc...

  10. Modifications of xyloglucan metabolism in azuki bean epicotyls under hypergravity conditions

    Science.gov (United States)

    Soga, Kouichi; Arai, Kuninori; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Hoson, Takayuki

    We examined the effects of hypergravity on both the synthesis and the depolymerization processes of xyloglucan metabolisms. Azuki bean cuttings were incubated with [6-3H]-L-fucose, and the levels and the molecular size of synthesized xyloglucans were investigated in the upper growing regions of epicotyls. The amounts of radioactivity incorporated into xyloglucan fraction increased during incubation, irrespective of the gravity conditions. 3H-Xyloglucans were eluted in the higher molecular mass regions than xyloglucans already present in the cell wall. Hypergravity at 300 g did not influence the molecular size of newly deposited xyloglucans. Thus, the process of xyloglucan synthesis was not modified by the gravitational force. On the other hand, 3H-xyloglucans obtained from epicotyls grown at 1 g were shifted to the low molecular mass regions during the incubation period, which was inhibited by hypergravity. These results indicate that xyloglucans were deposited into the cell wall as large molecules but they were then depolymerized in the cell wall, and that the inhibition of the depolymerization is mainly responsible for the increase in the molecular size of xyloglucans under hypergravity conditions.

  11. Effect of Carbon and Nitrogen Availability on Metabolism of Amino Acids in Germinating Spores of Arbuscular Mycorrhizal Fungi

    Institute of Scientific and Technical Information of China (English)

    JIN Hai-Ru; JIANG Dong-Hua; ZHANG Ping-Hua

    2011-01-01

    The effects of carbon (C) and nitrogen (N) sources on N utilization and biosynthesis of amino acids were examined in the germinating spores of the arbuscular mycorrhizal (AM) fungus Glomus intraradices Schenck & Smith after exposure to various N substrates,CO2,glucose,and/or root exudates.The N uptake and de novo biosynthesis of amino acids were analyzed using stable isotopic labeling with mass spectrometric detection.High-performance liquid chromatography-based analysis was used to measure amino acid levels.In the absence of exogenous N sources and in the presence of 25 mL L-1 CO2,the germinating AM fungal spores utilized internal N storage as well as C skeletons derived from the degradation of storage lipids to biosynthesize the free amino acids,in which serine and glycine were produced predominantly.The concentrations of internal amino acids increased gradually as the germination time increased from 0 to 1 or 2 weeks.However,asparagine and glutamine declined to the low levels; both degraded to provide the biosynthesis of other amino acids with C and N donors.The availability of exogenous inorganic N (ammonium and nitrate) and organic N (urea,arginine,and glutamine) to the AM fungal spores using only CO2 for germination generated more than 5 times more internal free amino acids than those in the absence of exogenous N.A supply of exogenous nitrate to the AM fungal spores with only CO2 gave rise to more than 10 times more asparagine than that without exogenous N.In contrast,the extra supply of exogenous glucose to the AM fungal spores generated a significant enhancement in the uptake of exogenous N sources,with more than 3 times more free amino acids being produced than those supplied with only exogenous CO2.Meanwhile,arginine was the most abundant free amino acid produced and it was incorporated into the proteins of AM fungal spores to serve as an N storage compound.

  12. Amino Acid Metabolism of Thermoanaerobacter Strain AK90: The Role of Electron-Scavenging Systems in End Product Formation

    Directory of Open Access Journals (Sweden)

    Sean Michael Scully

    2015-01-01

    Full Text Available The catabolism of the 20 amino acids by Thermoanaerobacter strain AK90 (KR007667 was investigated under three different conditions: as single amino acids without an electron-scavenging system, in the presence of thiosulfate, and in coculture with a hydrogenotrophic methanogen. The strain degraded only serine without an alternative electron acceptor but degraded 11 amino acids (alanine, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tyrosine, and valine under both of the electron-scavenging systems investigated. Acetate was the dominant end product from alanine, cysteine, lysine, serine, and threonine under electron-scavenging conditions. The branched-chain amino acids, isoleucine, leucine, and valine, were degraded to their corresponding fatty acids under methanogenic conditions and to a mixture of their corresponding fatty acids and alcohols in the presence of thiosulfate. The partial pressure of hydrogen seems to be of importance for the branched-chain alcohol formation. This was suggested by low but detectable hydrogen concentrations at the end of cultivation on the branched-chain amino acid in the presence of thiosulfate but not when cocultured with the methanogen. A more detailed examination of the role of thiosulfate as an electron acceptor was performed with Thermoanaerobacter ethanolicus (DSM 2246 and Thermoanaerobacter brockii (DSM 1457.

  13. Has a mixture of amino acids and micronutrients influence on glucose metabolism and dietary fatty acid pattern in chronic psychosocially stressed persons? A pilot study.

    Science.gov (United States)

    Bitterlich, Norman; Chaborski, Katrin; Parsi, Elke; Rösler, Daniela; Metzner, Christine

    2016-01-01

    Brain food, e.g. L-tryptophan, antioxidative substances, B vitamins and magnesium are thought to be beneficial for obesity, inflammation and insulin resistance. In the present pilot study we hypothesised that a specific amino acid mixture with micronutrients improves the cardiometabolic situation of chronically stressed persons. Cardiovascular and metabolic parameters were analysed as per protocol in 32 patients. Chronic stress disorders in the same patients were assessed by a psychological neurological questionnaire (PNF). After dietary intervention a reduction of the fasting serum insulin concentrations occurred in the treatment group. An association was found between PNF values, insulin concentrations at baseline and an insulin reduction after 12 weeks. The results support the use of our specific dietary supplement for improved stress management and a decrease in metabolic dysfunction. PMID:26878772

  14. /sup 13/N-labeled L-amino acids for in vivo assessment of local myocardial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, F.J.; Barrio, J.R.; Henze, E.; Schelbert, H.R.; MacDonald, N.S.; Phelps, M.E.; Kuhl, D.E.

    1981-06-01

    The hot cell synthesis of sterile, pyrogen-free /sup 13/N-labeled L-amino acids was accomplished by employing the appropriate immobilized enzymes on a CNBr-activated Sepharose support and using remote, semiautomated systems. The syntheses were completed 6-12 min after cyclotron production of (/sup 13/N)ammonia. Myocardial time-activity curves after intracoronary injection of /sup 13/N-labeled L-amino acids in dogs were triexponential in both normal and ischemic myocardium. Higher retention of /sup 13/N activity was observed in ischemic segments. Positron computed tomography imaging also showed increased uptake of /sup 13/N-labeled L-glutamate and L-alanine in ischemic segments compared with normal myocardium when blood flow corrections were made. Myocardial transaminases are primarily responsible for the observed retention fractions. It suggests the participation of the carbon skeletons of these amino acids in the Krebs cycle.

  15. Mass spectrometric analysis of products of metabolic glycan engineering with azido-modification of sialic acids.

    Science.gov (United States)

    Bodnar, Edward; Raymond, Céline; Lopez, Paul G; Villacrés, Carina; Butler, Michael; Schoenhofen, Ian C; Durocher, Yves; Perreault, Hélène

    2015-12-01

    Metabolic engineering of glycans present on antibodies and other glycoproteins is becoming an interesting research area for improving our understanding of the glycome. With knowledge of the sialic acid biosynthetic pathways, the experiments described in this report are based on a published procedure involving the addition of a synthesized azido-mannosamine sugar into cell culture media and evaluation of downstream expression as azido-sialic acid. This unique bioorthogonal sugar has the potential for a variety of "click chemistry" reactions through the azide linkage, which allow for it to be isolated and quantified given the choice of label. In this report, mass spectrometry was used to investigate and optimize the cellular absorption of peracetylated N-azidoacetylmannosamine (Ac4ManNAz) to form N-azidoacetylneuraminic acid (SiaNAz) in a Chinese hamster ovary (CHO) cell line transiently expressing a double mutant trastuzumab (TZMm2), human galactosyltransferase 1 (GT), and human α-2,6-sialyltransferase (ST6). This in vivo approach is compared to in vitro enzymatic addition SiaNAz onto TZMm2 using soluble β-galactosamide α-2,6-sialyltransferase 1 and CMP-SiaNAz as donor. The in vivo results suggest that for this mAb, concentrations above 100 μM of Ac4ManNAz are necessary to allow for observation of terminal SiaNAz on tryptic peptides of TZMm2 by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. This is further confirmed by a parallel study on the production of EG2-hFc monoclonal antibody (Zhang J et al. Prot Expr Purific 65(1); 77-82, 2009) in the presence of increasing concentrations of Ac4ManNAz. PMID:26362153

  16. [Clinical picture of Hartnup disease. Without urine amino acids or any other identified metabolic disorder (a new entity)].

    Science.gov (United States)

    Da Gloria, E R; Assunção, J G; Costa, M A

    1990-01-01

    Harthnup disease clinical picture without aminoaciduria or other identified metabolic disturb (New entity?). The authors present a patient with clinical picture superposed to the Hartnup disease's, a rare, autosomic and recessive metabolic disturbance, characterized by typical aminoaciduria consequent to tryptophan and other neutral aminoacids defective transport by jejunal mucous membrane and renal tubules, clinically expressed by photosensitive pellagra-like dermatitis, mental retardation and intermittent cerebellar ataxia. The laboratorial results did not confirm Hartnup aminoaciduria nor other identified metabolic change that justify his clinical manifestations. PMID:2077308

  17. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 8

    International Nuclear Information System (INIS)

    Over 4 days 12 colostomized laying hens received, together with the ration, 36 g wheat with 14.37 atom-% 15N excess (15N'). The basic amino acids were nearly equally labelled. Three animals each were butchered after 12 h, 36 h, 60 h, and 108 h, resp., after the last 15N' application. Emission spectrometric determination of 15N' in liver and in amino acids was carried out. In addition, atom-% 15N' was determined in free amino acids and peptides. The labelling in the liver 12 h after the last 15N' application amounted to 1.75 atom-% 15N' and decreased after 108 h to 0.81 atom-% 15N'. The average TCA precipitable 15N' quota in the total 15N' amounted to 81.4% and was nearly identical at all four measuring points. The arginine 15N' amount in the liver was twice as high as that of lysine 15N'. In dependence on the period after the last 15N' application the decrease in the labelling of free arginine is considerable in comparison to free lysine. At the first measuring point (12 h) it was 1.69 atom-% 15N' and at the last one (108 h) 0.57 atom-% 15N'. Based on the results of 15N' labelling of peptides in the liver further, more detailed experiments for studies of peptide metabolism in the liver should be carried out. (author)

  18. In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos

    Directory of Open Access Journals (Sweden)

    Subrat K. Bhanja

    2015-04-01

    Full Text Available Due to their physicochemical and biological properties, silver nanoparticles (NanoAg have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10 expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2 expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4 expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken.

  19. In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos.

    Science.gov (United States)

    Bhanja, Subrat K; Hotowy, Anna; Mehra, Manish; Sawosz, Ewa; Pineda, Lane; Vadalasetty, Krishna Prasad; Kurantowicz, Natalia; Chwalibog, André

    2015-01-01

    Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10) expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2) expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4) expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken. PMID:25923079

  20. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.; Nielsen, Jens

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitation....

  1. Ion-pairing reversed-phase liquid chromatography/electrospray ionization mass spectrometric analysis of 76 underivatized amino acids of biological interest: a new tool for the diagnosis of inherited disorders of amino acid metabolism.

    Science.gov (United States)

    Piraud, Monique; Vianey-Saban, Christine; Petritis, Konstantinos; Elfakir, Claire; Steghens, Jean-Paul; Bouchu, Denis

    2005-01-01

    Seventy-six molecules of biological interest for the diagnosis of inherited disorders of amino acids (AA) metabolism have previously been demonstrated to be detectable in electrospray ionization tandem mass spectrometry (ESI-MS/MS) positive mode without derivatization. Reversed-phase liquid chromatography (RPLC) separation on different C18 columns using various perfluorinated carboxylic acids as ion-pairing agents has been found suitable for coupling with MS/MS, and for the separation of AA. A new procedure was optimized in order to replace the usual ion-exchange chromatographic, post-column ninhydrin derivatization, time-consuming routine method. This procedure allowed an adequate separation of all the molecules from other known interfering compounds, and a throughput of two samples per hour. Quantification limits for each molecule were found to be compatible with their measurement in plasma and urine. We validated the qualitative part of the method by analyzing plasma and urine samples from patients affected with several inherited disorders of AA metabolism. We validated the quantification of 16 AA using their stable isotopes as internal standard. The calibration curves were linear over the range 0-3 mM. The quantitative results obtained with the new method on 105 plasma and 99 urine samples were in good agreement with those obtained by the established routine method. Spiking experiments and precision results were also satisfactory. PMID:15915446

  2. Metabolism

    Science.gov (United States)

    ... also influenced by body composition — people with more muscle and less fat generally have higher BMRs. previous continue Things That Can Go Wrong With Metabolism Most of the time your metabolism works effectively ...

  3. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  4. Amino Acid Crossword Puzzle

    Science.gov (United States)

    Sims, Paul A.

    2011-01-01

    Learning the 20 standard amino acids is an essential component of an introductory course in biochemistry. Later in the course, the students study metabolism and learn about various catabolic and anabolic pathways involving amino acids. Learning new material or concepts often is easier if one can connect the new material to what one already knows;…

  5. Modulating the metabolic flux through the biosynthesis pathways of branched-chain amino acids in corynebacterium glutamicum

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav; Elišáková, Veronika; Holátko, Jiří

    2004, s. 53. [Metabolic Engineering /5./. Squaw Creek (US), 19.09.2004-23.09.2004] R&D Projects: GA ČR GA525/04/0548 Institutional research plan: CEZ:AV0Z5020903 Keywords : corynebacterium glutamicum * pathway Subject RIV: EE - Microbiology, Virology

  6. Application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report of an IAEA consultants' meeting held in Vienna, Austria, 14-16 December 1992

    International Nuclear Information System (INIS)

    A Consultants' Meeting convened by the IAEA in December 1992, made recommendations on the organization of a Co-ordinated Research Programme (CRP) using stable isotopic techniques for international comparative studies of amino acid, protein, and energy metabolism in chronically undernourished people. The CRP will use recent developments in stable isotope tracer techniques (13C and 15N) to assess the impact of infection in undernourished people on the kinetics of protein breakdown, protein synthesis, amino acid metabolism, and on the synthetic rates of selected plasma proteins. Studies will be conducted in developing countries, particularly in young children. The programme goals are to (i) elaborate methods and model protocols which can be implemented in developing countries to investigate the impact on protein metabolism of infection superimposed on chronic undernutrition; (ii) test they hypothesis that dietary requirements for protein and amino acids are related to the place of nutrition and are altered substantially when infection is superimposed on chronic undernutrition. When feasible, the primary focus on protein/amino acid metabolism will be extended to assessments of protein/energy interactions when H218O becomes more readily available and/or at research sites with indirect calorimetry equipment. The data generated should be appropriate as a basis for reevaluating amino acid/protein requirements in these populations. Refs

  7. Amino acids

    Science.gov (United States)

    Amino acids are organic compounds that combine to form proteins . Amino acids and proteins are the building blocks of life. When proteins are digested or broken down, amino acids are left. The human body uses amino acids ...

  8. Skin metabolism of aminophenols: Human keratinocytes as a suitable in vitro model to qualitatively predict the dermal transformation of 4-amino-2-hydroxytoluene in vivo

    International Nuclear Information System (INIS)

    4-Amino-2-hydroxytolune (AHT) is an aromatic amine ingredient in oxidative hair colouring products. As skin contact occurs during hair dyeing, characterisation of dermal metabolism is important for the safety assessment of this chemical class. We have compared the metabolism of AHT in the human keratinocyte cell line HaCaT with that observed ex-vivo in human skin and in vivo (topical application versus oral (p.o.) and intravenous (i.v.) route). Three major metabolites of AHT were excreted, i.e. N-acetyl-AHT, AHT-sulfate and AHT-glucuronide. When 12.5 mg/kg AHT was applied topically, the relative amounts of each metabolite were altered such that N-acetyl-AHT product was the major metabolite (66% of the dose in comparison with 37% and 32% of the same applied dose after i.v. and p.o. administration, respectively). N-acetylated products were the only metabolites detected in HaCaT cells and ex-vivo whole human skin discs for AHT and p-aminophenol (PAP), an aromatic amine known to undergo N-acetylation in vivo. Since N-acetyltransferase 1 (NAT1) is the responsible enzyme, kinetics of AHT was further compared to the standard NAT1 substrate p-aminobenzoic acid (PABA) in the HaCaT model revealing similar values for Km and Vmax. In conclusion NAT1 dependent dermal N-acetylation of AHT represents a 'first-pass' metabolism effect in the skin prior to entering the systemic circulation. Since the HaCaT cell model represents a suitable in vitro assay for addressing the qualitative contribution of the skin to the metabolism of topically-applied aromatic amines it may contribute to a reduction in animal testing

  9. The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

    OpenAIRE

    Rees, William; Hay, Susan; Antipatis, Christos

    2006-01-01

    International audience To characterise the effects of dietary protein content on threonine metabolism during pregnancy, rats were fed diets containing 18% or 9% protein and then killed at different stages of gestation. Serum threonine concentrations fell significantly faster in the animals fed the diet containing 9% protein when compared to those fed the diet containing 18% protein. On day 4 of gestation the rate of threonine oxidation was higher in maternal liver homogenates prepared from...

  10. Methodical investigation of the protein metabolism and of the bioenergetics of the protein retention in growing animals. 2. Results of the analysis of the amino acids after the long-term labelling of chickens with /sup 15/N-acetate

    Energy Technology Data Exchange (ETDEWEB)

    Voelker, T.; Krawielitzki, K.; Klein, M. (Akademie der Landwirtschaftswissenschaften der DDR, Dummerstorf-Rostock. Forschungszentrum fuer Tierproduktion); Keller, J. (Polska Akademia Nauk, Jastrzebiec. Inst. Genetyki i Hodowli Zwierzat)

    The amino acid composition of the proteins in selected body fractions of chickens and the /sup 15/N -excess of amino acids isolated from them resulting from a feeding experiment with long-term /sup 15/NH/sub 4/-acetate labelling were determined. The amino acid spectra of feathers, breast and leg muscles are characterized by differences in the content of individual amino acids specific for the organs, the composition of the proteins, however, is independent of the protein content of the ration and the age of the animals. The sarcoplasmatic and myofibrillar proteins also have typical amino acid patterns, which-with the exception of the histidine content-are neither influenced by the extraction of the proteins from the breast or leg muscles nor by the energy level of the feeding or the age of the animals. There are no significant differences in the metabolization of the main protein fraction of the breast and leg muscles. The oral supply of /sup 15/N-ammonium acetate to broilers predominantly labels the non-essential amino acids so that the derived kinetic data chiefly represent the metabolism of the non-essential amino acids.

  11. Metabolic Diseases Downregulate the Majority of Histone Modification Enzymes, Making a Few Upregulated Enzymes Novel Therapeutic Targets-"Sand Out and Gold Stays".

    Science.gov (United States)

    Shao, Ying; Chernaya, Valeria; Johnson, Candice; Yang, William Y; Cueto, Ramon; Sha, Xiaojin; Zhang, Yi; Qin, Xuebin; Sun, Jianxin; Choi, Eric T; Wang, Hong; Yang, Xiao-Feng

    2016-02-01

    To determine whether the expression of histone modification enzymes is regulated in physiological and pathological conditions, we took an experimental database mining approach pioneered in our labs to determine a panoramic expression profile of 164 enzymes in 19 human and 17 murine tissues. We have made the following significant findings: (1) Histone enzymes are differentially expressed in cardiovascular, immune, and other tissues; (2) our new pyramid model showed that heart and T cells are among a few tissues in which histone acetylation/deacetylation, and histone methylation/demethylation are in the highest varieties; and (3) histone enzymes are more downregulated than upregulated in metabolic diseases and regulatory T cell (Treg) polarization/ differentiation, but not in tumors. These results have demonstrated a new working model of "Sand out and Gold stays," where more downregulation than upregulation of histone enzymes in metabolic diseases makes a few upregulated enzymes the potential novel therapeutic targets in metabolic diseases and Treg activity. PMID:26746407

  12. A new reversed-phase liquid chromatographic/tandem mass spectrometric method for analysis of underivatised amino acids: evaluation for the diagnosis and the management of inherited disorders of amino acid metabolism.

    Science.gov (United States)

    Piraud, M; Vianey-Saban, C; Bourdin, C; Acquaviva-Bourdain, C; Boyer, S; Elfakir, C; Bouchu, D

    2005-01-01

    Seventy-six compounds of biological interest for the diagnosis of inherited disorders of amino acids (AA) metabolism have previously been demonstrated to be detectable in positive mode electrospray ionisation tandem mass spectrometry (ESI-MS/MS), after separation by ion-pairing reversed-phase liquid chromatography (RPLC). The separation method used tridecafluoroheptanoic acid as ion-pairing agent, and a gradient of acetonitrile for the elution of the most retained compounds. This method had previously been demonstrated to be suitable for the qualitative diagnosis of many AA disorders, and for the quantitative measurement of 16 AA in biological fluids, using their stable isotope labelled (SIL) AA as internal standard. For quantification of the other AA, an internal standard was chosen among the available SIL-AA, as close as possible to the analyte to be measured, in terms of structural analogy, and of retention time in the chromatographic system. The performances of the quantitative analysis of the other AA to be measured are reported here. They show validated results for several AA, allowing their accurate quantification, with another SIL-AA as internal standard. For some other AA, quantitative results were not accurate, allowing only semi-quantitative or qualitative determination for these parameters. PMID:16235234

  13. Modification of the metabolism and cytotoxicity of bioreductive alkylating agents by dicoumarol in aerobic and hypoxic murine tumor cells.

    Science.gov (United States)

    Keyes, S R; Rockwell, S; Sartorelli, A C

    1989-06-15

    We have demonstrated previously that dicoumarol (DIC) increased the generation of reactive metabolites from mitomycin C (MC) in EMT6 cells under hypoxic conditions in vitro. This increased reaction rate was associated with an increased toxicity of MC to hypoxic EMT6 cells. In contrast, aerobic cells treated with DIC in vitro were protected from MC toxicity. We now demonstrate that DIC sensitizes EMT6 cells to two MC analogues, porfiromycin (POR) and the 7-N-dimethylaminomethylene analogue of mitomycin C (BMY-25282), in hypoxia and protects cells from these agents in air, despite the fact that POR is preferentially toxic to hypoxic cells and BMY-25282 is preferentially toxic to aerobic cells. In contrast, DIC increases menadione cytotoxicity in both air and hypoxia and has no effect on the cytotoxicity of Adriamycin. We have also shown previously that the preferential toxicity of POR to hypoxic cells is associated with an increased rate of drug uptake. In the present study, DIC had no measurable effect on the uptake of [3H]POR but increased the extent of efflux of this agent. MC-induced DNA cross-links, which have been proposed as the lesions responsible for the lethality of MC, are decreased by DIC in air and increased by DIC in hypoxia, in concert with the observed modifications of MC cytotoxicity by DIC. However, in aerobic cells treated with DIC and MC, the decrease in DNA interstrand cross-links is not directly associated with a decrease in cytotoxicity. L1210 cells, which have no measurable quinone reductase activity, demonstrate increased toxicity when treated with DIC and MC in hypoxia, as observed with EMT6 cells. Unlike EMT6 cells, however, L1210 cells are not protected by DIC from MC toxicity in air. Taken together, these findings suggest that DIC is altering the intracellular metabolism of MC and that quinone reductase or another, unidentified, enzyme sensitive to DIC may be involved in activating MC to a toxic product in aerobic EMT6 cells. PMID:2470504

  14. Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Yadav Sapkota

    Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

  15. Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes

    Science.gov (United States)

    Ruiz-Ojeda, Francisco Javier; Gomez-Llorente, Carolina; Aguilera, Concepción María; Gil, Angel; Rupérez, Azahara Iris

    2016-01-01

    Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX) activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5) were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2) and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes. PMID:27023799

  16. Impact of 3-Amino-1,2,4-Triazole (3-AT-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Ruiz-Ojeda

    Full Text Available Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT, the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5 were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2 and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes.

  17. Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study.

    Science.gov (United States)

    Stepien, Magdalena; Duarte-Salles, Talita; Fedirko, Veronika; Floegel, Anne; Barupal, Dinesh Kumar; Rinaldi, Sabina; Achaintre, David; Assi, Nada; Tjønneland, Anne; Overvad, Kim; Bastide, Nadia; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Saieva, Calogero; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Gavrila, Diana; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Sund, Malin; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Schmidt, Julie A; Gunter, Marc; Cross, Amanda; Vineis, Paolo; Romieu, Isabelle; Scalbert, Augustin; Jenab, Mazda

    2016-01-15

    Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development. PMID:26238458

  18. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood ...

  19. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    Directory of Open Access Journals (Sweden)

    Hong SU

    2013-03-01

    determined by Western blotting. Results  The expression levels of p300, Ac-H3 and Ac-H4 protein in HG group increased, being 2.15, 1.93 and 1.87 fold of those in group NG (P<0.05, accompanying with the up-regulation of PKCβ2 protein and ROS levels in HG group. The p300, Ac-H3, Ac-H4, PKCβ2 protein expression and ROS levels in M1, M2, M3 group were higher than those in NG group, and was 1.75, 1.49, 1.47, 1.98 and 1.48 fold higher in M3 group than in NG group. The protein expressions of p300, Ac-H3 and Ac-H4 in AGEs group were increased by 1.73, 1.08 and 1.05 folds, and in AGE-M group increased by 1.47, 0.95 and 1.03 folds of that in control group (P<0.05. The protein expression levels of p300, Ac-H3 and Ac-H4 in H2O2 group increased by 1.03, 0.85 and 0.79 folds of those in control group (P<0.05. However, no significantly difference in these indices was found between H2O2-M and control groups. The protein expression levels of p300, Ac-H3 and Ac-H4 in PO group increased more obviously by 1.25, 1.06 and 1.10 folds of those in M group (P<0.05. However, the elective PKCβ2 inhibitor CGP53353 could lower those indices significantly. Conclusion  Persistent activation of transcriptional coactivator p300 and apparent modification may be normalized in HMCs. p300 may be the convergent point of glucose-induced metabolic "memory" stimulations.

  20. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism

    DEFF Research Database (Denmark)

    Galindo, C; Larsen, Mogens; Ouellet, D R;

    2015-01-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β...... AA with casein profile (AA-CN; n=5) in addition to the same basal diet. The AA-CN infusion started with half the maximal dose at 1 d in milk (DIM) and then steadily decreased from 791 to 226 g/d from DIM 2 to 29 to cover the estimated essential AA deficit. On DIM 5, 15, and 29, D[6,6-(2)H2]-glucose...... (23.7 mmol/h) was infused into a jugular vein for 5h, and 6 blood samples were taken from arterial, portal, hepatic, and mammary sources at 45-min intervals, starting 1h after the initiation of the D[6,6-(2)H2]glucose infusion. Trans-organ fluxes were calculated as veno-arterial differences times...

  1. Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice.

    Science.gov (United States)

    Fan, Yi; Zhang, Jing; Sun, Xiu-Lan; Gao, Lin; Zeng, Xiao-Ning; Ding, Jian-Hua; Cao, Cong; Niu, Ling; Hu, Gang

    2005-11-15

    Aquaporin-4 (AQP4), a predominant water channel of the brain, mediates transmembrane water movement at the blood-brain barrier and brain-cerebrospinal fluid interface. A broad pattern of evidence indicates that AQP4 and regulators of its expression are potential targets for treatment of brain swelling, but whether it participates in the regulation of neurotransmission has not been reported. We examined neurochemical differences between AQP4-knockout and wild-type mice with particular focus on neurotransmission. Basal tissue neurotransmitter and metabolite levels were measured by high-performance liquid chromatography. Significant sex- and region-specific differences of amino acids and monoamines were found in the brain of wild-type and AQP4-knockout mice. In cortex, striatum, and hippocampus of male AQP4-knockout mice, an increase of glutamine and decrease of aspartate were observed. Glutamate was increased only in female AQP4-knockout mice. The lack of AQP4 failed to affect the levels of gamma-aminobutyric acid and taurine. In the medial prefrontal cortex of AQP4-knockout mice, the levels of serotonin and norepinephrine were increased, but no significant change in dopamine level was found. In the striatum of male AQP4-knockout mice, the levels of dopamine and serotonin were remarkably increased, which was not found in female mice. In the hypothalamus of AQP4-knockout mice, only the serotonin level was altered. These results provide the first evidence that the lack of AQP4 expression is accompanied by sex- and region-specific alterations in brain amino acid and monoamine metabolism. PMID:16237719

  2. Heliothine caterpillars differ in abundance of a gut lumen aminoacylase (L-ACY-1)-Suggesting a relationship between host preference and fatty acid amino acid conjugate metabolism.

    Science.gov (United States)

    Kuhns, Emily H; Seidl-Adams, Irmgard; Tumlinson, James H

    2012-03-01

    Fatty acid amino acid conjugates (FACs) in the oral secretions of Lepidopteran larvae are responsible for eliciting plant defense responses. FACs are present despite fitness costs which suggests that they are important for larval survival. In previous work, an aminoacylase (L-ACY-1) was identified as the enzyme responsible for hydrolysis of FACs within the larvae gut. This gene is present in three related Heliothine species: Heliothis virescens, Helicoverpa zea, and Heliothis subflexa. Transcript levels in gut tissues are predictive of protein abundance and enzyme activity in the frass. H. zea has the least amount of L-ACY-1 present in gut tissue and frass, while H. virescens has intermediate protein levels and H. subflexa has the highest amount of L-ACY-1 in gut tissue as well as in frass samples. These species differ in their host range and protein intake targets, and recently, it has been shown that FACs, the substrates of L-ACY-1, are involved in nitrogen metabolism. The correlation between protein intake and degree of host range specialization suggests that this aminoacylase may allow specialized larvae to obtain nitrogen requirements despite limitations in diet heterogeneity. PMID:22266147

  3. DIABRISK - SL Prevention of cardio-metabolic disease with life style modification in young urban Sri Lankan's - study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Viberti Giancarlo

    2011-09-01

    Full Text Available Abstract Background Urban South-Asian's are predisposed to early onset of type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. There is an urgent need for country specific primary prevention strategies to address the growing burden of cardio-metabolic disease in this population. The aim of this clinical trial is to evaluate whether intensive (3-monthly lifestyle modification advice is superior to a less-intensive (12 monthly; control group lifestyle modification advice on a primary composite cardio-metabolic end point in 'at risk' urban subjects aged between 5-40 years. Methods/Design This is an open randomised controlled parallel group clinical trial performed at a single centre in Colombo, Sri-Lanka. A cluster sampling strategy was used to select a large representative sample of subjects aged between 5-40 years at high risk of T2DM and CVD for the intervention study. We have screened 23,298 (males 47% females 53% healthy subjects for four risk factors: obesity, elevated waist circumference, family history of diabetes and physical inactivity, using a questionnaire and anthropometry. Those with two or more risk-factors were recruited to the intervention trial. We aim to recruit 4600 subjects for the intervention trial. The primary composite cardio-metabolic end point is; new onset T2DM, impaired glucose tolerance, impaired fasting glycaemia, new onset hypertension and albuminuria, following 5 years of intervention. The effect of the intervention on pre-specified secondary endpoints will also be evaluated. The study will be conducted according to good clinical and ethical practice, data analysis and reporting guidelines. Discussion DIABRISK-SL is a large population based trial to evaluate the prevalence of diabetes, pre-diabetes and cardio-metabolic risk factors among young urban Sri-Lankans and the effect of a primary prevention strategy on cardio-metabolic disease end points. This work will enable country specific and regional cardio-metabolic

  4. Atomic evidence that modification of H-bonds established with amino acids critical for host-cell binding induces sterile immunity against malaria

    International Nuclear Information System (INIS)

    Based on the 3D X-ray crystallographic structures of relevant proteins of the malaria parasite involved in invasion to host cells and 3D NMR structures of High Activity Binding Peptides (HABPs) and their respective analogues, it was found that HABPs are rendered into highly immunogenic and sterile immunity inducers in the Aotus experimental model by modifying those amino acids that establish H-bonds with other HABPs or binding to host's cells. This finding adds striking and novel physicochemical principles, at the atomic level, for a logical and rational vaccine development methodology against infectious disease, among them malaria.

  5. Atomic evidence that modification of H-bonds established with amino acids critical for host-cell binding induces sterile immunity against malaria

    Energy Technology Data Exchange (ETDEWEB)

    Patarroyo, Manuel E., E-mail: mepatarr@mail.com [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad Nacional de Colombia, Bogota (Colombia); Cifuentes, Gladys [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad del Rosario, Bogota (Colombia); Pirajan, Camilo; Moreno-Vranich, Armando [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Vanegas, Magnolia [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad Nacional de Colombia, Bogota (Colombia); Universidad del Rosario, Bogota (Colombia)

    2010-04-09

    Based on the 3D X-ray crystallographic structures of relevant proteins of the malaria parasite involved in invasion to host cells and 3D NMR structures of High Activity Binding Peptides (HABPs) and their respective analogues, it was found that HABPs are rendered into highly immunogenic and sterile immunity inducers in the Aotus experimental model by modifying those amino acids that establish H-bonds with other HABPs or binding to host's cells. This finding adds striking and novel physicochemical principles, at the atomic level, for a logical and rational vaccine development methodology against infectious disease, among them malaria.

  6. Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

    Directory of Open Access Journals (Sweden)

    Hongyu Li

    Full Text Available Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

  7. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    OpenAIRE

    Su, Hong; Bo ZHOU; Ya-qian DUAN; Du, Chao

    2013-01-01

    Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3) and Ac-H4 in human renal mesangial cell (HMCs) as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d), high glucose group (HG, 25mmol/L D-glucose×2d), memory groups (M1, M2, M3, 25mmol/L...

  8. Effects of supplementation with branched-chain amino acids to low-protein diets on expression of genes related to lipid metabolism in skeletal muscle of growing pigs.

    Science.gov (United States)

    Duan, Yehui; Duan, Yangmiao; Li, Fengna; Li, Yinghui; Guo, Qiuping; Ji, Yujiao; Tan, Bie; Li, Tiejun; Yin, Yulong

    2016-09-01

    Branched-chain amino acids (BCAA), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in energy homeostasis and lipid metabolism in addition to their other functions, such as in protein metabolism. This study investigated the effects of different dietary BCAA ratios on the intramuscular fat (IMF) content and fatty acid composition in different location of skeletal muscles, including the longissimus dorsi (LD), biceps femoris (BF), and psoas major (PM) muscles of growing pigs, and also examined the mRNA expression levels of genes involved in lipid metabolism in these muscle tissues. The experiment was performed on 40 growing pigs (Large White × Landrace) with a similar initial weight (9.85 ± 0.35 kg). The pigs were randomly assigned to one of five diets: diet A was a positive control and contained 20 % crude protein (CP) with a Leu:Ile:Val ratio of 1:0.51:0.63 according to the recommendation of the National Research Council (NRC); for diets B to E, the CP level was reduced to 17 %, and the Leu:Ile:Val ratios were 1:1:1, 1:0.75:0.75, 1:0.51:0.63, and 1:0.25:0.25, respectively. No significant difference was observed in the average feed intake and feed efficiency of the pigs fed the low protein diet (17 % CP) with BCAA treatments relative to the positive control. However, there was a tendency for increased feed efficiency of the 1:0.75:0.75 group compared with the 1:1:1 group (P = 0.09). The BCAA ratio of 1:0.75:0.75 (17 % CP) increased the IMF content of BF muscle (P protein level had different effects on the fatty acid composition of the LD, BF, and PM muscles. The BCAA ratio of 1:0.51:0.63-1:0.75:0.75 (17 % CP) significantly lowered the ratio of n-6 to n-3 polyunsaturated fatty acid in these muscles compared with the positive control group (20 % CP). This effect was associated with an increase in mRNA expression levels of acetyl-CoA carboxylase, lipoprotein lipase, fatty acid transport protein, and fatty acid binding

  9. Potential protein post-translational modifications and find potential single amino acid substitutions in hepatitis B large envelope protein Posibles modificaciones postranslacionales y sustituciones de un solo aminoácido en la proteína grande de la superficie del virus de la hepatitis B

    Directory of Open Access Journals (Sweden)

    V. Wiwanitkit

    2008-03-01

    Full Text Available Post-translational modifications of proteins control many biological processes. This is also important process in virus including hepatitis B. However, there is no in-depth study on the whole hepatitis B virus large envelope protein. In this work, potential protein post-translational modifications in hepatitis B virus large envelope protein were determined by a standard bioinformatics technique. Furthermore, potential single amino acid substitutions in hepatitis B large envelope protein were also determined. It can be seen that there are possible 3 potential protein were post-translational modifications with 1 possible single substitution. This data can be useful for further study on hepatitis B virus mutant as well as planning for new vaccine production.Las modificaciones postranslacionales que sufren las proteínas controlan muchos procesos biológicos. Esto es también válido en el caso de los virus, incluyendo el de la hepatitis B. Sin embargo, no se han realizado estudios en profundidad de la totalidad de la proteína grande de superficie del virus de la hepatitis B. En el presente estudio, se han determinado las modificaciones postranslacionales que son posibles en esta proteína de la cubierta viral empleando para ello una técnica bioinformática estándar. Además, también se determinaron las sustituciones de un solo aminoácido que son posibles en la proteína grande de la superficie del virus de la hepatitis B. De este análisis podemos deducir que existen 3 posibles modificaciones translacionales en esta proteína y una potencial sustitución simple. Estos datos pueden ser útiles tanto para posteriores estudios sobre el virus mutante de la hepatitis B, como para la producción de una nueva vacuna contra este virus.

  10. Rationale and design of a proof-of-concept trial investigating the effect of uninterrupted perioperative (par)enteral nutrition on amino acid profile, cardiomyocytes structure, and cardiac perfusion and metabolism of patients undergoing coronary artery bypass grafting

    OpenAIRE

    Cocchieri Riccardo; van Venrooij Lenny MW; Niessen Hans WM; Kok Wouter EM; Verberne Hein J; Davids Mariska; Visser Marlieke; Wisselink Willem; de Mol Bas AJM; van Leeuwen Paul AM

    2011-01-01

    Abstract Background Malnutrition is very common in patients undergoing cardiac surgery. Malnutrition can change myocardial substrate utilization which can induce adverse effects on myocardial metabolism and function. We aim to investigate the hypothesis that there is a disturbed amino acids profile in the cardiac surgical patient which can be normalized by (par)enteral nutrition before, during and after surgery, subsequently improving cardiomyocyte structure, cardiac perfusion and glucose met...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-08-05

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

  12. Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells

    OpenAIRE

    Lei Zhang; Xiao-Jie Miao; Xin Wang; Hai-Hui Pan; Pu Li; Hong Ren; Yong-Rui Jia; Chuang Lu; Hong-Bing Wang; Lan Yuan; Guo-Liang Zhang

    2016-01-01

    Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine...

  13. Modification of 239Pu metabolism in the blood in various modes of iron preparation administration in the body

    International Nuclear Information System (INIS)

    A study was made of the intravenous, intraperitoneal and oral routes of iron administration. It was shown that the oral route of the entry of appropriate amounts of iron in the body made it possible to saturate the transferrin spare capacity and hence to influence 239Pu metabolism in the blood. The results obtained can be employed for improving sensitivity of indirect dosimetry methods of 239Pu in the body using chelates

  14. Self-management for obesity and cardio-metabolic fitness: Description and evaluation of the lifestyle modification program of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Coates Alison M

    2008-10-01

    Full Text Available Abstract Background Sustainable lifestyle modification strategies are needed to address obesity and cardiovascular risk factors. Intensive, individualised programs have been successful, but are limited by time and resources. We have formulated a group-based lifestyle education program based upon national diet and physical activity (PA recommendations to manage obesity and cardio-metabolic risk factors. This article describes the content and delivery of this program, with information on compliance and acceptability. Methods Overweight/obese adults (n = 153 with metabolic syndrome were recruited from the community and randomly allocated to intervention (INT or control (CON. Written copies of Australian national dietary and PA guidelines were provided to all participants. INT took part in a 16-week lifestyle program which provided a curriculum and practical strategies on 1 dietary and PA information based on national guidelines, 2 behavioural self-management tools, 3 food-label reading, supermarkets tour and cooking, 4 exercise sessions, and 5 peer-group support. Compliance was assessed using attendance records and weekly food/PA logs. Participants' motivations, perceived benefits and goals were assessed through facilitated discussion. Program acceptability feedback was collected through structured focus groups. Results Although completion of weekly food/PA records was poor, attendance at information/education sessions (77% overall and exercise participation (66% overall was high, and compared with CON, multiple markers of body composition and cardio-metabolic health improved in INT. Participants reported that the most useful program components included food-label reading, cooking sessions, and learning new and different physical exercises, including home-based options. Participants also reported finding self-management techniques helpful, namely problem solving and short-term goal setting. The use of a group setting and supportive 'peer' leaders

  15. Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

    OpenAIRE

    Qiu-Yi Wang; Yong Song; Wei Huang; Li Xiao; Qiu-Shi Wang; Gui-Mei Feng

    2016-01-01

    Background: While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Methods: Ninety-nine women with PCOS...

  16. Is the habitation of acidic-water sanctuaries by galaxiid fish facilitated by natural organic matter modification of sodium metabolism?

    Science.gov (United States)

    Glover, Chris N; Donovan, Katherine A; Hill, Jonathan V

    2012-01-01

    Acidic waters of New Zealand's West Coast are hypothesized to be a refuge for native galaxiid fish, allowing them to escape predation from acid-sensitive invasive salmonid species. To determine the mechanisms by which galaxiids tolerate low pH, we investigated sodium metabolism in inanga Galaxias maculatus in response to water pH, short-term acclimation to acidic waters, the presence and source of natural organic matter (NOM), and fish life history. Contrary to expectation, inanga were physiologically sensitive to acid exposure, displaying inhibited sodium influx and exacerbated sodium efflux. Short-term (144 h) acclimation to acid did not modify this effect, and NOM did not exert a protective effect on sodium metabolism at low pH. Inanga sourced from naturally acidic West Coast waters did, however, display a sodium influx capacity (J(max)) that was significantly elevated when compared with that of fish collected from neutral waters. All inanga, independent of source, exhibited exceptionally high sodium uptake affinities (18-40 μM) relative to previously studied freshwater teleosts. Although inanga displayed relatively poor physiological tolerance to acidic waters, their high sodium influx affinity coupled with their occupation of near-coastal waters with elevated sodium levels may permit habitation of low-pH freshwaters. PMID:22902374

  17. Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells.

    Science.gov (United States)

    Zhang, Lei; Miao, Xiao-Jie; Wang, Xin; Pan, Hai-Hui; Li, Pu; Ren, Hong; Jia, Yong-Rui; Lu, Chuang; Wang, Hong-Bing; Yuan, Lan; Zhang, Guo-Liang

    2016-01-01

    Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic. PMID:27311637

  18. Host plant-dependent metabolism of 4-hydroxybenzylglucosinolate in Pieris rapae: substrate specificity and effects of genetic modification and plant nitrile hydratase.

    Science.gov (United States)

    Agerbirk, Niels; Olsen, Carl Erik; Topbjerg, Henrik Bak; Sørensen, Jens Christian

    2007-11-01

    After ingestion of transgenic Arabidopsis thaliana CYP79A1 containing sinalbin (4-hydroxybenzylglucosinolate) due to genetic modification, only one major sinalbin-derived sulphate ester (the sulphate ester of 4-hydroxyphenylacetonitrile) was excreted by Pieris rapae caterpillars (corresponding to 69mol% of ingested sinalbin). An additional sulphate ester (the sulphate ester of 4-hydroxyphenylacetamide) was excreted when the caterpillars were reared on two plant species (Sinapis alba and Sinapis arvensis) that contained sinalbin naturally. Artificial addition of sinalbin to S. arvensis leaves resulted in increased levels of the sulphated amide, and an enzymatic activity (nitrile hydratase) explaining the formation of the sulphated amide from sinalbin was detected in both Sinapis species, but not in A. thaliana. In agreement with the suggested minor metabolic pathway, the caterpillars were able to sulphate 4-hydroxyphenylacetamide offered as part of an artificial diet. In fact, phenol and seven para-substituted phenol derivatives with substituents of moderate size were sulphated and excreted, but all tested phenols devoid of a nitrile functional group were less efficiently sulphated than the primary sinalbin detoxification product, 4-hydroxyphenylacetonitrile. This suggests that the specificity of the sulphation step involved in sinalbin metabolism may be adapted to nitriles formed as metabolites of phenolic glucosinolates. On the contrary, there was no specificity for products (4-hydroxybenzylascorbigen and 4-hydroxybenzylalcohol) derived from the semistable isothiocyanate produced from sinalbin in the absence of nitrile specifier protein. PMID:17916498

  19. The influence of straw meal on the crude protein and amino acid metabolism and the digestibility of crude nutrients in broiler hens. 3

    International Nuclear Information System (INIS)

    In two experiments with colostomized broiler hens the influence of a straw meal supplement on the apparent digestibility of the amino acids of the ration and the 15N-labelled basic amino acids in wheat was studied. In experiment 1 the animals received 120 g mixed feed plus 0, 20, 30 and 40 g straw meal per animal and day. The digestibility of the amino acids decreased on average from 86% to 83%, 80% and 79% with the growing straw intake. In contrast to the control variant, 20 g straw meal intake resulted in a singificant decrease of digestibility for lysine, histidine, glycine, tyrosine, phenylanaline, cystine and methionine. 30 and 40 g straw meal reduced significantly the digestibility of all amino acids with the exception of arginine. The amino acid composition of the crude protein in feces changed only very slightly due to the straw supplement. In experiment 2 15N-labelled wheat was a component of the ration. Of the 15N-labelled amino acids lysine, histidine and arginine, 88, 90 and 95% were apparently digested. The adaptation of the animals to straw meal intake did not change the digestibility of the amino acids. (author)

  20. Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis

    DEFF Research Database (Denmark)

    Rodriguez Prado, Edith Angelica; Kildegaard, Kanchana Rueksomtawin; Li, Mingji;

    2015-01-01

    Aromatic amino acids are precursors of numerous plant secondary metabolites with diverse biological functions. Many of these secondary metabolites are already being used as active pharmaceutical or nutraceutical ingredients, and there are numerous exploratory studies of other compounds with promi...

  1. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 10

    International Nuclear Information System (INIS)

    Over a period of 4 days 12 colostomized laying hens daily received 36 g coarse wheat meal containing 14.37 atom-% 15N excess (15N') together with a conventional ration. After the homogenisation of each oviduct N and 15N' were determined. After the precipitation with TCA the 15N' of the amino acids was analysed in both the precipitate and the supernatant. In addition, the free amino acids and the peptides were determined in the TCA soluble fraction. The atom-% 15N' in the total N and in the non-basic amino acid N showed a parallel decrease; it diminshed from 1.75 atom-% 15N' to 0.64. Of the three basic amino acids, lysine shows the lowest labelling at all four measuring points. The quotas of non-basic amino acid 14N and 15N' in the total 14N and 15N' of the oviduct are the same and amount to 53%. In contrast to this, the quota of the 14N of the basic amino acids in the total 14N of the oviduct only amounts to 21.6% and that of 15N' only to 15.4%. The average atom-% 15N' of the free amino acids 12 h after the last 15N application is 1.54 and is considerably above that of the peptides with 1.15 atom-% 15N'. 36 h after the last 15N application the ascertained value of 1.25 is identical in both fractions. The labelling of the free amino acids decreases more quickly than that of the peptides the more time has passed after the last 15N application. (author)

  2. Metabolic profile modifications in milk after enrofloxacin administration studied by liquid chromatography coupled with high resolution mass spectrometry.

    Science.gov (United States)

    Junza, A; Saurina, J; Barrón, D; Minguillón, C

    2016-08-19

    High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. PMID:27425761

  3. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 7

    International Nuclear Information System (INIS)

    In a 15N labelling experiment 12 colostomized laying hens received 15N-labelled wheat with 14.37 atom-% 15N excess (15N') over 4 days. 3 hens each were butchered after 12 h, 36 h, 60 h and 108 h after the last 15N' application. The gastrointestinal tract was divided into 3 parts (esophagus with crop and gizzard as well as glandular stomach, small intestine, large intestine). These parts and the pancreas were hydrolyzed with 6 N HCl and the individual basic as well as the sum of acid and neutral amino acids were determined in the hydrolyzed fractions. In addition, the amino acids and peptides were determined in the TCA soluble N fraction. The atom-% 15N' was determined in the individual amino acid and peptide fractions. The labelling of the basic amino acids in the individual tract segments was lower than in the acid and neutral amino acids. In comparison to the peptides, a higher atom-% 15N' could be determined in the free amino acids. (author)

  4. Posttranslational modifications of FERREDOXIN-NADP+ OXIDOREDUCTASE in Arabidopsis chloroplasts.

    Science.gov (United States)

    Lehtimäki, Nina; Koskela, Minna M; Dahlström, Käthe M; Pakula, Eveliina; Lintala, Minna; Scholz, Martin; Hippler, Michael; Hanke, Guy T; Rokka, Anne; Battchikova, Natalia; Salminen, Tiina A; Mulo, Paula

    2014-12-01

    Rapid responses of chloroplast metabolism and adjustments to photosynthetic machinery are of utmost importance for plants' survival in a fluctuating environment. These changes may be achieved through posttranslational modifications of proteins, which are known to affect the activity, interactions, and localization of proteins. Recent studies have accumulated evidence about the crucial role of a multitude of modifications, including acetylation, methylation, and glycosylation, in the regulation of chloroplast proteins. Both of the Arabidopsis (Arabidopsis thaliana) leaf-type FERREDOXIN-NADP(+) OXIDOREDUCTASE (FNR) isoforms, the key enzymes linking the light reactions of photosynthesis to carbon assimilation, exist as two distinct forms with different isoelectric points. We show that both AtFNR isoforms contain multiple alternative amino termini and undergo light-responsive addition of an acetyl group to the α-amino group of the amino-terminal amino acid of proteins, which causes the change in isoelectric point. Both isoforms were also found to contain acetylation of a conserved lysine residue near the active site, while no evidence for in vivo phosphorylation or glycosylation was detected. The dynamic, multilayer regulation of AtFNR exemplifies the complex regulatory network systems controlling chloroplast proteins by a range of posttranslational modifications, which continues to emerge as a novel area within photosynthesis research. PMID:25301888

  5. D-Serine metabolism in C6 glioma cells: Involvement of alanine-serine-cysteine transporter (ASCT2) and serine racemase (SRR) but not D-amino acid oxidase (DAO)

    OpenAIRE

    Sikka, Pilleriin; Walker, Rosie; Cockayne, Rebecca; Wood, Matthew JA; Harrison, Paul J; Burnet, Philip WJ

    2010-01-01

    D-serine is an endogenous N-methyl-D-aspartate (NMDA) receptor coagonist. It is synthesized from L-serine by serine racemase (SRR), but many aspects of its metabolism remain unclear, especially in the forebrain, which lacks active D-amino acid oxidase (DAO), the major D-serine degradative enzyme. Candidate mechanisms include SRR operating in α,β-eliminase mode (converting D-serine to pyruvate) and regulation by serine transport, in which the alanine-serine-cysteine transporter ASCT2 is implic...

  6. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 9

    International Nuclear Information System (INIS)

    Over 4 days 12 colostomized laying hens received 36 g coarse wheat meal with a 15N excess (15N') of 14.37 atom-% together with a conventional diet. The labelling of lysine amounted to 13.58 atom-% 15N', that of histidine to 14.38 and of arginine to 13.63 atom-% 15N'. Three animals each were butchered 12 h, 36 h, 60 h and 108 h after the last 15N application. In the two charges of follicles (above and below 25 g) N and 15N' were determined in the individual basic amino acids as well as their sum in the non-basic ones. The atom-% 15N' was determined in the TCA soluble fraction of the free amino acid and peptide fractions. The average atom-% 15N' of the big follicles is 12 and 36 h after the last 15N application lower, and higher at the last two measuring points than that of the medium and small follicles. The atom-% of the total nitrogen and of the non-basic amino acids was significantly higher in both the bigger and the smaller follicles than in the basic amino acids. 70% of the heavy nitrogen in the total 15N' of the big follicles could be detected in amino acids; its quota in the small follicles was 67%. (author)

  7. Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications

    DEFF Research Database (Denmark)

    Otero, José Manuel; Vongsangnak, Wanwipa; Asadollahi, Mohammadali;

    2010-01-01

    BACKGROUND: The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where...... SNPs are distributed across 158 metabolic genes, with 85 of the SNPs being nonsynonymous (e.g., encoding amino acid modifications). Amongst metabolic SNPs detected, there was pathway enrichment in the galactose uptake pathway (GAL1, GAL10) and ergosterol biosynthetic pathway (ERG8, ERG9). Physiological...

  8. Daily balance of leaf sugars and amino acids as indicators of common bean (Phaseolus vulgaris L.) metabolic response and drought intensity

    OpenAIRE

    Santos, Mauro Guida; Pimentel, Carlos

    2009-01-01

    Leaf soluble sugar, starch and free amino acid amounts were evaluated in two bean genotypes, Carioca and Ouro Negro, grown in 10 L pots in a greenhouse. This was realized during a single day for Carioca and during ten days of water deficit for both genotypes, at 06:00 and 18:00 h. During the day, an increase in all parameters occurred up to midday, while in the afternoon, carbohydrate amounts varied in opposition to amino acids amounts. Under water deficit, the leaf soluble sugars at 18:00 an...

  9. Microdialysis with radiometric monitoring of L-[β-11C]DOPA to assess dopaminergic metabolism: effect of inhibitors of L-amino acid decarboxylase, monoamine oxidase, and catechol-O-methyltransferase on rat striatal dialysate.

    Science.gov (United States)

    Okada, Maki; Nakao, Ryuji; Hosoi, Rie; Zhang, Ming-Rong; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Inoue, Osamu

    2011-01-01

    The catecholamine, dopamine (DA), is synthesized from 3,4-dihydroxy-L-phenylalanine (L-DOPA) by aromatic L-amino acid decarboxylase (AADC). Dopamine metabolism is regulated by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). To measure dopaminergic metabolism, we used microdialysis with radiometric detection to monitor L-[β-(11)C]DOPA metabolites in the extracellular space of the rat striatum. We also evaluated the effects of AADC, MAO, and COMT inhibitors on metabolite profiles. The major early species measured after administration of L-[β-(11)C]DOPA were [(11)C]3,4-dihydroxyphenylacetic acid ([(11)C]DOPAC) and [(11)C]homovanillic acid ([(11)C]HVA) in a 1:1 ratio, which shifted toward [(11)C]HVA with time. An AADC inhibitor increased the uptake of L-[β-(11)C]DOPA and L-3-O-methyl-[(11)C]DOPA and delayed the accumulation of [(11)C]DOPAC and [(11)C]HVA. The MAO and COMT inhibitors increased the production of [(11)C]3-methoxytyramine and [(11)C]DOPAC, respectively. These results reflect the L-DOPA metabolic pathway, suggesting that this method may be useful for assessing dopaminergic metabolism. PMID:20407462

  10. Co-ordinated research programme on application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report on the second research co-ordination meeting

    International Nuclear Information System (INIS)

    The use of isotopes has revolutionized the field of human nutrition research, but has been of greatest benefit to industrialized countries. The International Atomic Energy Agency is sponsoring programmes using isotopic and related technologies in human nutrition research to address issues that are of priority to developing countries. Scientists participating in the Coordinated Research Programme (CRP) on ''Amino Acid and Protein Metabolism in Malnourished Populations of Developing Countries'' are conducting research on the interaction between infection and amino acid metabolism, particularly the potential diversion of substrates from anabolic pathways to fight infection in marginally nourished children during periods of infections. This topic is of great importance to the nutritional status of children in developing countries, who frequently or chronically have infections and who, as a consequence, may have alterations in nutrient requirements. The CRP has developed and implemented a standardized protocol for measuring leucine oxidation during infection in 8 different countries. The CRP is expected to contribute important new knowledge about interactions between protein utilization, the stresses of unhygienic environments, and infections in marginally nourished people. This information is expected to be applicable to efforts to increase efficient utilization of limited food resources in developing countries. Another highlight of the CRP is that it represents an international team of nutrition scientists who together are building nutritional biology research capabilities in developing countries. Refs, figs, tabs

  11. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 11

    International Nuclear Information System (INIS)

    Over a period of 4 days 12 colostomized laying hens daily received 36 g 15N-labelled wheat with 15N excess (15N') of 14.37 atom-% together with a conventional feed mixture for laying hens. The labelling of the lysine N in the wheat was 13.58 atom-%, that of histidine N 14.38 and that of arginine 15N' 13.63 atom-% 15N'. Three hens each were butchered 12, 36, 60 and 108 h after the last 15N' feeding. The first three hens did not receive any feed before being butchered. The following three hens each received the unlabelled feed ration for another 1, 2 or 4 days, resp., after the main period until they were butchered. The total of skeleton muscles, heart and stomach muscle (without inner skin) of each hen were combined into one sample, cut thinly, drenched with fluid nitrogen and pulverized. N, 15N' and the basic and non-basic amino acids as well as their 15N' were determined in the individual samples. In contrast to the organs, the proteins in the muscle tissue have a long half-life so that a slight decrease of atom-% 15N' in the muscles could only be detected after 108 h. The 14N and 15N' quota of the non-basic amino acids in the total nitrogen of the muscles is 50 %. The 14N quota of the basic amino acids is 30% and the 15N' quota only 22.5% in the total muscle N. The heavy nitrogen of the free lysine in the TCA soluble N fraction is hardly detectable 36 h and 60 h after the last 15N' supply and not at all after 108 h. In contrast to this, the other two free basic amino acids remain significantly higher labelled in dependence on the last butchering time. (author)

  12. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 2

    International Nuclear Information System (INIS)

    Over 4 days 12 colostomized laying hens received toghether with a commercial ration labelled wheat with a 15N excess (15N') of 14.37 atom-%. The labelling of the basic amino acids amounted to 13.58 atom-% for lysine, to 14.38 atom-% for histidine and to 13.63 atom-% 15N' for arginine. 3 animals each were butchered 12 h, 36 h, 60 h and 108 h, resp. after the last application of 15N. The heavy nitrogen in the total N and in the N fraction of non-protein origin as well as in the basic amino acids in feces was daily determined for the individual hens in the total experimental period. On average the crude protein of feces contained 5.45% lysine, 2.32% histidine and 3.68% arginine: the protein of feces correspondingly contained 5.43% lysine, 2.32% histidine and 4.07% arginine. The quota of TCA-soluble N in the total N of feces amounts to one third on the 3rd and 4th days of the experiment and that of 15N' to 28%. The average atom-% 15N' of the protein fraction is 3.48 atom-% 15N' and that of the non-protein N fraction of feces 2.93 atom-% 15N'. The apparent digestibility of the 14N of the ration on average amounts to 82.8% and that of the wheat 15N' to 87.5%. The average quota of the basic amino acids in the protein compounds of feces amounts to 70.9% for lysine 15N', 73.7% for histidine 15N' and 70.3% for arginine 15N'. The digestibility of the 15N-labelled amino acids amounts to 80.4% for lysine, 90.8% for histidine and 90.2% for arginine. (author)

  13. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 4

    International Nuclear Information System (INIS)

    12 colostomized laying hybrids with an 81% laying performance received 36 g wheat containing a 15N excess (15N') of 14.37 atom-% in a customary ration over 4 days. The wheat lysine contained 13.58 atom-% 15N', histidine 14.38 and arginine 13.63 atom-% 15N'. In the 4-day period of 15N' application 540 mg 15N', 18.1 mg lysine 15N', 21.5 mg histidine 15N' and 47.9 mg arginine 15N' were consumed per hen. Subsequently the animals received the same ration with unlabelled wheat. 12 h, 36 h, 60 h and 108 h after the last 15N' application 3 animals each were butchered. The atom-% 15N' of the lysine was below that of the two other basic and of the non-basic amino acids. The labelling of the amino acids of the egg white decreased rapidly 2 days after 15N' application. The atom-% of the 15N' of the yolk of egg, however, increased after the discontinuation and remained the same for 4 days after the last 15N' application. The 14N and 15N' amounts measured in the complete experiment period are distributed over the 3 basic and the 12 non-basic (excluding thioamino acids) amino acids in the white of egg for 14N as 25.0%:57.6% and for 15N' as 18.2%:57.5%. In the yolk of egg 28.5% 14N for the basic and 56.8% for the non-basic amino acids could be calculated; the corresponding values for 15N' were 17.8% and 55.5%. (author)

  14. Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis.

    Science.gov (United States)

    Rodriguez, Angelica; Kildegaard, Kanchana R; Li, Mingji; Borodina, Irina; Nielsen, Jens

    2015-09-01

    Aromatic amino acids are precursors of numerous plant secondary metabolites with diverse biological functions. Many of these secondary metabolites are already being used as active pharmaceutical or nutraceutical ingredients, and there are numerous exploratory studies of other compounds with promising applications. p-Coumaric acid is derived from aromatic amino acids and, besides being a valuable chemical building block, it serves as precursor for biosynthesis of many secondary metabolites, such as polyphenols, flavonoids, and some polyketides. Here we developed a p-coumaric acid-overproducing Saccharomyces cerevisiae platform strain. First, we reduced by-product formation by knocking out phenylpyruvate decarboxylase ARO10 and pyruvate decarboxylase PDC5. Second, different versions of feedback-resistant DAHP synthase and chorismate mutase were overexpressed. Finally, we identified shikimate kinase as another important flux-controlling step in the aromatic amino acid pathway by overexpressing enzymes from Escherichia coli, homologous to the pentafunctional enzyme Aro1p and to the bifunctional chorismate synthase-flavin reductase Aro2p. The highest titer of p-coumaric acid of 1.93 ± 0.26 g L(-1) was obtained, when overexpressing tyrosine ammonia-lyase TAL from Flavobacterium johnsoniaeu, DAHP synthase ARO4(K229L), chorismate mutase ARO7(G141S) and E. coli shikimate kinase II (aroL) in Δpdc5Δaro10 strain background. To our knowledge this is the highest reported titer of an aromatic compound produced by yeast. The developed S. cerevisiae strain represents an attractive platform host for production of p-coumaric-acid derived secondary metabolites, such as flavonoids, polyphenols, and polyketides. PMID:26292030

  15. In Ovo administration of silver nanoparticles and/or amino acids influence metabolism and immune gene expression in chicken embryos

    DEFF Research Database (Denmark)

    Bhanja, Subrat K.; Hotowy, Anna Malgorzata; Mehra, Manish;

    2015-01-01

    heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control...... embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, Nano......, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2) expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4) expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that Nano...

  16. Metabolic cleavage of N- and C-terminal amino acids of an insect oostatic peptide H-Tyr-Asp-Pro-Ala-Pro-OH

    Czech Academy of Sciences Publication Activity Database

    Tykva, Richard; Slaninová, Jiřina; Bennettová, Blanka; Hlaváček, Jan; Černý, B.; Vlasáková, Věra; Němec, Václav

    Praha : Ústav organické chemie a biochemie AV ČR, 2005 - (Slaninová, J.), s. 100-102 ISBN 80-86241-26-2. - (Collection Symposium Series. 8). [Biologically Active Peptides /9./. Praha (CZ), 20.04.2005-22.04.2005] R&D Projects: GA ČR(CZ) GA203/02/0247 Institutional research plan: CEZ:AV0Z40550506 Keywords : oostatic peptides * radiolabeling * metabolic cleavage Subject RIV: CE - Biochemistry

  17. Metabolic enzymes link morphine withdrawal with metabolic disorder

    Institute of Scientific and Technical Information of China (English)

    Xi Jiang; Jing Li; Lan Ma

    2007-01-01

    @@ Energy metabolism is a fundamental biological process that is vital for the survival of all species. Disorders in the metabolic system result in deficiency or redundancy of certain nutrients, including carbohydrates, lipids, amino acids, etc. Abnormality of the energy metabolism system leads to a number of metabolic diseases, such as the metabolic syndrome. Broadly speaking, the term "metabolic diseases" now tends to be widened to the category that refers to all diseases with metabolism disorder.

  18. Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

    Science.gov (United States)

    Wang, Qiu-Yi; Song, Yong; Huang, Wei; Xiao, Li; Wang, Qiu-Shi; Feng, Gui-Mei

    2016-01-01

    Background: While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Methods: Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial. Participants were randomized into two groups such as DRP-containing COCs, and CPA-containing COCs. Participants took COCs cyclically for 6 months, combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise). Clinical measures and biochemical and hormone profiles were compared. Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests. The Wilcoxon signed rank test was used when the data were not normally distributed. Analysis of covariance was used to control for age, body mass index (BMI), and baseline data of each analyzed parameter when compared between the two groups. Results: A total of 68 patients have completed the study. The combination regimen of COCs, metformin, and lifestyle modifications in these patients resulted in a significant decrease in BMI, acne, and hirsutism scores when compared to baseline levels in both groups (P PCOS and metabolic disorders compared with CPA-containing COCs. Trial Registration: Chinese Clinical Trial Registry, ChiCTR-TRC-11001143; http://www.chictr.org.cn/showproj.aspx?proj=8395. PMID:27064030

  19. Enhanced antibody production associated with altered amino acid metabolism in a hybridoma high-density perfusion culture established by gravity separation.

    Science.gov (United States)

    Hansen, H A; Damgaard, B; Emborg, C

    1993-01-01

    A high density hybridoma perfusion culture was established by separating and recycling cells from the product stream to the reactor using a simple external sedimentation-based separator-an inclined modified Erlenmeyer flask. After 3 weeks, when the optimal perfusion rate of 1.0 day-1 had been reached, viable cell density stabilized at around 10 x 10(6) cells ml-1, a level five times that obtained by simple batch culture. The efficiency of the separator was enhanced by cell flocculation. Specific antibody productivity, which was initially 0.4 micrograms 1 x 10(6) cells-1 h-1, decreased to half that value while cell density was increasing, but recovered to the initial level when the culture finally stabilized at a high cell density. During the final phase, when viable cell density and specific antibody production were high, there was a marked shift in metabolism. Consumption of the two most important substrates for energy generation, glucose and glutamine, caused their broth concentrations to decrease to 1.5 mM and 1 mM, respectively, from input medium concentrations of 25 mM and 10 mM, respectively. At the same time there was an increase in the specific production of glycine and aspartate, their broth concentrations reaching 1.5 mM and 0.02 mM, respectively. We suggest that this shift in metabolism results in enhanced production of ATP from glutamine. The specific glucose consumption and lactate production also indicate that there is a shift to more energy efficient metabolism. The mechanism whereby this leads to enhanced specific antibody production remains to be elucidated. Nevertheless, the combination of high cell density and enhanced productivity obtained with the present perfusion culture resulted in a high monoclonal antibody production-100 mg 1-1 d-1. PMID:7763691

  20. 3-(3-amino-3-carboxypropyl)-5,6-Dihydrouridine is one of two novel post-transcriptional modifications in tRNALys(UUU) from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Español, Yaiza; Giessing, Anders M B;

    2011-01-01

    tRNA is the most heavily modified of all RNA types, with typically 10-20% of the residues being post-transcriptionally altered. Unravelling the modification pattern of a tRNA is a challenging task; there are 92 currently known tRNA modifications [1], many of which are chemically similar....... Furthermore, the tRNA has to be investigated with single-nucleotide resolution in order to ensure complete mapping of all modifications. In the present work, we characterized tRNA(Lys) (UUU) from Trypanosoma brucei, and provide a complete overview of its post-transcriptional modifications. The first step was...... MALDI-TOF MS of two independent digests of the tRNA, with RNase A and RNase T1, respectively. This revealed digestion products harbouring mass-changing modifications. Next, the modifications were mapped at the nucleotide level in the RNase products by tandem MS. Comparison with the sequence of the...

  1. 6th Amino Acid Assessment Workshop

    Science.gov (United States)

    The focus of the 6th workshop is on lysine, arginine, and related amino acids. Functions, metabolic pathways, clinical uses, and upper tolerance intakes are emphasized in the articles that follow. Lysine is arguably the most deficient amino acid in the food supply of countries where poverty exists, ...

  2. The influence of straw meal on the crude protein and amino acid metabolism and the digestibility of crude nutrients in broiler breeding hens. 1

    International Nuclear Information System (INIS)

    The metabolization of the straw N and the influence of the straw on N excretion in urine were studied in 2 experiments with colostomized broiler hens and with 15N-labelled wheat straw as well as 15N-labelled wheat. In experiment 1 the test animals divided up into 4 groups received 0 g, 20 g, 30 g and 40 g straw meal per animal and day in addition to 120 g mixed feed. The daily 15N excess (15N') intake from the straw was 18.4 mg, 27.5 mg and 36.7 mg. The amount of 15N' daily consumed with the labelled wheat in experiment 2 was 119.7 mg. 40 g straw meal resulted in a significantly increased amount of urine (p 15N' of the labelled wheat was not influenced by the straw meal supplement. The productive 15N' of the straw increased from 3.8 mg/animal and day (20 g straw) to 13.4 mg/animal and day (40 g straw). In contrast to 15N wheat, straw as a 15N source resulted in a lower labelling of uric acid N in comparison with urine N. It can be assumed that the changed metabolization of the straw N is influenced by microbial processes in the intestines. (author)

  3. Postprandial fate of amino acids: adaptation to molecular forms

    OpenAIRE

    Nolles, J.A.

    2006-01-01

    During the postprandial phase dietary proteins are digested to peptides and amino acids and absorbed. Once absorbed the peptides are further hydrolyzed to amino acids and transported to the tissues. These amino acids are largely incorporated into body proteins. Not all amino acids are, however, incorporated into body proteins part of these amino acids are oxidized, and can, thus, no longer be utilized to support protein metabolism in the body. The objective of this thesis was to increase the ...

  4. D-amino carboxamide-based recruitment of dinitrophenol antibodies to bacterial surfaces via peptidoglycan remodeling.

    Science.gov (United States)

    Fura, Jonathan M; Pires, Marcos M

    2015-07-01

    During the past few decades there has been a rapid emergence of multidrug resistant bacteria afflicting human patients. At the same time, reduced output from pharmaceutical industry in this area precipitated a sharp decrease in the approval of new antibiotics. The combination of these factors potentially compromises the ability to effectively combat bacterial infections. While traditional drug discovery efforts continue in the pursuit of small molecule agents that disrupt bacterial growth, non-traditional efforts could serve to complement antimicrobial strategies. We recently demonstrated our ability to remodel the surface of bacterial cells using unnatural D-amino acids displaying the antigenic dinitrophenyl (DNP) handle. These immune stimulant D-amino acids derivatives were metabolically incorporated onto the peptidoglycan of bacteria via a promiscuous surface-anchored transpeptidase. The covalent modification of DNP moieties onto the peptidoglycan led to the anti-DNP antibody opsonization of the bacterial cell surface. Herein, we show that the amidation of the C-terminus to generate DNP-displaying D-amino carboxamide drastically improves antibody recruitment. Antibody opsonization using the D-amino carboxamide agent is observed at lower concentrations than the D-amino acid counterpart. In addition, the recruitment of endogenous antibodies in pooled human serum to the DNP-modified bacterial cell surface is demonstrated for the first time. We envision that the C-terminus amidation of DNP-conjugated D-amino acids could potentially facilitate translation of these results to in vivo animal disease models. PMID:25653048

  5. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 5

    International Nuclear Information System (INIS)

    12 colostomized laying hens which received 15N-labelled wheat over 4 days were butchered 12 h, 36 h, and 108 h (3 animals each) after the last 15N application. The intake of 15N exess (15N') from the wheat amounted to 540 mg 15N' during the application period. The 15N' in the blood plasma decreased after the last 15N' application from 0.76 atom-% to 0.55 atom-% after 108 h, the labelling of the corpuscular components at the same measuring points increased from 0.28 to 0.50 atom-% 15N'. 96.6% of the plasma 15N' and 93,8% of that in the corpuscles is precipitable in trichloroacetic acid. The atom-% 15N' of histidine in the total blood remained unchanged in dependence on the butchering time. The 15N amount in lysine and arginine and that in the non-basic amino acids decreased inconsiderably in the period between 12 h and 108 h after the last 15N' wheat feeding. (author)

  6. Branched-Chain Amino Acids

    Directory of Open Access Journals (Sweden)

    Matteo Ghiringhelli

    2015-07-01

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

  7. Posttranslational Modifications of FERREDOXIN-NADP+ OXIDOREDUCTASE in Arabidopsis Chloroplasts1[W][OPEN

    Science.gov (United States)

    Lehtimäki, Nina; Koskela, Minna M.; Dahlström, Käthe M.; Pakula, Eveliina; Lintala, Minna; Scholz, Martin; Hippler, Michael; Hanke, Guy T.; Rokka, Anne; Battchikova, Natalia; Salminen, Tiina A.; Mulo, Paula

    2014-01-01

    Rapid responses of chloroplast metabolism and adjustments to photosynthetic machinery are of utmost importance for plants’ survival in a fluctuating environment. These changes may be achieved through posttranslational modifications of proteins, which are known to affect the activity, interactions, and localization of proteins. Recent studies have accumulated evidence about the crucial role of a multitude of modifications, including acetylation, methylation, and glycosylation, in the regulation of chloroplast proteins. Both of the Arabidopsis (Arabidopsis thaliana) leaf-type FERREDOXIN-NADP+ OXIDOREDUCTASE (FNR) isoforms, the key enzymes linking the light reactions of photosynthesis to carbon assimilation, exist as two distinct forms with different isoelectric points. We show that both AtFNR isoforms contain multiple alternative amino termini and undergo light-responsive addition of an acetyl group to the α-amino group of the amino-terminal amino acid of proteins, which causes the change in isoelectric point. Both isoforms were also found to contain acetylation of a conserved lysine residue near the active site, while no evidence for in vivo phosphorylation or glycosylation was detected. The dynamic, multilayer regulation of AtFNR exemplifies the complex regulatory network systems controlling chloroplast proteins by a range of posttranslational modifications, which continues to emerge as a novel area within photosynthesis research. PMID:25301888

  8. Chemical modification of L-glutamine to alpha-amino glutarimide on autoclaving facilitates Agrobacterium infection of host and non-host plants: A new use of a known compound

    Directory of Open Access Journals (Sweden)

    Das Pralay

    2011-05-01

    Full Text Available Abstract Background Accidental autoclaving of L-glutamine was found to facilitate the Agrobacterium infection of a non host plant like tea in an earlier study. In the present communication, we elucidate the structural changes in L-glutamine due to autoclaving and also confirm the role of heat transformed L-glutamine in Agrobacterium mediated genetic transformation of host/non host plants. Results When autoclaved at 121°C and 15 psi for 20 or 40 min, L-glutamine was structurally modified into 5-oxo proline and 3-amino glutarimide (α-amino glutarimide, respectively. Of the two autoclaved products, only α-amino glutarimide facilitated Agrobacterium infection of a number of resistant to susceptible plants. However, the compound did not have any vir gene inducing property. Conclusions We report a one pot autoclave process for the synthesis of 5-oxo proline and α-amino glutarimide from L-glutamine. Xenobiotic detoxifying property of α-amino glutarimide is also proposed.

  9. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a northern european family population

    OpenAIRE

    Zhang, Yi; Kent, Jack W; Lee, Adam; Cerjak, Diana; ALI Omar; Diasio, Robert; Olivier, Michael; Blangero, John; Carless, Melanie A.; Kissebah, Ahmed H.

    2013-01-01

    Background Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated w...

  10. ‘Red Ruby’: an interactive web-based intervention for lifestyle modification on metabolic syndrome: a study protocol for a randomized controlled trial

    OpenAIRE

    Jahangiry, Leila; Shojaeizadeh, Davoud; Najafi, Mahdi; Mohammad, Kazem; Abbasalizad Farhangi, Mahdieh; MONTAZERI, Ali

    2014-01-01

    Background Although effectiveness of web-based interventions on lifestyle changes are recognized, the potential of such programs on metabolic syndrome has not been explored. We describe the protocol of a randomized controlled trial that aims to determine the feasibility, acceptability, usability, and effectiveness of interactive technology on lifestyle intervention in a population with metabolic syndrome. Methods/design This is a two-arm randomized controlled trial. The study includes 160 par...

  11. Metabolic microspheres

    Science.gov (United States)

    Fox, Sidney W.

    1980-08-01

    A systematic review of catalytic activities in thermal proteinoids and microspheres aggregated therefrom yields some new inferences on the origins and evolution of metabolism. Experiments suggest that, instead of being inert, protocells were already biochemically and cytophysically competent. The emergence and refinement of metabolism ab initio is thus partly traced conceptually. When the principle of molecular self-instruction, as of amino acids in peptide synthesis, is taken into account as a concomitant of natural selection, an expanded theory of organismic evolution, including saltations, emerges.

  12. Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment

    Science.gov (United States)

    Hu, Hong; Bai, Xi; Shah, Assar Ali; Dai, Sifa; Wang, Like; Hua, Jinling; Che, Chuanyan; He, Shaojun; Wen, Aiyou; Jiang, Jinpeng

    2016-06-01

    The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased ( P glutamine synthetase (GS) and gamma-aminobutyric acid transaminase (GABA-T) at 28, 35, and 42 days. Dietary Gln and GABA improved ( P < 0.05) DWG and DFC of broilers under cyclic HS during 28-42 days. In breast muscle, the Gln supplementation increased ( P < 0.05) the concentrations of Gln (28, 35, and 42 days), Glu (28, 35, and 42 days), and GABA (42 days) and the activities of glutaminase (28, 35, and 42 days) and GAD (28, 35, and 42 days) but decreased ( P < 0.05) GS activities at 28, 35, and 42 days and GABA-T activities at 28 days. The addition of GABA increased ( P < 0.05) the concentrations of Gln and Glu and activities of glutaminase and GAD, while it decreased ( P < 0.05) GABA-T activities at 28, 35, and 42 days. Significant interactions ( P < 0.05) between Gln and GABA were found on breast skeletal muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA metabolism of broilers.

  13. Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment

    Science.gov (United States)

    Hu, Hong; Bai, Xi; Shah, Assar Ali; Dai, Sifa; Wang, Like; Hua, Jinling; Che, Chuanyan; He, Shaojun; Wen, Aiyou; Jiang, Jinpeng

    2015-10-01

    The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased (P glutamine synthetase (GS) and gamma-aminobutyric acid transaminase (GABA-T) at 28, 35, and 42 days. Dietary Gln and GABA improved (P < 0.05) DWG and DFC of broilers under cyclic HS during 28-42 days. In breast muscle, the Gln supplementation increased (P < 0.05) the concentrations of Gln (28, 35, and 42 days), Glu (28, 35, and 42 days), and GABA (42 days) and the activities of glutaminase (28, 35, and 42 days) and GAD (28, 35, and 42 days) but decreased (P < 0.05) GS activities at 28, 35, and 42 days and GABA-T activities at 28 days. The addition of GABA increased (P < 0.05) the concentrations of Gln and Glu and activities of glutaminase and GAD, while it decreased (P < 0.05) GABA-T activities at 28, 35, and 42 days. Significant interactions (P < 0.05) between Gln and GABA were found on breast skeletal muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA metabolism of broilers.

  14. Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors

    Directory of Open Access Journals (Sweden)

    Naoyuki eSato

    2013-11-01

    Full Text Available It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD. Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of 1 compromised vascular reactivity, 2 vascular lesions, 3 hypo/hyperglycemia, and 4 exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. Beta-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: 1 functional MRI or SPECT for cerebrovascular reactivity, 2 MRI for ischemic lesions and atrophy, 3 clinical episodes of hypoglycemia and hyperglycemia, 4 amyloid-PET and tau-PET for pathological features of AD, would be required.

  15. Comparison of Drospirenone-with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

    Institute of Scientific and Technical Information of China (English)

    Qiu-Yi Wang; Yong Song; Wei Huang; Li Xiao; Qiu-Shi Wang; Gui-Mei Feng

    2016-01-01

    Background:While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS),comparative data regarding metabolic effects of different progestogens on this patient population are missing.This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs,combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders.Methods:Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial.Participants were randomized into two groups such as DRP-containing COCs,and CPA-containing COCs.Participants took COCs cyclically for 6 months,combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise).Clinical measures and biochemical and hormone profiles were compared.Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests.The Wilcoxon signed rank test was used when the data were not normally distributed.Analysis of covariance was used to control for age,body mass index (BMI),and baseline data of each analyzed parameter when compared between the two groups.Results:A total of 68 patients have completed the study.The combination regimen of COCs,metformin,and lifestyle modifications in these patients resulted in a significant decrease in BMI,acne,and hirsutism scores when compared to baseline levels in both groups (P < 0.05).Blood pressure (BP) was significantly different in the CPA group when compared to baseline (75.14 ± 6.77 mmHg vs.80.70 ± 5.60 mmHg,P < 0.01),and after 6 months of treatment,only the change in systolic BP was significantly different between the two groups (4.00 [-6.00,13.00] mmHg vs.-3.50 [-13.00,9.00] mmHg,P =0.009).Fasting glucose,fasting insulin,and homeostasis model assessment-insulin resistance decreased significantly in the DRP group (5.40 ± 0.41 mmol

  16. Plasma amino acids

    Science.gov (United States)

    Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

  17. Plasma amino acids

    Science.gov (United States)

    Plasma amino acids is a screening test done on infants that looks at the amounts of amino ... Laboratory error High or low amounts of individual plasma amino acids must be considered with other information. ...

  18. Modification of the liver fatty acids by Hibiscus sabdariffa Linnaeus (Malvaceae) infusion, its possible effect on vascular reactivity in a metabolic syndrome model.

    Science.gov (United States)

    Pérez-Torres, Israel; Zúñiga Muñoz, Alejandra; Beltrán-Rodríguez, Ulises; Díaz-Díaz, Eulises; Martínez-Memije, Raúl; Guarner Lans, Verónica

    2014-01-01

    We investigated the effects of Hibiscus sabdariffa Linnaeus (HSL)-fed infusion on the fatty acid (FA) profile in liver of metabolic syndrome (MS) rats and its possible effect on vascular reactivity. Body mass, intra-abdominal fat, triglycerides, insulin, blood pressure, saturated, monounsaturated FA, NEFAs, Δ(9)-, Δ(6)-desaturases and vasoconstriction were increased, while vasorelaxation, polyunsaturated FA, endothelial nitric oxide and [Formula: see text]/[Formula: see text] ratio decreased in MS versus Control, but HSL infusion modified it and increased Δ(5)-desaturase. The results suggest that the alteration in FA liver metabolism in the MS contributes to impaired vascular reactivity, but treatment with of HSL infusion can improve this condition. PMID:23734849

  19. Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

    OpenAIRE

    Li, Hongyu; bu, Qian; Chen, Bo; Shao, Xue; Hu, Zhengtao; Deng, Pengchi; LV, LEI; Deng, Yi; Zhu, Ruiming; LI Yan; Zhang, Baolai; Hou, Jing; Du, Changman; Zhao, Qian; Fu, Dengqi

    2014-01-01

    Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned ...

  20. Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription

    OpenAIRE

    Allison, David F.; Wamsley, J. Jacob; Kumar, Manish; Li, Duo; Gray, Lisa G.; Hart, Gerald W.; David R Jones; Mayo, Marty W.

    2012-01-01

    The molecular mechanisms linking glucose metabolism with active transcription remain undercharacterized in mammalian cells. Using nuclear factor-κB (NF-κB) as a glucose-responsive transcription factor, we show that cells use the hexosamine biosynthesis pathway and O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) to potentiate gene expression in response to tumor necrosis factor (TNF) or etoposide. Chromatin immunoprecipitation assays demonstrate that, upon induction, OGT localizes ...

  1. Behavior modification.

    Science.gov (United States)

    Pelham, W E; Fabiano, G A

    2000-07-01

    Attention deficit/hyperactivity disorder (ADHD) is a chronic and substantially impairing disorder. This means that treatment must also be chronic and substantial. Behavior Modification, and in many cases, the combination of behavior modification and stimulant medication, is a valid, useful treatment for reducing the pervasive impairment experienced by children with ADHD. Based on the research evidence reviewed, behavior modification should be the first line of treatment for children with ADHD. PMID:10944662

  2. Amino acids attached to 2'-amino-LNA: Synthesis of DNA mixmer oligonucleotides with increased duplex stability

    DEFF Research Database (Denmark)

    Johannsen, Marie Willaing; Wengel, Jesper; Wamberg, Michael Chr.;

    2010-01-01

    The synthesis of 2'-amino-LNA (locked nucleic acid) opens up exciting possibilities for modification of nucleic acids by conjugation to the 2'-nitrogen. Incorporation of unmodified and N-functionalized 2'-amino-LNA nucleotides improve duplex stability compared to unmodified DNA. 2'-Amino......-LNA nucleosides derivatized with amino acids have been synthesized and incorporated into DNA oligonucleotides. Following oligonucleotide synthesis, peptides have been added using solid phase peptide coupling chem. Modification of oligonucleotides with pos. charged residues greatly improves thermal stability....

  3. Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment.

    Science.gov (United States)

    Hu, Hong; Bai, Xi; Shah, Assar Ali; Dai, Sifa; Wang, Like; Hua, Jinling; Che, Chuanyan; He, Shaojun; Wen, Aiyou; Jiang, Jinpeng

    2016-06-01

    The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased (P consumption (DFC), the concentrations of Gln, glutamate (Glu), and GABA, and the activities of glutaminase and glutamic acid decarboxylase (GAD) in breast muscle at 28, 35, and 42 days, while it increased (P < 0.05) the activities of glutamine synthetase (GS) and gamma-aminobutyric acid transaminase (GABA-T) at 28, 35, and 42 days. Dietary Gln and GABA improved (P < 0.05) DWG and DFC of broilers under cyclic HS during 28-42 days. In breast muscle, the Gln supplementation increased (P < 0.05) the concentrations of Gln (28, 35, and 42 days), Glu (28, 35, and 42 days), and GABA (42 days) and the activities of glutaminase (28, 35, and 42 days) and GAD (28, 35, and 42 days) but decreased (P < 0.05) GS activities at 28, 35, and 42 days and GABA-T activities at 28 days. The addition of GABA increased (P < 0.05) the concentrations of Gln and Glu and activities of glutaminase and GAD, while it decreased (P < 0.05) GABA-T activities at 28, 35, and 42 days. Significant interactions (P < 0.05) between Gln and GABA were found on breast skeletal muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA

  4. What is Nutrition & Metabolism?

    OpenAIRE

    Feinman Richard D; Hussain M Mahmood

    2004-01-01

    Abstract A new Open Access journal, Nutrition & Metabolism (N&M) will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effec...

  5. Selective posttranslational modification of phage-displayed polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, Meng-Lin; Tian, Feng; Schultz, Peter

    2013-11-19

    The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2] cycloaddition reactions and Staudinger modifications.

  6. Effect of intraoperative amino acid infusion on glucose metabolism in dogs%术中静脉输注氨基酸对犬糖代谢的影响

    Institute of Scientific and Technical Information of China (English)

    金琳; 葛圣金; 薛张纲

    2008-01-01

    Objective To investigate the effect of intraoperative amino acid infusion on perioperative glucose metabolism. Methods Thirty-six adult mongrel dogs of both sexes weighing 12-16 kg undergoing partially small intestine resection under general anesthesia were randomly allocated to one of 4 groups (n=9 each): Ⅰ control group received normal saline (C);Ⅱ,Ⅲ,Ⅳ amino acid group (A1, A2, A3) received iv infusion of 2.85%, 5.70% and 11.4% 18-amino acid respectively at 12 ml·kg-1·h-1 during operation starting from skin incision until the end of operation. The animals were premedicated with ketamine and diazepam. Anesthesia was induced with propofol 5-10 mg/kg, fentanyl 2 μg/kg and vecuronium 0.2 mg/kg and maintained with 1%-3% isoflurane and intermittent iv boluses of fentanyl and vecuronium. The animals were intubated and mechanically ventilated. PET CO2 was maintained at 30-40 mm Hg. ECG, MAP, HR, PET CO2 and esophageal T0 were continuously monitored. Venous blood samples were collected before anesthesia (T1), 15 min after induction of anesthesia (T2), 15, 30 min and 1 h after skin incision (T3-5), when abdomen was closed (T6) and 1,2,4,8 and 24 h after operation (T7-11) for determination of plasma glucose, lactate, insulin and glucagon. Liver biopsy was performed at T6-11 and muscle biopsy at T2,6,11 for measurement of hepatic and muscle glucagon. Homa index was used to estimate the degree of insulin resistance. Results The plasma glucose and insulin concentrations were significantly increased at T3-11 as compared with the baseline at T1 in all 4 groups (P<0.05). The plasma insulin concentrations were significantly higher in group A1 (at T6), group A2 (at T3,6) and group A3 (at T3-11) than in group C (P<0.05). Homa index was significantly higher in group A3(at T3-8) than in group C. Conclusion Intraoperative amino acid infusion increases plasma insulin concentration but does not prevent glycogenolysis especially high dose amino acid infusion.%目的 探讨术

  7. 表观遗传修饰在糖尿病代谢记忆中的作用%The role of epigenetic modification in diabetic metabolic memory

    Institute of Scientific and Technical Information of China (English)

    朱汉钢; 陈璐璐; 廖云飞

    2012-01-01

    糖尿病患者在血糖得到控制后,糖尿病并发症仍然持续发展的现象提示了以前暴露于高血糖导致的“代谢记忆”.近来的研究提示“代谢记忆”可能归因于靶细胞的表观遗传改变.许多实验证据显示:组蛋白乙酰基转移酶(HATs)、组蛋白去乙酰化酶(HDACs)、组蛋白甲基转移酶(HMTs)、组蛋白赖氨酸去甲基化酶(KDMs)以及microRNA在调节几种与糖尿病并发症相关的关键基因表观遗传修饰中发挥了重要作用.进一步阐明表观遗传修饰在糖尿病“代谢记忆”中的作用机制以及明确相应的细胞信号通路,对于糖尿病及其并发症的防治有重要意义.%It is evident that metabolic memory,whereby diabetic complications continue to develop and progress in individuals who returned to normal glycemic control after a period of transient hyperglycemia,has long lasting effects.Recent studies suggest that “metabolic memory” may be due to epigenetic changes in target oells.Understanding the molecular changes in chromatin structure and the functional relationship with altered signaling pathways is now considered to represent an important conceptual challenge to explain diabetes and the phenomenon of metabolic memory.Emerging evidences indicate that critical gene-activating epigenetic changes may confer future cell memories. Many experimental evidences show that histone acetyltransferases (HATs), histone deacetylases (HDACs),histone methyltransferases (HMTs),histone lysine demethylases (KDMs),and microRNAs play important roles in the epigenetic changes of several key genes related to diabetic complications. Transient hyperglycemia promotes gene-activating epigenetic changes and signaling events critical in the development and progression of diabetic vascular complications.Further characterisation of these glucose-induced epigenetic events and the identification of key enzymes involved will help us to develop new therapeutic strategies for

  8. Experiment K-6-21. Effect of microgravity on 1) metabolic enzymes of type 1 and type 2 muscle fibers and on 2) metabolic enzymes, neutransmitter amino acids, and neurotransmitter associated enzymes in motor and somatosensory cerebral cortex. Part 1: Metabolic enzymes of individual muscle fibers; part 2: metabolic enzymes of hippocampus and spinal cord

    Science.gov (United States)

    Lowry, O.; Mcdougal, D., Jr.; Nemeth, Patti M.; Maggie, M.-Y. Chi; Pusateri, M.; Carter, J.; Manchester, J.; Norris, Beverly; Krasnov, I.

    1990-01-01

    The individual fibers of any individual muscle vary greatly in enzyme composition, a fact which is obscured when enzyme levels of a whole muscle are measured. The purpose of this study was therefore to assess the changes due to weightless on the enzyme patterns composed by the individual fibers within the flight muscles. In spite of the limitation in numbers of muscles examined, it is apparent that: (1) that the size of individual fibers (i.e., their dry weight) was reduced about a third, (2) that this loss in dry mass was accompanied by changes in the eight enzymes studied, and (3) that these changes were different for the two muscles, and different for the two enzyme groups. In the soleus muscle the absolute amounts of the three enzymes of oxidative metabolism decreased about in proportion to the dry weight loss, so that their concentration in the atrophic fibers was almost unchanged. In contrast, there was little loss among the four enzymes of glycogenolysis - glycolysis so that their concentrations were substantially increased in the atrophic fibers. In the TA muscle, these seven enzymes were affected in just the opposite direction. There appeared to be no absolute loss among the oxidative enzymes, whereas the glycogenolytic enzymes were reduced by nearly half, so that the concentrations of the first metabolic group were increased within the atrophic fibers and the concentrations of the second group were only marginally decreased. The behavior of hexokinase was exceptional in that it did not decrease in absolute terms in either type of muscle and probably increased as much as 50 percent in soleus. Thus, their was a large increase in concentration of this enzyme in the atrophied fibers of both muscles. Another clear-cut finding was the large increase in the range of activities of the glycolytic enzymes among individual fibers of TA muscles. This was due to the emergence of TA fibers with activities for enzymes of this group extending down to levels as low as

  9. 基于柱前衍生-超高效液相色谱-质谱联用技术的植物提取液中氨基化合物代谢谱分析%Metabolic profiling analysis of amino metabolites in plant extract based on pre-column derivatization-ultra high performance liquid chromatography-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    张俊杰; 赵春霞; 赵燕妮; 赵洁妤; 李丽丽; 路鑫; 许国旺

    2015-01-01

    Amino metabolites are important compounds that play a key role in plant growth and development. A metabolic profiling analysis method of amino metabolites in plant extract was developed based on pre-column derivatization-ultra high performance liquid chromatography-mass spectrometry. Using the tobacco leaf as an example,a total of 87 amino metabolites, including amino acids,amines,peptides,alkaloids etc. were detected. The repeatability of the method was good with RSDs of 85 amino metabolites between 1. 5% and 18. 8%. Forty-three amino metabolites validated by standard samples showed good linearity with the correlation coefficients of 0. 993-0. 999,covered linear range of four orders of magnitude. The limits of detection were 0. 03-6. 58 ng/mL. The intra-day and inter-day precisions were 0. 7%-15. 6% and 0. 8%-22. 9%,respectively. The recoveries were 74. 4%-122. 7%. The influence of topping on metabolic profiling of amino metabolites in fresh tobacco was investigated using the developed method. The results showed that the amino metabolites in the upper tobacco leaves were most affected than those in the middle and lower leaves. Metabolism of amino metabolites in the upper leaves after topping was mainly towards the alkaloid synthesis. The method integrated the advantages of triple quadrupole mass spectrometry and high resolution quadrupole-time of flight mass spectrometry. It can be used for metabolic profiling analysis of amino metabolites in plant extract with high sensitivity and selectivity.%氨基化合物在植物生长发育中起着重要作用。本文建立了一种基于柱前衍生-超高效液相色谱-质谱联用技术的植物提取液中氨基化合物代谢谱的分析方法。以烟草鲜叶为例,共检测出87种氨基化合物。其中43种氨基化合物的定量分析结果表明,方法的线性相关系数在0.993~0.999之间,线性范围可达到4个数量级,检出限为0.03~6.58 ng/mL,日内、日间精密度分别为0.7

  10. The Effect of UDP-glucuronosyltransferase 1A1 Expression on the Mutagenicity and Metabolism of the Cooked-Food Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4-5,b]pyridine in CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Malfatti, M A; Wu, R W; Felton, J S

    2004-08-13

    UDP-glucuronosyltransferase proteins (UGT) catalyze the glucuronidation of both endogenous and xenobiotic compounds. In previous studies UGT1A1 has been implicated in the detoxification of certain food-borne-carcinogenic-heterocyclic amines. To determine the importance of UDP-glucuronosyltransferase 1A1 (UGT1A1) in the biotransformation of the cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), genetically modified CHO cells that are nucleotide excision repair-deficient, and express cytochrome P4501A2 (UV5P3 cell line) were transfected with a cDNA plasmid of human UGT1A1 to establish the UDPglucuronosyltransferase 1A1 expressing 5P3hUGT1A1 cell line. Expression of the UGT1A1 gene was verified by screening neogene expressing clonal isolates (G-418 resistant) for their sensitivity to cell killing from PhIP exposure. Five of eleven clones were chosen for further analysis due to their resistance to cell killing. Western blot analysis was used to confirm the presence of the UGT1A1 and CYP1A2 proteins. All five clones displayed a 52 kDa protein band, which corresponded to a UGT1A1 control protein. Only four of the clones had a protein band that corresponded to the CYP1A2 control protein. Correct fragment size of the cDNAs in the remaining 4 clones was confirmed by RT-PCR and quantification of the mRNA product was accomplished by real-time RT-PCR. Expression of UGT1A1 in the transfected cells was 10{sup 4}-10{sup 5} fold higher relative to the UV5P3 parental cells. One clone (No.14) had a 10 fold higher increase in expression at 1.47 x 10{sup 5} over the other three clones. This clone was also the most active in converting N-hydroxy-PhIP to N-hydroxy-PhIP glucuronide conjugates in microsomal metabolism assays. Based on the D{sub 50} values, the cytotoxic effect of PhIP was decreased {approx}350 fold in the 5P3hUGT1A1 cells compared to the UV5P3 control cells. In addition no significant increase in mutation frequency was observed in the

  11. Human Protein and Amino Acid Requirements.

    Science.gov (United States)

    Hoffer, L John

    2016-05-01

    Human protein and amino acid nutrition encompasses a wide, complex, frequently misunderstood, and often contentious area of clinical research and practice. This tutorial explains the basic biochemical and physiologic principles that underlie our current understanding of protein and amino acid nutrition. The following topics are discussed: (1) the identity, measurement, and essentiality of nutritional proteins; (2) the definition and determination of minimum requirements; (3) nutrition adaptation; (4) obligatory nitrogen excretion and the minimum protein requirement; (5) minimum versus optimum protein intakes; (6) metabolic responses to surfeit and deficient protein intakes; (7) body composition and protein requirements; (8) labile protein; (9) N balance; (10) the principles of protein and amino acid turnover, including an analysis of the controversial indicator amino acid oxidation technique; (11) general guidelines for evaluating protein turnover articles; (12) amino acid turnover versus clearance; (13) the protein content of hydrated amino acid solutions; (14) protein requirements in special situations, including protein-catabolic critical illness; (15) amino acid supplements and additives, including monosodium glutamate and glutamine; and (16) a perspective on the future of protein and amino acid nutrition research. In addition to providing practical information, this tutorial aims to demonstrate the importance of rigorous physiologic reasoning, stimulate intellectual curiosity, and encourage fresh ideas in this dynamic area of human nutrition. In general, references are provided only for topics that are not well covered in modern textbooks. PMID:26796095

  12. Adsorption Properties of Amino Acids on Ca/SBA-15 Prepared by Calcium Modification under Microwave Radiation%氨基酸在微波辅助钙改性SBA-15上的吸附性能

    Institute of Scientific and Technical Information of China (English)

    张三山; 张德喜; 肖建国; 刘亚纯; 伏再辉

    2012-01-01

    The calcium modified SBA-15 materials, denoted as Ca / SBA-15 ( MW ) , were prepared by solid-phase method under microwave radiation. The structure of the materials was characterized by small angle XRD, N2 adsorption-desorption, and TEM. Adsorption performance of four typical amino acids on Ca/SBA-15( MW) was studied. Effects of the. calcium loading and pH of amino acid solution on the adsorption performance were investigated. The results show that the calcium modified materials prepared by this method still retain similar structural characteristics of SBA-15, and calcium species are uniformly dispersed in the mesoporous material pore channel. Ca/ SBA-15 (MW) displays better adsorption ability to the adsorption of acidic glutamic acid at pH = 2.0 - 10 as compared to pure silicon SBA-15. Moreover, their adsorption capacity is proportional to calcium content of the samples. For the adsorption of basic amino acid lysine( Lys) , Ca/SBA-15 ( MW) shows the weaker adsorption ability at pH < 10 compared with SBA-15, whereas its adsoiption ability is stronger than that of SBA-15 when the pH value of adsorption solution was adjusted to 10. For the adsorption of some neutral amino acids such as phenylalanine and alanine on SBA-15, their adsorption amount was low at pH =2. 0 ~6. 0 and pH =6. 0 ~ 10. When pH value was ca. 6.0, the maximum adsorption amount of phenylalanine and alanine over SBA-15 was up to 0. 34 and 0. 17 mmol/g, respectively. Ca/SBA-15 ( MW) exhibits a weak adsorption capacity to alanine, and hardly adsorbed phenylalanine. This is likely due to the surface hydrophilicity of the calcium-containing samples, which can lead to a poor adsorption interaction with hydrophobic alanine and especially phenylalanine.%采用微波辐射固相法制备了钙改性SBA-15材料Ca/SBA-15 (MW),借助小角XRD、N2吸附-脱附实验及TEM表征了Ca/SBA-15 (MW)的结构,研究了4种典型的氨基酸在Ca/SBA- 15 (MW)上的吸附性能,并考察了钙负载量和pH值对其

  13. In-frame amber stop codon replacement mutagenesis for the directed evolution of proteins containing non-canonical amino acids: identification of residues open to bio-orthogonal modification.

    Directory of Open Access Journals (Sweden)

    James A J Arpino

    Full Text Available Expanded genetic code approaches are a powerful means to add new and useful chemistry to proteins at defined residues positions. One such use is the introduction of non-biological reactive chemical handles for site-specific biocompatible orthogonal conjugation of proteins. Due to our currently limited information on the impact of non-canonical amino acids (nAAs on the protein structure-function relationship, rational protein engineering is a "hit and miss" approach to selecting suitable sites. Furthermore, dogma suggests surface exposed native residues should be the primary focus for introducing new conjugation chemistry. Here we describe a directed evolution approach to introduce and select for in-frame codon replacement to facilitate engineering proteins with nAAs. To demonstrate the approach, the commonly reprogrammed amber stop codon (TAG was randomly introduced in-frame in two different proteins: the bionanotechnologically important cyt b(562 and therapeutic protein KGF. The target protein is linked at the gene level to sfGFP via a TEV protease site. In absence of a nAA, an in-frame TAG will terminate translation resulting in a non-fluorescent cell phenotype. In the presence of a nAA, TAG will encode for nAA incorporation so instilling a green fluorescence phenotype on E. coli. The presence of endogenously expressed TEV proteases separates in vivo target protein from its fusion to sfGFP if expressed as a soluble fusion product. Using this approach, we incorporated an azide reactive handle and identified residue positions amenable to conjugation with a fluorescence dye via strain-promoted azide-alkyne cycloaddition (SPAAC. Interestingly, best positions for efficient conjugation via SPAAC were residues whose native side chain were buried through analysis of their determined 3D structures and thus may not have been chosen through rational protein engineering. Molecular modeling suggests these buried native residues could become partially

  14. Amino acid analysis in biological fluids by GC-MS

    OpenAIRE

    Kaspar, Hannelore

    2009-01-01

    Amino acids are intermediates in cellular metabolism and their quantitative analysis plays an important role in disease diagnostics. A gas chromatography-mass spectrometry (GC-MS) based method was developed for the quantitative analysis of free amino acids as their propyl chloroformate derivatives in biological fluids. Derivatization with propyl chloroformate could be carried out directly in the biological samples without prior protein precipitation or solid-phase extraction of the amino acid...

  15. Surface Modification for Microreactor Fabrication

    OpenAIRE

    Wladyslaw Torbicz; Jerzy Kruk; Konrad Dudziński; Roberto Canteri; Michele Vendano; Lorenzo Lunelli; Cecilia Pederzolli; Elżbieta Remiszewska; Pijanowska, Dorota G.

    2006-01-01

    In this paper, methods of surface modification of different supports, i.e. glass and polymeric beads for enzyme immobilisation are described. The developed method of enzyme immobilisation is based on Schiff's base formation between the amino groups on the enzyme surface and the aldehyde groups on the chemically modified surface of the supports. The surface of silicon modified by APTS and GOPS with immobilised enzyme was characterised by atomic force microscopy (AFM), time-of-flight secondary ...

  16. D-Amino acid oxidase: new findings.

    Science.gov (United States)

    Pilone, M S

    2000-11-01

    The most recent research on D-amino acid oxidases and D-amino acid metabolism has revealed new, intriguing properties of the flavoenzyme and enlighted novel biotechnological uses of this catalyst. Concerning the in vivo function of the enzyme, new findings on the physiological role of D-amino acid oxidase point to a detoxifying function of the enzyme in metabolizing exogenous D-amino acids in animals. A novel role in modulating the level of D-serine in brain has also been proposed for the enzyme. At the molecular level, site-directed mutagenesis studies on the pig kidney D-amino acid oxidase and, more recently, on the enzyme from the yeast Rhodotorula gracilis indicated that the few conserved residues of the active site do not play a role in acid-base catalysis but rather are involved in substrate interactions. The three-dimensional structure of the enzyme was recently determined from two different sources: at 2.5-3.0 A resolution for DAAO from pig kidney and at 1.2-1.8 A resolution for R. gracilis. The active site can be clearly depicted: the striking absence of essential residues acting in acid-base catalysis and the mode of substrate orientation into the active site, taken together with the results of free-energy correlation studies, clearly support a hydrid transfer type of mechanism in which the orbital steering between the substrate and the isoalloxazine atoms plays a crucial role during catalysis. PMID:11130179

  17. CYP2B6 Non-Coding Variation Associated with Smoking Cessation Is Also Associated with Differences in Allelic Expression, Splicing, and Nicotine Metabolism Independent of Common Amino-Acid Changes

    OpenAIRE

    Bloom, A. Joseph; Martinez, Maribel; Chen, Li-Shiun; Bierut, Laura J; Murphy, Sharon E.; Goate, Alison

    2013-01-01

    The Cytochrome P450 2B6 (CYP2B6) enzyme makes a small contribution to hepatic nicotine metabolism relative to CYP2A6, but CYP2B6 is the primary enzyme responsible for metabolism of the smoking cessation drug bupropion. Using CYP2A6 genotype as a covariate, we find that a non-coding polymorphism in CYP2B6 previously associated with smoking cessation (rs8109525) is also significantly associated with nicotine metabolism. The association is independent of the well-studied non-synonymous variants ...

  18. Bioactivation of the heterocyclic aromatic amine 2-amino-3-methyl-9H-pyrido [2,3-b]indole (MeA alpha C) in recombinant test systems expressing human xenobiotic-metabolizing enzymes

    DEFF Research Database (Denmark)

    Glatt, H.; Pabel, U.; Meinl, W.;

    2004-01-01

    2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and some metabolites were investigated for mutagenicity in mammalian cell lines and bacterial strains engineered for the expression of human enzymes. MeAalphaC induced gene mutations (studied at the hprt locus) in Chinese hamster V79-derived cells...

  19. Amino Acid Prodrugs: An Approach to Improve the Absorption of HIV-1 Protease Inhibitor, Lopinavir

    Directory of Open Access Journals (Sweden)

    Mitesh Patel

    2014-04-01

    Full Text Available Poor systemic concentrations of lopinavir (LPV following oral administration occur due to high cellular efflux by P-glycoprotein (P-gp and multidrug resistance-associated proteins (MRPs and extensive metabolism by CYP3A4 enzymes. In this study, amino acid prodrugs of LPV were designed and investigated for their potential to circumvent efflux processes and first pass effects. Three amino acid prodrugs were synthesized by conjugating isoleucine, tryptophan and methionine to LPV. Prodrug formation was confirmed by the LCMS/MS and NMR technique. Interaction of LPV prodrugs with efflux proteins were carried out in P-gp (MDCK-MDR1 and MRP2 (MDCK-MRP2 transfected cells. Aqueous solubility studies demonstrated that prodrugs generate higher solubility relative to LPV. Prodrugs displayed higher stability under acidic conditions and degraded significantly with rise in pH. Uptake and transport data suggested that prodrugs carry significantly lower affinity towards P-gp and MRP2 relative to LPV. Moreover, prodrugs exhibited higher liver microsomal stability relative to LPV. Hence, amino acid prodrug modification might be a viable approach for enhancing LPV absorption across intestinal epithelial and brain endothelial cells which expresses high levels of P-gp and MRP2.

  20. Anaerobic metabolism of nitroaromatic compounds by sulfate-reducing and methanogenic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Boopathy, R. [Argonne National Lab., IL (United States); Kulpa, C.F. [Notre Dame Univ., IN (United States). Dept. of Biological Sciences

    1994-06-01

    Ecological observations suggest that sulfate-reducing and methanogenic bacteria might metabolize nitroaromatic compounds under anaerobic conditions if appropriate electron donors and electron acceptors are present in the environment, but this ability had not been demonstrated until recently. Most studies on the microbial metabolism of nitroaromatic compounds used aerobic microorganisms. In most cases no mineralization of nitroaromatics occurs, and only superficial modifications of the structures are reported. However, under anaerobic sulfate-reducing conditions, the nitroaromatic compounds reportedly undergo a series of reductions with the formation of amino compounds. For example, trinitrotoluene under sulfate-reducing conditions is reduced to triaminotoluene by the enzyme nitrite reductase, which is commonly found in many Desulfovibrio spp. The removal of ammonia from triaminotoluene is achieved by reductive deamination catalyzed by the enzyme reductive deaminase, with the production of ammonia and toluene. Some sulfate reducers can metabolize toluene to CO{sub 2}. Similar metabolic processes could be applied to other nitroaromatic compounds like nitrobenzene, nitrobenzoic acids, nitrophenols, and aniline. Many methanogenic bacteria can reduce nitroaromatic compounds to amino compounds. In this paper we review the anaerobic metabolic processes of nitroaromatic compounds under sulfate-reducing And methanogenic conditions.

  1. Anaerobic metabolism of nitroaromatic compounds by sulfate-reducing and methanogenic bacteria

    International Nuclear Information System (INIS)

    Ecological observations suggest that sulfate-reducing and methanogenic bacteria might metabolize nitroaromatic compounds under anaerobic conditions if appropriate electron donors and electron acceptors are present in the environment, but this ability had not been demonstrated until recently. Most studies on the microbial metabolism of nitroaromatic compounds used aerobic microorganisms. In most cases no mineralization of nitroaromatics occurs, and only superficial modifications of the structures are reported. However, under anaerobic sulfate-reducing conditions, the nitroaromatic compounds reportedly undergo a series of reductions with the formation of amino compounds. For example, trinitrotoluene under sulfate-reducing conditions is reduced to triaminotoluene by the enzyme nitrite reductase, which is commonly found in many Desulfovibrio spp. The removal of ammonia from triaminotoluene is achieved by reductive deamination catalyzed by the enzyme reductive deaminase, with the production of ammonia and toluene. Some sulfate reducers can metabolize toluene to CO2. Similar metabolic processes could be applied to other nitroaromatic compounds like nitrobenzene, nitrobenzoic acids, nitrophenols, and aniline. Many methanogenic bacteria can reduce nitroaromatic compounds to amino compounds. In this paper we review the anaerobic metabolic processes of nitroaromatic compounds under sulfate-reducing And methanogenic conditions

  2. Nitrosative stress causes amino acid auxotrophy in hmp mutant Salmonella Typhimurium.

    Science.gov (United States)

    Park, Yoon Mee; Park, Hee Jeong; Joung, Young Hee; Bang, Iel Soo

    2011-10-01

    Cytotoxic nitic oxide (NO) damages various bacterial macromolecules, resulting in abnormal metabolism by mechanisms largely unknown. We show that NO can cause amino acid auxotrophy in Salmonella Typhimurium lacking major NO-metabolizing enzyme, flavohemoglobin Hmp. In NO-producing cultures, supplementation with amino acid pool restores growth of Hmp-deficient Salmonella to normal growth phases, whereas excluding Cys or BCAA Leu, Ile, or Val from amino acid pool reduces growth recovery. Data suggest that, without detoxification, NO might inactivate key enzymes in the biosynthesis pathway of amino acids essential for Salmonella replication in amino acid-limiting host environments. PMID:21752086

  3. Metabolic syndrome and migraine

    Directory of Open Access Journals (Sweden)

    Amit eSachdev

    2012-11-01

    Full Text Available Migraine and metabolic syndrome are highly prevaleirnt and costly conditions.The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogensis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise.

  4. Metabolic responses of Saccharomyces cerevisiae to valine and ammonium pulses during four-stage continuous wine fermentations.

    Science.gov (United States)

    Clement, T; Perez, M; Mouret, J R; Sanchez, I; Sablayrolles, J M; Camarasa, C

    2013-04-01

    Nitrogen supplementation, which is widely used in winemaking to improve fermentation kinetics, also affects the products of fermentation, including volatile compounds. However, the mechanisms underlying the metabolic response of yeast to nitrogen additions remain unclear. We studied the consequences for Saccharomyces cerevisiae metabolism of valine and ammonium pulses during the stationary phase of four-stage continuous fermentation (FSCF). This culture technique provides cells at steady state similar to that of the stationary phase of batch wine fermentation. Thus, the FSCF device is an appropriate and reliable tool for individual analysis of the metabolic rerouting associated with nutrient additions, in isolation from the continuous evolution of the environment in batch processes. Nitrogen additions, irrespective of the nitrogen-containing compound added, substantially modified the formation of fermentation metabolites, including glycerol, succinate, isoamyl alcohol, propanol, and ethyl esters. This flux redistribution, fulfilling the requirements for precursors of amino acids, was consistent with increased protein synthesis resulting from increased nitrogen availability. Valine pulses, less efficient than ammonium addition in increasing the fermentation rate, were followed by a massive conversion of this amino acid in isobutanol and isobutyl acetate through the Ehrlich pathway. However, additional routes were involved in valine assimilation when added in stationary phase. Overall, we found that particular metabolic changes may be triggered according to the nature of the amino acid supplied, in addition to the common response. Both these shared and specific modifications should be considered when designing strategies to modulate the production of volatile compounds, a current challenge for winemakers. PMID:23417007

  5. Novel method for chemical modification and patterning of the SU-8 photoresist

    DEFF Research Database (Denmark)

    Blagoi, Gabriela; Keller, Stephan Urs; Boisen, Anja; Jakobsen, Mogens Havsteen

    wetting behaviour of SU-8. The resolution limit of the AQ photopatterning method was 20 μm when using an uncollimated light source. AQ modification followed by a reaction with amino groups of Alexa-647 cadaverine and a Biotin-amino derivative proved possible modification and patterning of polymeric...

  6. DETERMINATION OF REGIMES FOR DIPHTHERIA EXOTOXIN MODIFICATION BY CHEMICAL AND PHYSICOCHEMICAL METHODS

    OpenAIRE

    Antusheva T.I.; Pluhator T.M.; Ryabovol O.V.; Sklyar N.I.,; Ryzhkova T.A.,; Kalinichenko S.V; Babych E.M.; Panova C.V.

    2011-01-01

    The possibility of diphtheria toxoid obtaining using chemical (amino sugars, organic acids) and physicochemical (amino sugars, organic acids, ultrasound, temperature) factors was studied. It was established that modifiers (including formaldehyde) volume content decreasing didn’t have significant influence on diphtheria toxin derived modifications specific activity. It was experimentally determined that diphtheria toxin modifications obtained by the instrumentality of modifier number 1 with or...

  7. Perioperative period: immunological modifications.

    Science.gov (United States)

    Cardinale, F; Chinellato, I; Caimmi, S; Peroni, D G; Franceschini, F; Miraglia Del Giudice, M; Bernardini, R

    2011-01-01

    Surgical stress induces complex modifications in the hemodynamic, metabolic, neuro-hormonal and immune response of the individual. The magnitude of these alterations depends on preoperative events leading to surgery, the severity of surgical trauma, and also on post-operative/post-traumatic complications (multiple hit hypothesis). As in other conditions of tissue damage, surgery trauma is followed by an immune-inflammatory response, initiated at the site of injury by the innate immune system, followed by a compensatory anti-inflammatory (or immunosuppressive) response (CARS), involving mainly cells of the adaptive immune system, which predispose the host to septic complications. The up-regulated inflammatory response, together with a profound impairment of macrophage and cell-mediated immunity, appear to be the cause for patients' increased susceptibility in developing subsequent sepsis after major surgery. PMID:22014920

  8. Evolutionary systems biology of amino acid biosynthetic cost in yeast.

    Directory of Open Access Journals (Sweden)

    Michael D Barton

    Full Text Available Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental

  9. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

    International Nuclear Information System (INIS)

    Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis. The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis

  10. Microbes Promote Amino Acid Harvest to Rescue Undernutrition in Drosophila

    Directory of Open Access Journals (Sweden)

    Ryuichi Yamada

    2015-02-01

    Full Text Available Microbes play an important role in the pathogenesis of nutritional disorders such as protein-specific malnutrition. However, the precise contribution of microbes to host energy balance during undernutrition is unclear. Here, we show that Issatchenkia orientalis, a fungal microbe isolated from field-caught Drosophila melanogaster, promotes amino acid harvest to rescue the lifespan of undernourished flies. Using radioisotope-labeled dietary components (amino acids, nucleotides, and sucrose to quantify nutrient transfer from food to microbe to fly, we demonstrate that I. orientalis extracts amino acids directly from nutrient-poor diets and increases protein flux to the fly. This microbial association restores body mass, protein, glycerol, and ATP levels and phenocopies the metabolic profile of adequately fed flies. Our study uncovers amino acid harvest as a fundamental mechanism linking microbial and host metabolism, and highlights Drosophila as a platform for quantitative studies of host-microbe relationships.

  11. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  12. Epigenetic Modifications and Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Renu A. Kowluru

    2013-01-01

    Full Text Available Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2 and matrix metalloproteinase-9 (MMP-9 are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1, and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

  13. Economic aspects of amino acids production.

    Science.gov (United States)

    Mueller, Udo; Huebner, Susanna

    2003-01-01

    Amino acids represent basic elements of proteins, which as a main source of nutrition themselves serve as a major reserve for maintaining essential functions of humans as well as animals. Taking the recent state of scientific knowledge into account, the industrial sector of amino acids is a priori "suitable" to a specific kind of an ecologically sound way of production, which is based on biotechnology. The following article may point out characteristics of this particular industrial sector and illustrates the applicability of the latest economic methods, founded on development of the discipline of bionics in order to describe economic aspects of amino acids markets. The several biochemical and technological fields of application of amino acids lead to specific market structures in high developed and permanently evolving systems. The Harvard tradition of industrial economics explains how market structures mould the behaviour of the participants and influences market results beyond that. A global increase in intensity of competition confirms the notion that the supply-side is characterised by asymmetric information in contrast to Kantzenbachs concept of "narrow oligopoly" with symmetrical shared knowledge about market information. Departing from this point, certain strategies of companies in this market form shall be derived. The importance of Research and Development increases rapidly and leads to innovative manufacturing methods which replace more polluting manufacturing processes like acid hydrolysis. In addition to these modifications within the production processes the article deals furthermore with the pricing based on product life cycle concept and introduces specific applications of tools like activity based costing and target costing to the field of amino acid production. The authors come to the conclusion that based on a good transferability of latest findings in bionics and ecological compatibility competitors in amino acids manufacturing are well advised

  14. Amino acids in the cultivation of mammalian cells.

    Science.gov (United States)

    Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

    2016-05-01

    Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure. PMID:26832172

  15. Uptake of Branched-Chain Amino Acids by Streptococcus thermophilus

    OpenAIRE

    Akpemado, K. M.; Bracquart, P. A.

    1983-01-01

    The transport of branched-chain amino acids in Streptococcus thermophilus was energy dependent. The metabolic inhibitors of glycolysis and ATPase enzymes were active, but the proton-conducting uncouplers were not. Transport was optimal at temperatures of between 30 and 45°C and at pH 7.0 for the three amino acids leucine, valine, and isoleucine; a second peak existed at pH 5.0 with valine and isoleucine. By competition and kinetics studies, the branched-chain amino acids were found to share a...

  16. Anaerobically functioning mitochondria: evolutionary perspective on modulation of energy metabolism in Mytilus edulis

    Directory of Open Access Journals (Sweden)

    GB Stefano

    2015-01-01

    Full Text Available The mitochondrion represents a compelling biological model of complex organelle development driven by evolutionary modification of permanently enslaved primordial purple non-sulphur bacteria. As an evolutionary modification, the dynamic nature of the mitochondrion has been observed to exhibit biochemical and functional variation, including the capacity for energy production driven by anaerobic respiratory mechanisms. In invertebrates, mitochondrial anaerobic respiration allows the organism to survive at a lower energy state while yielding more ATP than can be achieved by glycolysis alone. Furthermore, a preferred physiological state of lower energy production operationally yields diminished free radical generation, thereby offering a protective existential advantage. It has been established that energy production by the blue mussel, Mytilus edulis, is functionally dependent on anaerobic respiratory mechanisms within the mitochondrion. Importantly, under hypoxic conditions metabolic pathways in M. edulis have been demonstrated to synthesize and utilize amino acid adducts termed opines as chemically defined energy reserves. In addition to the utilization of opines as anaerobic metabolic intermediates by invertebrate organisms, opines were also discovered and characterized as metabolic intermediates in plant parasites, specifically crown gall tumors. A careful review of the biomedical literature indicates mechanistic similarities between anaerobically functioning mitochondria in M. edulis and crown gall tissues and metabolic processes in human tumors. The anaerobically functioning mitochondrion in M. edulis tissues is a potentially valuable high resolution model system for development of novel anticancer therapeutic agents.

  17. Azetidinic amino acids

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Bunch, Lennart; Chopin, Nathalie;

    2005-01-01

    A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form from...... two diastereoisomers that were easily separated and converted in two steps into azetidinic amino acids. Azetidines 35-44 were characterized in binding studies on native ionotropic Glu receptors and in functional assays at cloned metabotropic receptors mGluR1, 2 and 4, representing group I, II and III...

  18. High-level production of C-11-carboxyl-labeled amino acids

    International Nuclear Information System (INIS)

    Carbon-11-labeled amino acids have significant potential as agents for positron tomographic functional imaging. We have developed a rapid, high-temperature, high-pressure modification of the Buecherer--Strecker amino acid synthesis and found it to be quite general for the production of C-11-carboxyl-labeled neutral amino acids. Production of C-11-carboxyl-labeled DL-tryptophan requires certain modifications in the procedure. Twelve different amino acids have been produced to date by this technique. Synthesis and chromatographic purification require approximately 40 min, and C-11-carboxyl-labeled amino acids have been produced in yields of up to 425 mCi. Two C-11-carboxyl-labeled amino acids are being investigated clinically for tumor scanning and two others for pancreatic imaging. Over 120 batches of the various agents have been produced for clinical use over a three-year period

  19. Corynebacterium glutamicum as a Host for Synthesis and Export of d-Amino Acids▿

    OpenAIRE

    Stäbler, Norma; Oikawa, Tadao; Bott, Michael; Eggeling, Lothar

    2011-01-01

    A number of d-amino acids occur in nature, and there is growing interest in their function and metabolism, as well as in their production and use. Here we use the well-established l-amino-acid-producing bacterium Corynebacterium glutamicum to study whether d-amino acid synthesis is possible and whether mechanisms for the export of these amino acids exist. In contrast to Escherichia coli, C. glutamicum tolerates d-amino acids added extracellularly. Expression of argR (encoding the broad-substr...

  20. Readers of histone modifications

    Institute of Scientific and Technical Information of China (English)

    Miyong Yun; Jun Wu; Jerry L Workman; Bing Li

    2011-01-01

    Histone modifications not only play important roles in regulating chromatin structure and nuclear processes but also can be passed to daughter cells as epigenetic marks.Accumulating evidence suggests that the key function of histone modifications is to signal for recruitment or activity of downstream effectors. Here, we discuss the latest discovery of histone-modification readers and how the modification language is interpreted.

  1. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  2. Amino acid analysis.

    Science.gov (United States)

    Crabb, J W; West, K A; Dodson, W S; Hulmes, J D

    2001-05-01

    Amino acid analysis (AAA) is one of the best methods to quantify peptides and proteins. Two general approaches to quantitative AAA exist, namely, classical postcolumn derivatization following ion-exchange chromatography and precolumn derivatization followed by reversed-phase HPLC (RP-HPLC). Excellent instrumentation and several specific methodologies are available for both approaches, and both have advantages and disadvantages. This unit focuses on picomole-level AAA of peptides and proteins using the most popular precolumn-derivatization method, namely, phenylthiocarbamyl amino acid analysis (PTC-AAA). It is directed primarily toward those interested in establishing the technology with a modest budget. PTC derivatization and analysis conditions are described, and support and alternate protocols describe additional techniques necessary or useful for most any AAA method--e.g., sample preparation, hydrolysis, instrument calibration, data interpretation, and analysis of difficult or unusual residues such as cysteine, tryptophan, phosphoamino acids, and hydroxyproline. PMID:18429107

  3. Single amino acid supplementation in aminoacidopathies : a systematic review

    NARCIS (Netherlands)

    van Vliet, Danique; Derks, Terry G. J.; van Rijn, Margreet; de Groot, Martijn J.; MacDonald, Anita; Heiner-Fokkema, M. Rebecca; van Spronsen, Francjan J.

    2014-01-01

    Aminoacidopathies are a group of rare and diverse disorders, caused by the deficiency of an enzyme or transporter involved in amino acid metabolism. For most aminoacidopathies, dietary management is the mainstay of treatment. Such treatment includes severe natural protein restriction, combined with

  4. Updates on industrial production of amino acids using Corynebacterium glutamicum.

    Science.gov (United States)

    Wendisch, Volker F; Jorge, João M P; Pérez-García, Fernando; Sgobba, Elvira

    2016-06-01

    L-Amino acids find various applications in biotechnology. L-Glutamic acid and its salts are used as flavor enhancers. Other L-amino acids are used as food or feed additives, in parenteral nutrition or as building blocks for the chemical and pharmaceutical industries. L-amino acids are synthesized from precursors of central carbon metabolism. Based on the knowledge of the biochemical pathways microbial fermentation processes of food, feed and pharma amino acids have been developed. Production strains of Corynebacterium glutamicum, which has been used safely for more than 50 years in food biotechnology, and Escherichia coli are constantly improved using metabolic engineering approaches. Research towards new processes is ongoing. Fermentative production of L-amino acids in the million-ton-scale has shaped modern biotechnology and its markets continue to grow steadily. This review focusses on recent achievements in strain development for amino acid production including the use of CRISPRi/dCas9, genome-reduced strains, biosensors and synthetic pathways to enable utilization of alternative carbon sources. PMID:27116971

  5. Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor

    Science.gov (United States)

    Krall, Abigail S.; Xu, Shili; Graeber, Thomas G.; Braas, Daniel; Christofk, Heather R.

    2016-01-01

    Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of amino acid uptake is not well-understood. Here we describe a role for asparagine as an amino acid exchange factor: intracellular asparagine exchanges with extracellular amino acids. Through asparagine synthetase knockdown and altering of media asparagine concentrations, we show that intracellular asparagine levels regulate uptake of amino acids, especially serine, arginine and histidine. Through its exchange factor role, asparagine regulates mTORC1 activity and protein synthesis. In addition, we show that asparagine regulation of serine uptake influences serine metabolism and nucleotide synthesis, suggesting that asparagine is involved in coordinating protein and nucleotide synthesis. Finally, we show that maintenance of intracellular asparagine levels is critical for cancer cell growth. Collectively, our results indicate that asparagine is an important regulator of cancer cell amino acid homeostasis, anabolic metabolism and proliferation. PMID:27126896

  6. Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development.

    Science.gov (United States)

    Wendisch, Volker F

    2014-12-01

    Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids. PMID:24922334

  7. Multi-walled carbon nanotubes (MWCNTs) functionalized with amino groups by reacting with supercritical ammonia fluids

    International Nuclear Information System (INIS)

    For the first time, supercritical ammonia fluid was utilized to simply functionalize multi-walled carbon nanotube (MWCNT) with amino groups. The successful amino functionalization of MWCNTs was proven and the physicochemical properties of MWCNTs before and after supercritical ammonia fluids modifications were characterized using X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), atomic force microscope (AFM) and Raman spectroscopy. The results also indicated that the supercritical ammonia fluids had the visible effects on the nanostructure of carbon nanotubes. Our novel modification approach provides an easy way to modify MWCNTs with amino groups, which is very useful for realizing 'carbon nanotube economy' in the near future.

  8. Phenotypic characterization of Corynebacterium glutamicum using elementary modes towards synthesis of amino acids

    OpenAIRE

    Radhakrishnan, Devesh; Rajvanshi, Meghna; Venkatesh, K. V.

    2010-01-01

    Elementary flux mode (EFM) analysis is a powerful tool to represent the metabolic network structure and can be further utilized for flux analysis. The method enables characterization and quantification of feasible phenotypes in microbes. EFM analysis was employed to characterize the phenotype of Corynebacterium glutamicum to yield various amino acids. The metabolic network of C. glutamicum yielded 62 elementary modes by incorporating the accumulation of amino acids namely, lysine, alanine, va...

  9. The Biosynthetic Pathways for Shikimate and Aromatic Amino Acids in Arabidopsis thaliana

    OpenAIRE

    Tzin, Vered; Galili, Gad

    2010-01-01

    The aromatic amino acids phenylalanine, tyrosine and tryptophan in plants are not only essential components of protein synthesis, but also serve as precursors for a wide range of secondary metabolites that are important for plant growth as well as for human nutrition and health. The aromatic amino acids are synthesized via the shikimate pathway followed by the branched aromatic amino acid metabolic pathway, with chorismate serving as a major branch point intermediate metabolite. Yet, the regu...

  10. [Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015].

    Science.gov (United States)

    Davydova, A I; Klodt, P M; Kudrin, V S; Kuznetsova, E A; Narkevich, V B

    2010-03-01

    Results of a neurochemical study of the effects of the new anxiolytic drugs afobazole and ladasten on the synthesis and metabolism of monoamines and their metabolites determined by HPLC on the model of monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) in the brain structures of Wistar rats are reported. A decrease in the levels of DOPAC in hypothalamus and HVA in striatum after afobazole injection may be evidence of an inhibitory action of this drug on the activity of monoamine oxidase (MAO-A), which is the main enzyme involved in dopamine biodegradation. Afobazole was also found to increase the content of serotonin (5-HT) as well as its precursor (5-OTP) and its main metabolite (5-HIAA) in hypothalamus by up to 50, 60 and 50%, respectively, which confirms a hypothesis that this anxiolytic drug can modulate the activity of tryptophan hydroxylase (5-OTP synthesis enzyme). In contrast to afobazole, ladasten demonstrated the ability to increase the level of L-DOPA (a dopamine precursor) in virtually all functional structures of the brain (except for hippocamp), which may support the hypothesis suggestion concerning a predominant action of this drug on the activity of tyrosine hydroxylase. Ladasten exhibited selectivity with respect to the dopaminergic system and affected only parameters of the dopamine metabolism, in particular, by increasing the HVA content in nucleus accumbens and decreasing it in the hypothalamus. The drug also affected the dopamine turnover parameters, producing an increase in both HVA/dopamine ratio in nucleus accumbens and DOPAC/dopamine ratio in hippocamp. PMID:20408420

  11. Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production

    Directory of Open Access Journals (Sweden)

    Yoon Byoung

    2009-01-01

    Full Text Available Abstract Background Deletion of large blocks of nonessential genes that are not needed for metabolic pathways of interest can reduce the production of unwanted by-products, increase genome stability, and streamline metabolism without physiological compromise. Researchers have recently constructed a reduced-genome Escherichia coli strain MDS42 that lacks 14.3% of its chromosome. Results Here we describe the reengineering of the MDS42 genome to increase the production of the essential amino acid L-threonine. To this end, we over-expressed a feedback-resistant threonine operon (thrA*BC, deleted the genes that encode threonine dehydrogenase (tdh and threonine transporters (tdcC and sstT, and introduced a mutant threonine exporter (rhtA23 in MDS42. The resulting strain, MDS-205, shows an ~83% increase in L-threonine production when cells are grown by flask fermentation, compared to a wild-type E. coli strain MG1655 engineered with the same threonine-specific modifications described above. And transcriptional analysis revealed the effect of the deletion of non-essential genes on the central metabolism and threonine pathways in MDS-205. Conclusion This result demonstrates that the elimination of genes unnecessary for cell growth can increase the productivity of an industrial strain, most likely by reducing the metabolic burden and improving the metabolic efficiency of cells.

  12. INTERRUPTION OF AMINO ACIDS MOLECULAR ASYMMETRY (D/L- ENANTIOMERS DURING NORMAL AGING AND NEURODEGENERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    A.V. Chervyakov

    2010-05-01

    Full Text Available Some facts about D-amino acids, their diffusion in human’s and animal’s organisms, metabolism, identification methods, involving in ageing and pathogenesis of some neurodegenerative diseases are show in this review. Also there is discussing the role of amino acid molecular asymmetry (D and L enantiomers ratio as a fundamental asymmetry of living matter.

  13. EFFECT OF TETRACYCLINES ON THE INTRACELLULAR AMINO ACIDS OF MOLDS.

    Science.gov (United States)

    FREEMAN, B A; CIRCO, R

    1963-07-01

    Freeman, Bob A. (University of Chicago, Chicago, Ill.) and Richard Circo. Effect of tetracyclines on the intracellular amino acids of molds. J. Bacteriol. 86:38-44. 1963.-The tetracycline antibiotics were shown to alter the amino acid metabolism of molds whose growth is not markedly affected. Eight molds were grown in the presence of these antiobiotics; four exhibited a general reduction in the concentration of the intracellular amino acids, except for glutamic acid and alanine. In most of these four cultures, the tetracyclines also caused the complete disappearance of arginine, lysine, proline, phenylalanine, and tyrosine from the intracellular amino acid pool. The significance of these observations and the usefulness of the method in the study of the mechanisms of antibiotic action are discussed. PMID:14051820

  14. Evaluation on the Apparent Metabolic Energy and Apparent Heal Amino Acid Digestibility of Broccoli LPC and Broccoli Residues for Broilers%西兰花叶蛋白和茎叶粉对肉仔鸡代谢能和回肠氨基酸表观消化率的影响

    Institute of Scientific and Technical Information of China (English)

    杨桂芹; 梁丽萍; 李建涛; 刘国华; 张姝; 郑爱娟

    2011-01-01

    通过2个试验测定了西兰花叶蛋白和茎叶粉在肉仔鸡中的氮校正表观代谢能和回肠氨基酸的表观消化率,为合理利用西兰花资源提供科学依据和数据参考.试验1选用体重相近的22日龄健康肉仔鸡144只,随机分成3个组,每组8个重复,公母各50%.其中1组饲喂基础日粮,另2组分别饲喂试验日粮(西兰花叶蛋白30%替代基础日粮,西兰花茎叶粉35%替代基础日粮).选用TiO2为外源指示剂进行代谢试验;试验2选用体重相近的26日龄健康肉仔鸡96只,随机分为2组,每组8个重复,公母各50%.选用TiO2为外源指示剂,采用回肠末端法进行代谢试验.结果表明:西兰花叶蛋白和茎叶粉在肉仔鸡中的表观代谢能分别为8.86MJ·kg-1和2.48 MJ·kg-1,氮校正表观代谢能分别为8.14 MJ·kg-1和1.86 MJ·kg-1;西兰花叶蛋白和茎叶粉在肉仔鸡中4种限制性氨基酸的回肠末端表观消化率分别为赖氨酸(48.11±4.28)%和(73.00±6.64)%,蛋氨酸(39.51±4.60)%和(79.18±3.91)%,苏氨酸(33.11±4.66)%和(59.38±6.25)%,胱氨酸(33.47±2.94)%和(65.82±4.46)%;存肉仔鸡中17种氨基酸的回肠末端表观消化率的平均值为(39.57±4.45)%和(71.75±4.85)%.可见,西兰花茎叶粉在肉仔鸡中的表观代谢能较低,西兰花叶蛋白在肉仔鸡中回肠末端氨基酸的消化率较低.%To assess the apparent metabolic energy and apparent ileal amino acid digestibility of broccoli leaf protein concentrate (LPC) and broccoli residues for broilers, two experiments were carried out. In experiment one,one hundred and forty-four 22-day-old broilers were allocated randomly into three treatments,each of them contained eight repetitions, male and female half and haft. Titanium dioxide was used as the exogenous indicator to carry out the metabolic test, One group was fed basic diet, other two groups were fed test diets in which the basic diet was replaced by 30% broccoli LPC and 35% broccoli residues respectively. In

  15. Mechanisms controlling renal hemodynamics and electrolyte excretion during amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Woods, L.L.; Mizelle, H.L.; Montani, J.P.; Hall, J.E.

    1986-08-01

    Our purpose was to investigate the mechanisms by which increased plasma amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR). Since transport of amino acids and Na is linked in the proximal tubule, the authors hypothesized that increased amino acids might stimulate proximal tubular Na reabsorption (PR/sub Na/) and thus increase RBF and GFR by a macula densa feedback mechanism. A solution of four amino acids (Ala, Ser, Gly, Pro) was infused intravenously into anesthetized dogs with normal kidneys (NK) and with kidneys in which the tubuloglomerular feedback mechanism was blunted by lowering renal artery pressure (LPK) or blocked by making the kidneys nonfiltering (NFK). In NK, RBF and GFR increased by 35 +/- 4% and 30 +/- 7% after 90 min of amino acid infusion, while PR/sub Na/ (estimated from lithium clearance) and O2 consumption increased by 31 +/- 5% and 29 +/- 5% and distal Na delivery remained relatively constant. Autoregulation of RBF and GFR in response to step deceases in renal artery pressure was impaired during amino acids in NK. The hemodynamic responses to amino acids were abolished in LPK and NFK. Infusion of the nonmetabolized -aminoisobutyric acid into NK produced changes in renal hemodynamics that were similar to the responses observed with the four metabolizable amino acids. These data are consistent with the hypothesis that elevation of plasma amino acids increases RBF and GFR by a mechanism that requires an intact macula densa feedback. Metabolism of the amino acids does not appear to be necessary for these changes to occur.

  16. Amino alky tetrazoles

    International Nuclear Information System (INIS)

    Stable 5-(aminoalkyl)tetrazole complexes are synthesized with heavy metal ions in water solutions (with Cu2+; Ni2+, Co2+, Zn2+, Cd2+, Ca2+, Mg2+ ions). Complexing study has been carried out by potentiometry titration and spectrophotometric methods. The composition of the obtained complexes is 1:2 (metal-ligand). pH Regions of the complex existence are given (for Cd2+ - 5.8-9.0; 6.0-9.5). The stability constants of complexes with metals have been calculated. Optimal structure for complexing is the existence of ethylene bridge between the amino group and tetrazole ring

  17. Surface Modification for Microreactor Fabrication

    Directory of Open Access Journals (Sweden)

    Wladyslaw Torbicz

    2006-04-01

    Full Text Available In this paper, methods of surface modification of different supports, i.e. glass andpolymeric beads for enzyme immobilisation are described. The developed method ofenzyme immobilisation is based on Schiff’s base formation between the amino groups onthe enzyme surface and the aldehyde groups on the chemically modified surface of thesupports. The surface of silicon modified by APTS and GOPS with immobilised enzymewas characterised by atomic force microscopy (AFM, time-of-flight secondary ion massspectroscopy (ToF-SIMS and infrared spectroscopy (FTIR. The supports withimmobilised enzyme (urease were also tested in combination with microreactors fabricatedin silicon and Perspex, operating in a flow-through system. For microreactors filled withurease immobilised on glass beads (Sigma and on polymeric beads (PAN, a very high andstable signal (pH change was obtained. The developed method of urease immobilisationcan be stated to be very effective.

  18. Behavior Modification is not...

    Science.gov (United States)

    Tawney, James W.; And Others

    1973-01-01

    Identified are misconceptions of behavior modification procedures according to which behavior modification is connected mistakenly with noncontingent reinforcement, partial change of a teacher's behavior, decelerations of inappropriate behaviors only, dependency producing technology, teacher dominated activity, a single type of classroom…

  19. Diastereoselective Ugi reaction for the synthesis of unnatural amino esters

    Directory of Open Access Journals (Sweden)

    Rafael Oliveira Rocha

    2012-06-01

    Full Text Available Multicomponent Reactions (MCR are useful reactions to obtain complex products by the simple mixture of 3 or more reactants. The classic Ugi reaction (4-UCR involves a mixture of an amine, aldehyde, isocyanide and a carboxylic acid, giving peptoides as products. Some modifications of this reaction have been reported, among which the use of amino acids and Lewis acids, such as titanium (IV chloride, to induce stereoselectivity in good ratio. In this work we demonstrate the efficiency of different Lewis acids in the modified Ugi reaction and good levels of diastereoselectivity and yields in the synthesis of unnatural secondary amino esters.

  20. Roles of phytochemicals in amino acid nutrition.

    Science.gov (United States)

    Kong, Xiangfeng; Wu, Guoyao; Yin, Yinlong

    2011-01-01

    Chinese herbal medicine (CHM) is often used as dietary supplements to maintain good health in animals and humans. Here, we review the current knowledge about effects of CHM (including ultra-fine Chinese herbal powder, Acanthopanax senticosus extracts, Astragalus polysaccharide, and glycyrrhetinic acid) as dietary additives on physiological and biochemical parameters in pigs, chickens and rodents. Additionally, we propose possible mechanisms for the beneficial effects of CHM on the animals. These mechanisms include (a) increased digestion and absorption of dietary amino acids; (b) altered catabolism of amino acids in the small intestine and other tissues; (c) enhanced synthesis of functional amino acids (e.g., arginine, glutamine and proline) and polyamines; and (d) improved metabolic control of nutrient utilization through cell signaling. Notably, some phytochemicals and glucocorticoids share similarities in structure and physiological actions. New research findings provide a scientific and clinical basis for the use of CHM to improve well-being in livestock species and poultry, while enhancing the efficiency of protein accretion. Results obtained from animal studies also have important implications for human nutrition and health. PMID:21196382

  1. Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications

    Directory of Open Access Journals (Sweden)

    Asadollahi Mohammad A

    2010-12-01

    Full Text Available Abstract Background The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where selective pressure is applied to a partially genetically engineered strain to confer a desirable phenotype. The exact genetic modification or resulting genotype that leads to the improved phenotype is often not identified or understood to enable further metabolic engineering. Results In this work we performed whole genome high-throughput sequencing and annotation can be used to identify single nucleotide polymorphisms (SNPs between Saccharomyces cerevisiae strains S288c and CEN.PK113-7D. The yeast strain S288c was the first eukaryote sequenced, serving as the reference genome for the Saccharomyces Genome Database, while CEN.PK113-7D is a preferred laboratory strain for industrial biotechnology research. A total of 13,787 high-quality SNPs were detected between both strains (reference strain: S288c. Considering only metabolic genes (782 of 5,596 annotated genes, a total of 219 metabolism specific SNPs are distributed across 158 metabolic genes, with 85 of the SNPs being nonsynonymous (e.g., encoding amino acid modifications. Amongst metabolic SNPs detected, there was pathway enrichment in the galactose uptake pathway (GAL1, GAL10 and ergosterol biosynthetic pathway (ERG8, ERG9. Physiological characterization confirmed a strong deficiency in galactose uptake and metabolism in S288c compared to CEN.PK113-7D, and similarly, ergosterol content in CEN.PK113-7D was significantly higher in both glucose and galactose supplemented cultivations compared to S288c. Furthermore, DNA microarray profiling of S288c and CEN.PK113-7D in both glucose and galactose batch cultures did not provide a clear hypothesis for major phenotypes observed, suggesting that

  2. Modify or die? - RNA modification defects in metazoans

    Science.gov (United States)

    Sarin, L Peter; Leidel, Sebastian A

    2014-01-01

    Chemical RNA modifications are present in all kingdoms of life and many of these post-transcriptional modifications are conserved throughout evolution. However, most of the research has been performed on single cell organisms, whereas little is known about how RNA modifications contribute to the development of metazoans. In recent years, the identification of RNA modification genes in genome wide association studies (GWAS) has sparked new interest in previously neglected genes. In this review, we summarize recent findings that connect RNA modification defects and phenotypes in higher eukaryotes. Furthermore, we discuss the implications of aberrant tRNA modification in various human diseases including metabolic defects, mitochondrial dysfunctions, neurological disorders, and cancer. As the molecular mechanisms of these diseases are being elucidated, we will gain first insights into the functions of RNA modifications in higher eukaryotes and finally understand their roles during development. PMID:25692999

  3. Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1.

    Science.gov (United States)

    Nässl, Anna-Maria; Rubio-Aliaga, Isabel; Fenselau, Henning; Marth, Mena Katharina; Kottra, Gabor; Daniel, Hannelore

    2011-07-01

    The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1(-/-) compared with Pept1(+/+) animals, suggesting that amino acid handling is altered. Plasma appearance rates of (15)N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism. PMID:21350187

  4. Selective modification of phosphoribulokinase cysteines

    Energy Technology Data Exchange (ETDEWEB)

    Krieger, T.J.; Mende-Mueller, L.M.; Miziorko, H.M.

    1987-05-01

    The most reactive sulfhydryl in native phosphoribulokinase can be selectively alkylated with iodoacetate; complete loss of activity results. Composition and N-terminal analyses of the peptide bearing this -SH show that cys-16 is the modification site. In the presence of Mg and ATP, a nonessential -SH is modified; catalytic activity is unchanged. The peptide bearing this cysteine has been characterized by amino acid composition and N-terminal analyses (Phe-Phe-Asn-Pro-Val-Tyr-(Ile/Leu)...). Enzyme alkylated at this site is subject to reversible oxidative inactivation, showing that this cysteine is not involved in regulation of activity. A cysteine distinct from this nonessential residue is suggested by crosslinking studies to be close (5a) to cys-16. The site-directed inhibitor fluorosulfonylbenzoyladenosine (FSBA) inactivates enzyme by modifying cys-16. Carboxymethylation of enzyme after FSBA incorporation, followed by DTT treatment, unmasks the initial modification site and allows (/sup 14/C)-iodoacetate labeling. The tryptic peptide bearing this residue co-chromatographs with and is identical in composition to the cys-16 containing peptide.

  5. Covalently functionalized graphene sheets with biocompatible natural amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Mallakpour, Shadpour, E-mail: mallak@cc.iut.ac.ir [Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Abdolmaleki, Amir, E-mail: abdolmaleki@cc.iut.ac.ir [Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Borandeh, Sedigheh [Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of)

    2014-07-01

    Graphene sheets were covalently functionalized with aromatic–aliphatic amino acids (phenylalanine and tyrosine) and aliphatic amino acids (alanine, isoleucine, leucine, methionine and valine) by simple and green procedure. For this aim, at first natural graphite was converted into graphene oxide (GO) through strong oxidation procedure; then, based on the surface-exposed epoxy and carboxylic acid groups in GO solid, its surface modification with naturally occurring amino acids, occurred easily throughout the corresponding nucleophilic substitution and condensation reactions. Amino acid functionalized graphene demonstrates stable dispersion in water and common organic solvents. Fourier transform infrared, Raman and X-ray photoelectron spectroscopies, X-ray diffraction, field emission scanning electron microscopy and transmission electron microscopy were used to investigate the nanostructures and properties of prepared materials. Each amino acid has different considerable effects on the structure and morphology of the pure graphite, from increasing the layer spacing to layer scrolling, based on their structures, functional groups and chain length. In addition, therogravimetric analysis was used for demonstrating a successful grafting of amino acid molecules to the surface of graphene.

  6. Microbial Products Trigger Amino Acid Exudation from Plant Roots1

    Science.gov (United States)

    Phillips, Donald A.; Fox, Tama C.; King, Maria D.; Bhuvaneswari, T.V.; Teuber, Larry R.

    2004-01-01

    Plants naturally cycle amino acids across root cell plasma membranes, and any net efflux is termed exudation. The dominant ecological view is that microorganisms and roots passively compete for amino acids in the soil solution, yet the innate capacity of roots to recover amino acids present in ecologically relevant concentrations is unknown. We find that, in the absence of culturable microorganisms, the influx rates of 16 amino acids (each supplied at 2.5 μm) exceed efflux rates by 5% to 545% in roots of alfalfa (Medicago sativa), Medicago truncatula, maize (Zea mays), and wheat (Triticum aestivum). Several microbial products, which are produced by common soil microorganisms such as Pseudomonas bacteria and Fusarium fungi, significantly enhanced the net efflux (i.e. exudation) of amino acids from roots of these four plant species. In alfalfa, treating roots with 200 μm phenazine, 2,4-diacetylphloroglucinol, or zearalenone increased total net efflux of 16 amino acids 200% to 2,600% in 3 h. Data from 15N tests suggest that 2,4-diacetylphloroglucinol blocks amino acid uptake, whereas zearalenone enhances efflux. Thus, amino acid exudation under normal conditions is a phenomenon that probably reflects both active manipulation and passive uptake by microorganisms, as well as diffusion and adsorption to soil, all of which help overcome the innate capacity of plant roots to reabsorb amino acids. The importance of identifying potential enhancers of root exudation lies in understanding that such compounds may represent regulatory linkages between the larger soil food web and the internal carbon metabolism of the plant. PMID:15347793

  7. Radiation-induced increase in the release of amino acids by isolated, perfused skeletal muscle

    International Nuclear Information System (INIS)

    Local exposure of the hindquarter of the rat to 15Gy of gamma-radiation resulted, 4-6h after irradiation, in increased release of amino acids by the isolated, perfused hindquarter preparation, 70% of which is skeletal muscle. This increase in release involves not only alanine and glutamine, but also those amino acids not metabolized by muscle and, therefore, released in proportion to their occurrence in muscle proteins. Because metabolic parameters and content of energy-rich phosphate compounds in muscle remain unchanged, it is unlikely that general cellular damage is the underlying cause of the radiation-induced increase in amino acid release. The findings strongly favour the hypothesis that increased availability of amino acids results from enhanced protein break-down in skeletal muscle which has its onset shortly after irradiation. This radiation-induced disturbance in protein metabolism might be one of the pathogenetic factors in the aetiology of radiation myopathy. (author)

  8. Transport of aromatic amino acids by Brevibacterium linens.

    OpenAIRE

    Boyaval, P; Moreira, E; Desmazeaud, M. J.

    1983-01-01

    Whole metabolizing Brevibacterium linens cells were used to study the transport of aromatic amino acids. Kinetic results followed the Michaelis-Menten equation with apparent Km values for phenylalanine, tyrosine, and tryptophan of 24, 3.5, and 1.8 microM. Transport of these amino acids was optimum at pH 7.5 and 25 degrees C for phenylalanine and pH 8.0 and 35 degrees C for tyrosine and tryptophan. Crossed inhibitions were all noncompetitive. The only marked stereospecificity was for the L for...

  9. Metabolic Disorders

    Science.gov (United States)

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  10. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  11. Amino Acid Carbamates As Prodrugs Of Resveratrol.

    Science.gov (United States)

    Mattarei, Andrea; Azzolini, Michele; La Spina, Martina; Zoratti, Mario; Paradisi, Cristina; Biasutto, Lucia

    2015-01-01

    Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted carbamate ester (-OC(O)NHR) linkage with a natural amino acid (Leu, Ile, Phe, Thr) to prevent conjugation and modulate the physicochemical properties of the molecule. We also report a convenient, high-yield protocol to obtain derivatives of this type. The new carbamate ester derivatives are stable at pH 1, while they undergo slow hydrolysis at physiological pH and hydrolyse with kinetics suitable for use in prodrugs in whole blood. After administration to rats by oral gavage the isoleucine-containing prodrug was significantly absorbed, and was present in the bloodstream as non-metabolized unaltered or partially deprotected species, demonstrating effective shielding from first-pass metabolism. We conclude that prodrugs based on the N-monosubstituted carbamate ester bond have the appropriate stability profile for the systemic delivery of phenolic compounds. PMID:26463125

  12. Genetics of metabolic resistance.

    Science.gov (United States)

    Richter, Otto; Langemann, Dirk; Beffa, Roland

    2016-09-01

    Herbicide resistance has become a major issue for many weeds. Metabolic resistance refers to the biochemical processes within organisms that degrade herbicides to less toxic compounds, resulting in a shift of the dose response curve. This type of resistance involves polygenic inheritance. A model is presented linking the biochemical pathway of amino acid synthesis and the detoxifying pathway of an inhibitor of the key enzyme ALS. From this model, resistance factors for each biotype are derived, which are then applied to a polygenic population genetic model for an annual weed plant. Polygenic inheritance is described by a new approach based on tensor products of heredity matrices. Important results from the model are that low dose regimes favour fast emergence of resistant biotypes and that the emergence of resistant biotypes occurs as abrupt outbreaks. The model is used to evaluate strategies for the management of metabolic resistance. PMID:27424952

  13. tRNAs: cellular barcodes for amino acids

    DEFF Research Database (Denmark)

    Banerjee, Rajat; Chen, Shawn; Dare, Kiley;

    2010-01-01

    The role of tRNA in translating the genetic code has received considerable attention over the last 50 years, and we now know in great detail how particular amino acids are specifically selected and brought to the ribosome in response to the corresponding mRNA codon. Over the same period, it has...... also become increasingly clear that the ribosome is not the only destination to which tRNAs deliver amino acids, with processes ranging from lipid modification to antibiotic biosynthesis all using aminoacyl-tRNAs as substrates. Here we review examples of alternative functions for tRNA beyond...... translation, which together suggest that the role of tRNA is to deliver amino acids for a variety of processes that includes, but is not limited to, protein synthesis....

  14. 补充支链氨基酸对失眠老年大鼠行为和糖代谢的影响%Effects of branched-chain amino acids supplementation on behaviour and glucose metabolism in aged rats subjected to in- somnia(

    Institute of Scientific and Technical Information of China (English)

    欧阳儒颖; 张济生; 蔡懿灵

    2014-01-01

    Objectives To explore the effects of branched-chain amino acids( BCAA) supplementation on behaviour and glucose metabolism in aged rats subjected to isomnia.Methods Experimental model of isomnia was established by use of sleep deprivation method(flower pot),thirty aged male rats were divided into five groups randomly:C(control)group, 6h(6 hours sleep per day) group, 6hB(6 hours sleep per day and fed fodder enriched with BCAA)group,4h(4 hours sleep per day)group and 4hB group.Re-sults Time of resting on the center lattic,number of make-up and number of excrete were significantly increased in experimental groups compared with C group(PC group>4h group(P0.05).Conpared with C group,the level of FPG in experimential groups were increased apparently (P4h (P<0.05).Conclusions supplementation of BCAA may ameliorates behavior and glucose metabolism in aged rats subjected to isomnia.%目的:探讨补充支链氨基酸( branched-chain amino acids,BCAA)对失眠老年大鼠行为和糖代谢的影响。方法采用小平台水环境的睡眠剥夺方法建立动物失眠模型,30只雄性老年大鼠随机分为对照组( C组)、6h组(每天6小时睡眠组)、6hB组(每天睡眠6小时,进食添加BCAA的饲料),4h组(每天睡眠4小时),4hB组(每天睡眠4小时,进食添加BCAA的饲料)。结果实验组大鼠的修饰行为次数、中央格停留时间、粪便颗粒数均高于C组,差异具有显著性( P<0.05)。且修饰行为次数、中央格停留时间4hB组<4h组(P<0.05);旷场实验得分6h组>C组>4h组,差异具有显著性(P<0.05)。但旷场实验得分、粪便颗粒数6h组与6hB组,4h组与4hB组比较无差异(P>0.05)。与C组比较,实验组的FPG水平显著升高(P<0.05);但4hB组<4h组(P<0.05)。与C组比较4h组和4hB组的血清INS水平显著升高(P<0.05),且4hB组<4h组(P<0.05)。与C组比较,

  15. Did Evolution Select a Nonrandom "Alphabet" of Amino Acids?

    Science.gov (United States)

    Philip, Gayle K.; Freeland, Stephen J.

    2011-04-01

    The last universal common ancestor of contemporary biology (LUCA) used a precise set of 20 amino acids as a standard alphabet with which to build genetically encoded protein polymers. Considerable evidence indicates that some of these amino acids were present through nonbiological syntheses prior to the origin of life, while the rest evolved as inventions of early metabolism. However, the same evidence indicates that many alternatives were also available, which highlights the question: what factors led biological evolution on our planet to define its standard alphabet? One possibility is that natural selection favored a set of amino acids that exhibits clear, nonrandom properties - a set of especially useful building blocks. However, previous analysis that tested whether the standard alphabet comprises amino acids with unusually high variance in size, charge, and hydrophobicity (properties that govern what protein structures and functions can be constructed) failed to clearly distinguish evolution's choice from a sample of randomly chosen alternatives. Here, we demonstrate unambiguous support for a refined hypothesis: that an optimal set of amino acids would spread evenly across a broad range of values for each fundamental property. Specifically, we show that the standard set of 20 amino acids represents the possible spectra of size, charge, and hydrophobicity more broadly and more evenly than can be explained by chance alone.

  16. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    Science.gov (United States)

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  17. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    Science.gov (United States)

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  18. Oxidative Modification of Cytochrome c by Tetrahydropapaveroline, an Isoquinoline-Derived Neurotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jung Hoon [Cheongju Univ., Cheongju (Korea, Republic of)

    2013-02-15

    Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

  19. The seasonal fluctuation of plasma amino acids in aquarium-maintained bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Miyaji, Kazuki; Ohta, Mitsuaki; Nagao, Kenji; Ohtani, Nobuyo; Bannai, Makoto

    2012-07-01

    Although there has been extensive research on plasma amino acid profiles of mammals, there is currently a lack of information on seasonal differences in the concentrations of plasma amino acids specifically in cetaceans. The present study examined the response of the plasma amino acids to seasonal changes in the culture environment after controlling for the effect of sex and age. Significant seasonal changes in plasma carnosine (P=0.012), cystine (P=0.0014), isoleucine (P=0.0042), methionine (P=0.002), ornithine (P=0.0096), and taurine (P=0.032) were observed. These amino acids were mainly related to capacity for exercise, ammonia detoxification, thermoregulation, and osmoregulation. We proposed that optimizing plasma amino acids levels by supplementation of amino acids should be of considerable benefit for aquarium-maintained bottlenose dolphins. This study constitutes a first step towards improving our understanding of the metabolism of aquarium-maintained bottlenose dolphins. We also revealed that the ratio of tryptophan to large neutral amino acids significantly declined (P=0.0076), suggesting reduction in serotonin synthesis in winter and autumn. Although further studies are needed, this finding implied that bottlenose dolphins could produce behavioral changes seasonally by the alteration of serotonin activity. To better understand the metabolic machinery for amino acids that facilitate the adaptation of marine mammals to their environments, it is essential to continue monitoring of and further investigations into relationships between plasma amino acids and specific environmental factors. PMID:22333514

  20. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B;

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation...

  1. Microfluidics in amino acid analysis.

    Science.gov (United States)

    Pumera, Martin

    2007-07-01

    Microfluidic devices have been widely used to derivatize, separate, and detect amino acids employing many different strategies. Virtually zero-dead volume interconnections and fast mass transfer in small volume microchannels enable dramatic increases in on-chip derivatization reaction speed, while only minute amounts of sample and reagent are needed. Due to short channel path, fast subsecond separations can be carried out. With sophisticated miniaturized detectors, the whole analytical process can be integrated on one platform. This article reviews developments of lab-on-chip technology in amino acid analysis, it shows important design features such as sample preconcentration, precolumn and postcolumn amino acid derivatization, and unlabeled and labeled amino acid detection with focus on advanced designs. The review also describes important biomedical and space exploration applications of amino acid analysis on microfluidic devices. PMID:17542043

  2. The effect of dispensable amino acids on nitrogen and amino acid losses in Atlantic salmon (Salmo salar) fry fed a protein-free diet

    OpenAIRE

    Abboudi, T.; Mambrini, M.; Larondelle, Y.; Rollin, X.

    2009-01-01

    The nutritional role of dispensable amino acids (DAAs) has been seldom studied in fish, while the metabolism of these species is orientated toward the oxidation of amino acids (AAs) for energetic purpose. The objective of this study was to characterize the role of DAAs in the absence of indispensable (1) AA supply in Atlantic salmon and to verify if, as in mammals they play a nutritional role under near maintenance conditions. Therefore we measured the effect of adding DAAs on nitrogen and AA...

  3. Effects of Lipolysacchride on Amino Acid Composition and Gene Expressions Related to Protein Metabolism in Milk of Dairy Cows%脂多糖对泌乳奶牛乳中氨基酸组成及蛋白质代谢相关基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    臧长江; 张养东; 王加启; 胡涛; 卜登攀; 金迪; 周凌云; 李发弟

    2012-01-01

    本试验旨在通过半体内和体外试验研究灌注脂多糖(lipopolysacchride,LPS)对泌乳奶牛乳中氨基酸组成和蛋白质代谢相关基因表达的影响.半体内试验选用6头经产的荷斯坦奶牛[泌乳天数为(186±30) d],随机分为对照组和试验组,每组3头.采用交叉试验设计,每期正试期7d,间隔期14 d;试验组阴外动脉灌注LPS(大肠杆菌型O111∶B4,0.01μg/kg),对照组阴外动脉灌注生理盐水.体外试验以乳腺上皮细胞为模型,基础培养基中LPS添加水平分别为0、0.1和10.0 ng/mL,培养24 h后,采用实时定量-PCR(qRT-PCR)法检测目的基因的相对表达水平.结果表明,阴外动脉灌注LPS后,乳中必需氨基酸、支链氨基酸含量随着灌注时间的增加呈先升高后降低的趋势(P>0.05),灌注后6h达到最高;乳中非必需氨基酸含量随着灌注时间的增加呈先降低后升高的趋势(P>0.05),灌注后6h达到最低.LPS提高了乳腺上皮细胞中p70核糖体蛋白S6激酶-1(S6K1)和真核起始因子4E结合蛋白-1(4EBP1)mRNA的表达水平(P>0.05),且具有剂量效应.LPS对雷帕霉素靶点(mTOR)、Janus激酶2(JAK2)mRNA表达水平影响差异不显著(P>0.05),但有提高的趋势.与对照组相比,LPS显著提高了信号转导和转录激活因子5(STAT5)mRNA表达水平(P<0.05).综上所述,LPS通过干扰mTOR通路和JAK2/STAT5通路影响了乳蛋白及氨基酸组成.%The objective of this experiment was to study the effects of infusion lipopolysacchride (LPS) on the amino acid composition and gene expressions related to protein metabolism in milk of dairy cows by semi in vivo and in vitro tests. Six multipara Holstein lactating cows [days in milk were (186 ±30) d] were selected in the in vivo test, and randomly divided into experimental and control groups with three cows in each group. A cross test design was applied. The test consisted of two experimental periods (7 d each) and an interval period (14 d). Cows in the

  4. Skeletal muscle metabolism in hypokinetic rats

    Science.gov (United States)

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  5. Scaffolding along Nucleic Acid Duplexes Using 2'-Amino-Locked Nucleic Acids

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Wengel, Jesper

    2014-01-01

    '-amino-LNA nucleotides. By application of different chemical reactions, modification of 2'-amino-LNA scaffolds can be efficiently performed in high yields and with various tags, postsynthetically or during the automated oligonucleotide synthesis. The choice of a synthetic method for scaffolding along 2......Conspectus Incorporation of chemically modified nucleotide scaffolds into nucleic acids to form assemblies rich in function is an innovative area with great promise for nanotechnology and biomedical and material science applications. The intrinsic biorecognition potential of nucleic acids combined......'-amino-LNA mainly depends on the chemical nature of the modification, its price, its availability, and applications of the product. One of the most useful applications of the product LNA/DNA scaffolds containing 2'-amino-LNA is to detect complementary DNA and RNA targets. Examples of these applications...

  6. Urinary excretion of amino acids during radiotherapy

    International Nuclear Information System (INIS)

    Course observations have helped to determine whether and in how far plasma and urine levels of amino acids and some other metabolites of the protein metabolism are changed by whole-body and partial irradiation. The author attempts to use combinations of these changes (e.g. increased taurine and decreased hydroxyproline levels), combined with blood plasma measurements, as indicators of radiation exposure. At the present state of the art, with deeper knowledge of the interfering influences of tumours or secondary diseases, local irradiation (radiotherapy) is a suitable test model for elaborating combinations of indicators on the basis of which even accidental radiation exposure can be detected and estimated by simple means as early as 24 to 36 h later. (orig.)

  7. Nitrogen metabolism in the ruminant

    International Nuclear Information System (INIS)

    Selected aspects of nitrogen metabolism in the ruminant are discussed. Particular attention is paid to the effect of rumen ammonia concentration on protein synthesis in the rumen. In order to judge the suitability of microbial protein as a source of protein for the ruminant, it is necessary to be able to assess the amino-acid requirements of the ruminant accurately. Several methods of doing this are discussed. Available data would indicate that under many conditions methionine is the first limiting amino acid. Possible ways of increasing the supply of methionine at the duodenum are discussed. When the amino-acid requirements are fully met, it is to be expected that protein synthesis in the tissues will proceed at its maximal rate. Ways of determining the extent of tissue protein synthesis in vivo are briefly discussed. (author)

  8. Permit application modifications

    International Nuclear Information System (INIS)

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils

  9. Environmental Modification: A Study

    Science.gov (United States)

    Grinnell, Richard M., Jr.; Kyte, Nancy S.

    1975-01-01

    This study shows that environmental modification is a surprisingly intricate technique. This may account for its relatively low use and also for its more frequent use by MSW than non-MSW caseworkers. The findings indicate the need for further research on environmental modification. (Author)

  10. Permit application modifications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

  11. Interconversions of amino acids in maturing wheat grains

    International Nuclear Information System (INIS)

    All the protein amino acids (U-14C labelled) were supplied directly to the developing spikes of spring wheat, mainly through a split stem. At maturity the proteins were fractionated into two or four Osborne fractions and the total activity was measured. The activity recovered in proteins varied from a few per cent to more than 75%. The highest recovery was found when 14C was supplied in histidine, valine, phenylalanine, leucine or tryptophan. When sugars were supplied only 3-5% of their activity was recovered in proteins, while aspartic acid, alanine, glutamic acid, proline and cysteine gave 10-20% recovery in proteins, and great respiratory losses must have occurred. The label could be transferred to every protein amino acid. Groups of amino acids showed a very similar distribution of the recovered 14C. The activity from glutamic acid, glutamine, alanine, aspartic acid and proline was mainly recovered in glutamic acid, proline and arginine, with a similar distribution for 14C transferred from lysine, isoleucine, arginine, threonine, asparagine and cysteine; however, 40-70% was recovered in the label source. Histidine, phenylalanine, leucine, tyrosine and tryptophan showed very little conversion. Activity from sugars was more spread than for amino acids. Unlabelled arginine or ornithine inhibited the conversion of glutamic acid to arginine, while lysine inhibited the conversion of aspartic acid to lysine. The results clearly indicate metabolic sites in the grain where the received amino acids are converted to amino acids that fit in with the genetic codes for specific protein synthesis. Different conversion patterns seemed to be linked to different fractions, indicating different metabolic activity in different parts of the grain and probably also in different parts of the cells in the starchy endosperm

  12. α-Amino Acid-Isosteric α-Amino Tetrazoles.

    Science.gov (United States)

    Zhao, Ting; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Herdtweck, Eberhardt; Dömling, Alexander

    2016-02-24

    The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field. PMID:26817531

  13. Lack of tRNA-i6A modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA.

    Science.gov (United States)

    Lamichhane, Tek N; Arimbasseri, Aneeshkumar G; Rijal, Keshab; Iben, James R; Wei, Fan Yan; Tomizawa, Kazuhito; Maraia, Richard J

    2016-04-01

    tRNA-isopentenyl transferases (IPTases) are highly conserved enzymes that form isopentenyl-N(6)-A37 (i6A37) on subsets of tRNAs, enhancing their translation activity. Nuclear-encoded IPTases modify select cytosolic (cy-) and mitochondrial (mt-) tRNAs. Mutation in human IPTase, TRIT1, causes disease phenotypes characteristic of mitochondrial translation deficiency due to mt-tRNA dysfunction. Deletion of the Schizosaccharomyces pombe IPTase (tit1-Δ) causes slow growth in glycerol, as well as in rapamycin, an inhibitor of TOR kinase that maintains metabolic homeostasis. Schizosaccharomyces pombe IPTase modifies three different cy-tRNAs(Ser) as well as cy-tRNA(Tyr), cy-tRNA(Trp), and mt-tRNA(Trp). We show that lower ATP levels in tit1-Δ relative to tit1(+) cells are also more decreased by an inhibitor of oxidative phosphorylation, indicative of mitochondrial dysfunction. Here we asked if the tit1-Δ phenotypes are due to hypomodification of cy-tRNA or mt-tRNA. A cytosol-specific IPTase that modifies cy-tRNA, but not mt-tRNA, fully rescues the tit1-Δ phenotypes. Moreover, overexpression of cy-tRNAs also rescues the phenotypes, and cy-tRNA(Tyr) alone substantially does so. Bioinformatics indicate that cy-tRNA(Tyr) is most limiting for codon demand in tit1-Δ cells and that the cytosolic mRNAs most loaded with Tyr codons encode carbon metabolilizing enzymes, many of which are known to localize to mitochondria. Thus, S. pombe i6A37 hypomodification-associated metabolic deficiency results from hypoactivity of cy-tRNA, mostly tRNA(Tyr), and unlike human TRIT1-deficiency does not impair mitochondrial translation due to mt-tRNA hypomodification. We discuss species-specific aspects of i6A37. Specifically relevant to mitochondria, we show that its hypermodified version, ms2i6A37 (2-methylthiolated), which occurs on certain mammalian mt-tRNAs (but not cy-tRNAs), is not found in yeast. PMID:26857223

  14. Lifestyle modifications for GDM.

    Science.gov (United States)

    Dhingra, Atul; Ahuja, Kamlesh

    2016-09-01

    Prevalence of gestational diabetes mellitus (GDM) is increasing worldwide more so in Southeast Asian countries like India and Pakistan. 1 GDM is associated with various adverse foetal and maternal effects. The management of GDM aims at reducing blood glucose to reduce maternal and foetal morbidity and mortality. Various studies have shown that lifestyle modifications are an important tool for reducing blood glucose levels in patients with GDM. Lifestyle modifications consist of dietary modifications and daily physical activity. Dietary modifications aim to achieve glycaemic control by providing adequate calories to the mother and foetus. Exercise is an obvious adjunct to dietary modifications for management of GDM. Therefore the purpose of this review is to summarize the benefits of lifestyle interventions in patients with GDM. PMID:27582149

  15. Amino Acids from a Comet

    Science.gov (United States)

    Cook, Jamie Elisla

    2009-01-01

    NASA's Stardust spacecraft returned samples from comet 81P/Wild 2 to Earth in January 2006. Examinations of the organic compounds in cometary samples can reveal information about the prebiotic organic inventory present on the early Earth and within the early Solar System, which may have contributed to the origin of life. Preliminary studies of Stardust material revealed the presence of a suite of organic compounds including several amines and amino acids, but the origin of these compounds (cometary- vs. terrestrial contamination) could not be identified. We have recently measured the carbon isotopic ratios of these amino acids to determine their origin, leading to the first detection of a coetary amino acid.

  16. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino substituted triazine amino... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  17. Metabolic ecology.

    Science.gov (United States)

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

    Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

  18. Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes

    OpenAIRE

    Jana Drgonova; Jacobsson, Josefin A.; Han, Joan C.; Yanovski, Jack A.; Robert Fredriksson; Claude Marcus; Schiöth, Helgi B; Uhl, George R.

    2013-01-01

    Brain pathways, including those in hypothalamus and nucleus of the solitary tract, influence food intake, nutrient preferences, metabolism and development of obesity in ways that often differ between males and females. Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothal...

  19. Artificial Metalloenzymes through Chemical Modification of Engineered Host Proteins

    KAUST Repository

    Zernickel, Anna

    2014-10-01

    With a few exceptions, all organisms are restricted to the 20 canonical amino acids for ribosomal protein biosynthesis. Addition of new amino acids to the genetic code can introduce novel functionalities to proteins, broadening the diversity of biochemical as well as chemical reactions and providing new tools to study protein structure, reactivity, dynamics and protein-protein-interactions. The site directed in vivo incorporation developed by P. G. SCHULTZ and coworkers, using an archeal orthogonal tRNA/aaRS (aminoacyl-tRNA synthase) pair, allows site-specifically insertion of a synthetic unnatural amino acid (UAA) by reprogramming the amber TAG stop codon. A variety of over 80 different UAAs can be introduced by this technique. However by now a very limited number can form kinetically stable bonds to late transition metals. This thesis aims to develop new catalytically active unnatural amino acids or strategies for a posttranslational modification of site-specific amino acids in order to achieve highly enantioselective metallorganic enzyme hybrids (MOEH). As a requirement a stable protein host has to be established, surviving the conditions for incorporation, posttranslational modification and the final catalytic reactions. mTFP* a fluorescent protein was genetically modified by excluding any exposed Cys, His and Met forming a variant mTFP*, which fulfills the required specifications. Posttranslational chemical modification of mTFP* allow the introduction of single site metal chelating moieties. For modification on exposed cysteines different maleiimid containing ligand structures were synthesized. In order to perform copper catalyzed click reactions, suitable unnatural amino acids (para-azido-(L)-phenylalanine, para-ethynyl-(L)-phenylalanine) were synthesized and a non-cytotoxic protocol was established. The triazole ring formed during this reaction may contribute as a moderate σ-donor/π-acceptor ligand to the metal binding site. Since the cell limits the

  20. Posttranslational Modifications of Chloroplast Proteins: An Emerging Field.

    Science.gov (United States)

    Lehtimäki, Nina; Koskela, Minna M; Mulo, Paula

    2015-07-01

    Posttranslational modifications of proteins are key effectors of enzyme activity, protein interactions, targeting, and turnover rate, but despite their importance, they are still poorly understood in plants. Although numerous reports have revealed the regulatory role of protein phosphorylation in photosynthesis, various other protein modifications have been identified in chloroplasts only recently. It is known that posttranslational N(α)-acetylation occurs in both nuclear- and plastid-encoded chloroplast proteins, but the physiological significance of this acetylation is not yet understood. Lysine acetylation affects the localization and activity of key metabolic enzymes, and it may work antagonistically or cooperatively with lysine methylation, which also occurs in chloroplasts. In addition, tyrosine nitration may help regulate the repair cycle of photosystem II, while N-glycosylation determines enzyme activity of chloroplastic carbonic anhydrase. This review summarizes the progress in the research field of posttranslational modifications of chloroplast proteins and points out the importance of these modifications in the regulation of chloroplast metabolism. PMID:25911530

  1. Trend analysis of the correlation of amino acid plasma profile with glycemic status in Saudi diabetic patients

    Directory of Open Access Journals (Sweden)

    Fahad A. Al-Abbasi

    2012-10-01

    Full Text Available The role of amino acids in diabetes mellitus and its metabolic traits have been suggested previously; however, studied to a very limited scale in the Saudi patient population. Patients diagnosed with diabetes mellitus were included in the current clinical study. Sample was representative and in accordance with the national population distribution. Blood samples were drawn and assayed for glucose, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein. General biochemical markers, such as alkaline phosphatase (ALP, creatinine kinase (CK, aspartate transaminase (AST, alanine transaminase (ALT and blood urea nitrogen (BUN were assessed. Serum amino acids of different categories (essential, semi-essential and metabolic indicator amino acids were assessed. Correlation co-efficient between each amino acid and serum glucose level was calculated. The current study showed positive correlation between amino acid level and glucose serum concentration in male while it showed negative correlation in female Saudi diabetic patients. Male patients had significantly higher methionine concentration parallel to their glycemic status. Metabolic indicator amino acids significantly changed in concordance with the glycemic status of female patients more than in male patients. In conclusion, serum amino acid is positively correlated with glycemic status in Saudi male diabetic patients while negatively correlated in female patients. Yet, further study would be recommended to utilize serum amino acid profile as surrogate parameter for the metabolic complications of diabetes mellitus.

  2. Main: Amino acid Analysis [KOME

    Lifescience Database Archive (English)

    Full Text Available Amino acid Analysis UniProt search ... blastx result Result of blastx search ... against UniProt protein ... database kome_uniprot_search _blastx_result.zip kome_uniprot_search _blastx_resul ...

  3. Main: Amino acid Analysis [KOME

    Lifescience Database Archive (English)

    Full Text Available Amino acid Analysis SwissProt search ... result Result of blastx search ... against SwissProt protein da ... tabase kome_swissprot_search _result.zip kome_swissprot_search _result ...

  4. Branched-Chain Amino Acids

    Czech Academy of Sciences Publication Activity Database

    Pátek, Miroslav

    Berlin : Springer-Verlag Berlin Heidelberg, 2007, s. 129-162. ISBN 978-3-540-48595-7 Institutional research plan: CEZ:AV0Z50200510 Keywords : amino acids * homologous reactions Subject RIV: EE - Microbiology, Virology

  5. Regulation of metabolism in Caenorhabditis elegans longevity

    OpenAIRE

    Gallo, Marco; Riddle, Donald L.

    2010-01-01

    The nematode Caenorhabditis elegans is a favorite model for the study of aging. A wealth of genetic and genomic studies show that metabolic regulation is a hallmark of life-span modulation. A recent study in BMC Biology identifying metabolic signatures for longevity suggests that amino-acid pools may be important in longevity. See research article http://www.biomedcentral.com/1741-7007/8/14.

  6. 2-Amino-5-chloropyridinium nitrate

    Directory of Open Access Journals (Sweden)

    Donia Zaouali Zgolli

    2009-11-01

    Full Text Available The title structure, C5H6ClN2+·NO3−, is held together by extensive hydrogen bonding between the NO3− ions and 2-amino-5-chloropyridinium H atoms. The cation–anion N—H...O hydrogen bonds link the ions into a zigzag- chain which develops parallel to the b axis. The structure may be compared with that of the related 2-amino-5-cyanopyridinium nitrate.

  7. Interplay between oxidant species and energy metabolism.

    Science.gov (United States)

    Quijano, Celia; Trujillo, Madia; Castro, Laura; Trostchansky, Andrés

    2016-08-01

    It has long been recognized that energy metabolism is linked to the production of reactive oxygen species (ROS) and critical enzymes allied to metabolic pathways can be affected by redox reactions. This interplay between energy metabolism and ROS becomes most apparent during the aging process and in the onset and progression of many age-related diseases (i.e. diabetes, metabolic syndrome, atherosclerosis, neurodegenerative diseases). As such, the capacity to identify metabolic pathways involved in ROS formation, as well as specific targets and oxidative modifications is crucial to our understanding of the molecular basis of age-related diseases and for the design of novel therapeutic strategies. Herein we review oxidant formation associated with the cell's energetic metabolism, key antioxidants involved in ROS detoxification, and the principal targets of oxidant species in metabolic routes and discuss their relevance in cell signaling and age-related diseases. PMID:26741399

  8. Postnatal changes of plasma amino acids in suckling pigs.

    Science.gov (United States)

    Flynn, N E; Knabe, D A; Mallick, B K; Wu, G

    2000-09-01

    Amino acids, ammonia, urea, orotate, and nitrate plus nitrite (stable oxidation products of nitric oxide) were determined in plasma of 1- to 21-d-old suckling pigs. Jugular venous blood samples were obtained from pigs at 1, 3, 7, 14, and 21 d of age for analysis of plasma amino acids and metabolites by HPLC and enzymatic methods. Plasma concentrations of arginine and its immediate precursors (citrulline and ornithine) decreased (P Plasma concentrations of glutamine declined (P Plasma concentrations of branched-chain amino acids, threonine, and alanine decreased (P changes (P > 0.05) in plasma concentrations of other amino acids. Plasma concentrations of ammonia increased (P nitric oxide synthesis, our results of the decreased plasma concentrations of arginine and nitrate plus nitrite, as well as the increased plasma ammonia concentration, indicate a hitherto unrecognized deficiency of arginine in 7- to 21-d-old suckling pigs. Arginine is an essential amino acid for piglets and has a great potential to enhance neonatal growth; therefore, further studies are necessary to elucidate the mechanism responsible for arginine deficiency in sow-reared piglets and to identify hormonal and metabolic means for improving neonatal arginine nutrition and growth. PMID:10985412

  9. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status.

    Science.gov (United States)

    Melnik, Bodo C; Schmitz, Gerd; John, Swen; Carrera-Bastos, Pedro; Lindeberg, Staffan; Cordain, Loren

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual's pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  10. Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice.

    Science.gov (United States)

    Shearn, Colin T; Fritz, Kristofer S; Shearn, Alisabeth H; Saba, Laura M; Mercer, Kelly E; Engi, Bridgette; Galligan, James J; Zimniak, Piotr; Orlicky, David J; Ronis, Martin J; Petersen, Dennis R

    2016-04-01

    Chronic alcohol consumption induces hepatic oxidative stress resulting in production of highly reactive electrophilic α/β-unsaturated aldehydes that have the potential to modify proteins. A primary mechanism of reactive aldehyde detoxification by hepatocytes is through GSTA4-driven enzymatic conjugation with GSH. Given reports that oxidative stress initiates GSTA4 translocation to the mitochondria, we hypothesized that increased hepatocellular damage in ethanol (EtOH)-fed GSTA4(-/-) mice is due to enhanced mitochondrial protein modification by reactive aldehydes. Chronic ingestion of EtOH increased hepatic protein carbonylation in GSTA4(-/-) mice as evidenced by increased 4-HNE and MDA immunostaining in the hepatic periportal region. Using mass spectrometric analysis of biotin hydrazide conjugated carbonylated proteins, a total of 829 proteins were identified in microsomal, cytosolic and mitochondrial fractions. Of these, 417 were novel to EtOH models. Focusing on mitochondrial fractions, 1.61-fold more carbonylated proteins were identified in EtOH-fed GSTA4(-)(/-) mice compared to their respective WT mice ingesting EtOH. Bioinformatic KEGG pathway analysis of carbonylated proteins from the mitochondrial fractions revealed an increased propensity for modification of proteins regulating oxidative phosphorylation, glucose, fatty acid, glutathione and amino acid metabolic processes in GSTA4(-/-) mice. Additional analysis revealed sites of reactive aldehyde protein modification on 26 novel peptides/proteins isolated from either SV/GSTA4(-/-) PF or EtOH fed mice. Among the peptides/proteins identified, ACSL, ACOX2, MTP, and THIKB contribute to regulation of fatty acid metabolism and ARG1, ARLY, and OAT, which regulate nitrogen and ammonia metabolism having direct relevance to ethanol-induced liver injury. These data define a role for GSTA4-4 in buffering hepatic oxidative stress associated with chronic alcohol consumption and that this GST isoform plays an important

  11. Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice

    Directory of Open Access Journals (Sweden)

    Colin T. Shearn

    2016-04-01

    Full Text Available Chronic alcohol consumption induces hepatic oxidative stress resulting in production of highly reactive electrophilic α/β-unsaturated aldehydes that have the potential to modify proteins. A primary mechanism of reactive aldehyde detoxification by hepatocytes is through GSTA4-driven enzymatic conjugation with GSH. Given reports that oxidative stress initiates GSTA4 translocation to the mitochondria, we hypothesized that increased hepatocellular damage in ethanol (EtOH-fed GSTA4−/− mice is due to enhanced mitochondrial protein modification by reactive aldehydes. Chronic ingestion of EtOH increased hepatic protein carbonylation in GSTA4−/− mice as evidenced by increased 4-HNE and MDA immunostaining in the hepatic periportal region. Using mass spectrometric analysis of biotin hydrazide conjugated carbonylated proteins, a total of 829 proteins were identified in microsomal, cytosolic and mitochondrial fractions. Of these, 417 were novel to EtOH models. Focusing on mitochondrial fractions, 1.61-fold more carbonylated proteins were identified in EtOH-fed GSTA4−/− mice compared to their respective WT mice ingesting EtOH. Bioinformatic KEGG pathway analysis of carbonylated proteins from the mitochondrial fractions revealed an increased propensity for modification of proteins regulating oxidative phosphorylation, glucose, fatty acid, glutathione and amino acid metabolic processes in GSTA4−/− mice. Additional analysis revealed sites of reactive aldehyde protein modification on 26 novel peptides/proteins isolated from either SV/GSTA4−/− PF or EtOH fed mice. Among the peptides/proteins identified, ACSL, ACOX2, MTP, and THIKB contribute to regulation of fatty acid metabolism and ARG1, ARLY, and OAT, which regulate nitrogen and ammonia metabolism having direct relevance to ethanol-induced liver injury. These data define a role for GSTA4-4 in buffering hepatic oxidative stress associated with chronic alcohol consumption and that this GST

  12. Surface modification of solids

    International Nuclear Information System (INIS)

    The use of ion beam and pulsed laser processing is reviewed for the near-surface modification of a wide range of materials. The techniques of ion implantation doping, ion beam and laser mixing, and pulsed-laser annealing are stressed with particular emphasis on the nonequilibrium aspects of these processing techniques and on new materials properties which can result. Examples are presented illustrating the utility of these techniques for fundamental materials research as well as practical surface modifications

  13. Quantitative proteomics by amino acid labeling identifies novel NHR-49 regulated proteins in C. elegans

    DEFF Research Database (Denmark)

    Fredens, Julius; Færgeman, Nils J.

    2012-01-01

    Stable isotope labeling by amino acids combined with mass spectrometry is a widely used methodology to quantitatively examine metabolic and signaling pathways in yeast, fruit flies, plants, cell cultures and mice. However, only metabolic labeling using (15)N has been applied to examine such events...... loss or RNAi mediated knock down of the transcription factor NHR-49, and found numerous proteins involved in lipid metabolism to be downregulated, which is consistent with its previously proposed function as a transcriptional regulator of fatty acid metabolism. The combined use of quantitative...

  14. Distinct Amino Termini of Two Human HCS Isoforms Influence Biotin Acceptor Substrate Recognition*

    OpenAIRE

    Ingaramo, Maria; Beckett, Dorothy

    2009-01-01

    The human holocarboxylase synthetase (HCS) catalyzes transfer of biotin to biotin-dependent carboxylases, and the enzyme is therefore of fundamental importance for many physiological processes, including fatty acid synthesis, gluconeogenesis, and amino acid catabolism. In addition, the enzyme functions in regulating transcription initiation at several genes that code for proteins involved in biotin metabolism. Two major forms of HCS exist in humans, which differ at the amino terminus by 57 am...

  15. Degradation of Arginine and Other Amino Acids by Eubacterium nodatum ATCC 33099

    OpenAIRE

    Uematsu, H.; Hoshino, E.

    2011-01-01

    The utilisation of a total of 20 amino acids by Eubacterium nodatum, a predominant asaccharolytic anaerobe isolated from human periodontal pockets, was studied. Washed cells of the microorganism produced substantial amounts of acetate, butyrate and ammonia from lysine, and butyrate and ammonia from arginine as main products under anaerobic conditions. They also produced a small amount of formate from histidine. Metabolic products were not detected from any of the other 17 amino acids. These r...

  16. Human Rights and Behavior Modification

    Science.gov (United States)

    Roos, Philip

    1974-01-01

    Criticisms of behavior modification, which charge that it violates ethical and legal principles, are discussed and reasons are presented to explain behavior modification's susceptibility to attack. (GW)

  17. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    . Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival, and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation...... suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells...... requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome...

  18. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  19. TISSUE SLICES IN THE STUDY OF LUNG METABOLISM AND TOXICOLOGY

    Science.gov (United States)

    Lung tissue slices are model systems for the study of pulmonary metabolism. Because of the speed and simplicity of slice preparation, lung slices have been used in studies of oxygen, amino acid, carbohydrate and lipid utilization and adenine nucleotide metabolism. Dose-response c...

  20. Interactions between epigenetics and metabolism in cancers

    Directory of Open Access Journals (Sweden)

    JihyeYun

    2012-11-01

    Full Text Available Cancer progression is accompanied by widespread transcriptional changes and metabolic alterations. Although it is widely accepted that the origin of cancer can be traced to the mutations that accumulate over time, relatively recent evidence favors a similarly fundamental role for alterations in the epigenome during tumorigenesis. Changes in epigenetics that arise from post-translational modifications of histones and DNA, are exploited by cancer cells to upregulate and/or downregulate the expression levels of oncogenes and tumor suppressors, respectively. Although the mechanisms behind these modifications, in particular how they lead to gene silencing and activation, are still being understood, many enzymes that carry out post-translational modifications that alter epigenetics require metabolites as substrates or cofactors. As a result, their activities can be influenced by the metabolic state of the cell. The purpose of this review is to give an overview of cancer epigenetics and metabolism and provide examples of where they converge.

  1. Influence of Wastewater Discharge on the Metabolic Potential of the Microbial Community in River Sediments

    KAUST Repository

    Li, Dong

    2015-09-24

    To reveal the variation of microbial community functions during water filtration process in river sediments, which has been utilized widely in natural water treatment systems, this study investigates the influence of municipal wastewater discharge to streams on the phylotype and metabolic potential of the microbiome in upstream and particularly various depths of downstream river sediments. Cluster analyses based on both microbial phylogenetic and functional data collectively revealed that shallow upstream sediments grouped with those from deeper subsurface downstream regions. These sediment samples were distinct from those found in shallow downstream sediments. Functional genes associated with carbohydrate, xenobiotic, and certain amino acid metabolisms were overrepresented in upstream and deep downstream samples. In contrast, the more immediate contact with wastewater discharge in shallow downstream samples resulted in an increase in the relative abundance of genes associated with nitrogen, sulfur, purine and pyrimidine metabolisms, as well as restriction–modification systems. More diverse bacterial phyla were associated with upstream and deep downstream sediments, mainly including Actinobacteria, Planctomycetes, and Firmicutes. In contrast, in shallow downstream sediments, genera affiliated with Betaproteobacteria and Gammaproteobacteria were enriched with putative functions that included ammonia and sulfur oxidation, polyphosphate accumulation, and methylotrophic bacteria. Collectively, these results highlight the enhanced capabilities of microbial communities residing in deeper stream sediments for the transformation of water contaminants and thus provide a foundation for better design of natural water treatment systems to further improve the removal of contaminants. © 2015, Springer Science+Business Media New York.

  2. Development of a kinetic metabolic model: application to Catharanthus roseus hairy root

    OpenAIRE

    Leduc, M.; Tikhomiroff, C.; Cloutier, M.; Perrier, M.; Jolicoeur, M.

    2006-01-01

    A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independe...

  3. Catabolism of Branched Chain Amino Acids Supports Respiration but Not Volatile Synthesis in Tomato Fruits

    Institute of Scientific and Technical Information of China (English)

    Andrej Kochevenko; Wagner L.Araújo; Gregory S.Maloney; Denise M.Tieman; Phuc Thi Do; Mark G.Taylor; Harry J.Klee; Alisdair R.Fernie

    2012-01-01

    The branched-chain amino acid transaminases (BCATs) have a crucial role in metabolism of the branched-chain amino acids leucine,isoleucine,and valine.These enzymes catalyze the last step of synthesis and the initial step of degradation of these amino acids.Although the biosynthetic pathways of branched chain amino acids in plants have been extensively investigated and a number of genes have been characterized,their catabolism in plants is not yet completely understood.We previously characterized the branched chain amino acid transaminase gene family in tomato,revealing both the subcellular localization and kinetic properties of the enzymes encoded by six genes.Here,we examined possible functions of the enzymes during fruit development.We further characterized transgenic plants differing in the expression of branched chain amino acid transaminases 1 and 3,evaluating the rates of respiration in fruits deficient in BCAT1 and the levels of volatiles in lines overexpressing either BCAT1 or BCAT3.We quantitatively tested,via precursor and isotope feeding experiments,the importance of the branched chain amino acids and their corresponding keto acids in the formation of fruit volatiles.Our results not only demonstrate for the first time the importance of branched chain amino acids in fruit respiration,but also reveal that keto acids,rather than amino acids,are the likely precursors for the branched chain flavor volatiles.

  4. DRUG METABOLISM

    Directory of Open Access Journals (Sweden)

    Deepak Singla

    2011-02-01

    Full Text Available The termmetabolism, derived from the Greek language, simply means change or transformation. It relates to various processes within the body that convert food and other substances into energy and other metabolic byproducts used by the body. Drug metabolism is the body’s way of transforming drugs, so they can be excreted from the body. Many drugs arenot active until they have been metabolized in the body by enzymes that transform them. Most drugs are lipophilic, meaning they pass through membranes to reach their target site. Most drugs are treated by the body like foreign substances, also known as xenobiotics. Humans have evolved a complex system for xenobiotic metabolism

  5. Metabolic neuropathies

    Science.gov (United States)

    ... body ( sepsis ) Thyroid disease Vitamin deficiencies (including vitamins B12 , B6 , E , and B1 ) Some metabolic disorders are ... by injection. Abnormal blood sugar level or thyroid function may need medicines to correct the problem. For ...

  6. Metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gogia Atul

    2006-02-01

    Full Text Available The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entitiy. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes, hypertriglyceridemia, hypertension, polycystic ovary yndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely

  7. Lipid Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  8. Animal metabolism

    International Nuclear Information System (INIS)

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  9. Amino acid starvation has opposite effects on mitochondrial and cytosolic protein synthesis.

    Directory of Open Access Journals (Sweden)

    Mark A Johnson

    Full Text Available Amino acids are essential for cell growth and proliferation for they can serve as precursors of protein synthesis, be remodelled for nucleotide and fat biosynthesis, or be burnt as fuel. Mitochondria are energy producing organelles that additionally play a central role in amino acid homeostasis. One might expect mitochondrial metabolism to be geared towards the production and preservation of amino acids when cells are deprived of an exogenous supply. On the contrary, we find that human cells respond to amino acid starvation by upregulating the amino acid-consuming processes of respiration, protein synthesis, and amino acid catabolism in the mitochondria. The increased utilization of these nutrients in the organelle is not driven primarily by energy demand, as it occurs when glucose is plentiful. Instead it is proposed that the changes in the mitochondrial metabolism complement the repression of cytosolic protein synthesis to restrict cell growth and proliferation when amino acids are limiting. Therefore, stimulating mitochondrial function might offer a means of inhibiting nutrient-demanding anabolism that drives cellular proliferation.

  10. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    International Nuclear Information System (INIS)

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  11. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (China); Zhao Jing [China Institute of Atomic Energy (China); Hao Fuhua [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (China); Chen Chang [Institute of Biophysics, The Chinese Academy of Sciences, National Laboratory of Biomacromolecules (China); Bhakoo, Kishore [Singapore Bioimaging Consortium Agency for Science, Technology and Research (A-STAR) (Singapore); Tang, Huiru, E-mail: huiru.tang@wipm.ac.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (China)

    2011-05-15

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  12. Readers of PCNA modifications.

    Science.gov (United States)

    Ulrich, Helle D; Takahashi, Tomio

    2013-08-01

    The eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), acts as a central coordinator of DNA transactions by providing a multivalent interaction surface for factors involved in DNA replication, repair, chromatin dynamics and cell cycle regulation. Posttranslational modifications (PTMs), such as mono- and polyubiquitylation, sumoylation, phosphorylation and acetylation, further expand the repertoire of PCNA's binding partners. These modifications affect PCNA's activity in the bypass of lesions during DNA replication, the regulation of alternative damage processing pathways such as homologous recombination and DNA interstrand cross-link repair, or impact on the stability of PCNA itself. In this review, we summarise our current knowledge about how the PTMs are "read" by downstream effector proteins that mediate the appropriate action. Given the variety of interaction partners responding to PCNA's modified forms, the ensemble of PCNA modifications serves as an instructive model for the study of biological signalling through PTMs in general. PMID:23580141

  13. Structural dynamic modification

    Indian Academy of Sciences (India)

    A Sestieri

    2000-06-01

    Vibration and acoustic requirements are becoming increasingly important in the design of mechanical structures, but they are not usually of primary concern in the design process. So the need to vary the structural behaviour to solve noise and vibration problems often occurs at the prototype stage, giving rise to the so-called structural modification problem. In this paper, the direct problem of determing the new response of a system, after some modifications are introduced into the sestem, is analysed using two different databases: the modal database and the frequency response function database. The limitaions of the modal database are discussed. Structural modifications that can be accounted for are lumped masses, springs, dampers and dynamic absorbers.

  14. Genome-scale reconstruction of Salinispora tropica CNB-440 metabolism to study strain-specific adaptation.

    Science.gov (United States)

    Contador, C A; Rodríguez, V; Andrews, B A; Asenjo, J A

    2015-11-01

    The first manually curated genome-scale metabolic model for Salinispora tropica strain CNB-440 was constructed. The reconstruction enables characterization of the metabolic capabilities for understanding and modeling the cellular physiology of this actinobacterium. The iCC908 model was based on physiological and biochemical information of primary and specialised metabolism pathways. The reconstructed stoichiometric matrix consists of 1169 biochemical conversions, 204 transport reactions and 1317 metabolites. A total of 908 structural open reading frames (ORFs) were included in the reconstructed network. The number of gene functions included in the reconstructed network corresponds to 20% of all characterized ORFs in the S. tropica genome. The genome-scale metabolic model was used to study strain-specific capabilities in defined minimal media. iCC908 was used to analyze growth capabilities in 41 different minimal growth-supporting environments. These nutrient sources were evaluated experimentally to assess the accuracy of in silico growth simulations. The model predicted no auxotrophies for essential amino acids, which was corroborated experimentally. The strain is able to use 21 different carbon sources, 8 nitrogen sources and 4 sulfur sources from the nutrient sources tested. Experimental observation suggests that the cells may be able to store sulfur. False predictions provided opportunities to gain new insights into the physiology of this species, and to gap fill the missing knowledge. The incorporation of modifications led to increased accuracy in predicting the outcome of growth/no growth experiments from 76 to 93%. iCC908 can thus be used to define the metabolic capabilities of S. tropica and guide and enhance the production of specialised metabolites. PMID:26459337

  15. Physical activity in obesity and metabolic syndrome

    OpenAIRE

    Strasser, Barbara

    2012-01-01

    Biological aging is typically associated with a progressive increase in body fat mass and a loss of lean body mass. Owing to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Lifestyle modification, specifically changes in diet, physical activity, and exercise, is considered the cornerstone of obesity management. However, for most overweight people it is difficult to ...

  16. Predicting lysine phosphoglycerylation with fuzzy SVM by incorporating k-spaced amino acid pairs into Chou׳s general PseAAC.

    Science.gov (United States)

    Ju, Zhe; Cao, Jun-Zhe; Gu, Hong

    2016-05-21

    As a new type of post-translational modification, lysine phosphoglycerylation plays a key role in regulating glycolytic process and metabolism in cells. Due to the traditional experimental methods are time-consuming and labor-intensive, it is important to develop computational methods to identify the potential phosphoglycerylation sites. However, the prediction performance of the existing phosphoglycerylation site predictor is not satisfactory. In this study, a novel predictor named CKSAAP_PhoglySite is developed to predict phosphoglycerylation sites by using composition of k-spaced amino acid pairs and fuzzy support vector machine. On the one hand, after many aspects of assessments, we find the composition of k-spaced amino acid pairs is more suitable for representing the protein sequence around the phosphoglycerylation sites than other encoding schemes. On the other hand, the proposed fuzzy support vector machine algorithm can effectively handle the imbalanced and noisy problem in phosphoglycerylation sites training dataset. Experimental results indicate that CKSAAP_PhoglySite outperforms the existing phosphoglycerylation site predictor Phogly-PseAAC significantly. A matlab software package for CKSAAP_PhoglySite can be freely downloaded from https://github.com/juzhe1120/Matlab_Software/blob/master/CKSAAP_PhoglySite_Matlab_Software.zip. PMID:26908349

  17. Combinatorics of aliphatic amino acids.

    Science.gov (United States)

    Grützmann, Konrad; Böcker, Sebastian; Schuster, Stefan

    2011-01-01

    This study combines biology and mathematics, showing that a relatively simple question from molecular biology can lead to complicated mathematics. The question is how to calculate the number of theoretically possible aliphatic amino acids as a function of the number of carbon atoms in the side chain. The presented calculation is based on earlier results from theoretical chemistry concerning alkyl compounds. Mathematical properties of this number series are highlighted. We discuss which of the theoretically possible structures really occur in living organisms, such as leucine and isoleucine with a chain length of four. This is done both for a strict definition of aliphatic amino acids only involving carbon and hydrogen atoms in their side chain and for a less strict definition allowing sulphur, nitrogen and oxygen atoms. While the main focus is on proteinogenic amino acids, we also give several examples of non-proteinogenic aliphatic amino acids, playing a role, for instance, in signalling. The results are in agreement with a general phenomenon found in biology: Usually, only a small number of molecules are chosen as building blocks to assemble an inconceivable number of different macromolecules as proteins. Thus, natural biological complexity arises from the multifarious combination of building blocks. PMID:21120449

  18. Organic modification of carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The organic modification of carbon nanotubes is a novel research field being developed recently. In this article, the history and newest progress of organic modification of carbon nanotubes are reviewed from two aspects:organic covalent modification and organic noncovalent modification of carbon nanotubes. The preparation and properties of organic modified carbon nanotubes are discussed in detail. In addition, the prospective development of organic modification of carbon nanotubes is suggested.

  19. A guide to tropical modifications

    OpenAIRE

    Kalinin, Nikita

    2015-01-01

    This chapter is dedicated to {\\it tropical modifications}, which have already become a folklore in tropical geometry. Tropical modifications are used in tropical intersection theory, the study of singularities, and admit interpretations in various contexts, such as hyperbolic geometry, Berkovich spaces, and non-standard analysis. One must say that the name "modification" is used in two different senses: the modification as a well-defined {\\it operation}, and a modification along $X$ as a {\\it...

  20. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders.......DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...

  1. Protein modification by acrolein: Formation and stability of cysteine adducts

    OpenAIRE

    Cai, Jian; Bhatnagar, Aruni; Pierce, William M.

    2009-01-01

    The toxicity of the ubiquitous pollutant and endogenous metabolite, acrolein, is due in part to covalent protein modifications. Acrolein reacts readily with protein nucleophiles via Michael addition and Schiff base formation. Potential acrolein targets in protein include the nucleophilic side chains of cysteine, histidine, and lysine residues as well as the free amino terminus of proteins. Although cysteine is the most acrolein-reactive residue, cysteine-acrolein adducts are difficult to iden...

  2. Personalizing Behavior Modification.

    Science.gov (United States)

    White, Debra G.; And Others

    1987-01-01

    Process reinforcement is proposed as a reinforcement method that is more comfortable, personal, comprehensive, and interactive than traditional behavior modification. Process reinforcement strengthens desired behaviors by engaging learners in a one-on-one examination of how they achieved correct responses and by practicing comfortable eye contact…

  3. Defining Behavior Modification

    Science.gov (United States)

    Christoplos, Florence; Valletutti, Peter

    1969-01-01

    Discusses the proposition that: "The educational problem involved in behavior modification, in the evaluationand measurement of learning, is the integration and coordination of three types of information affecting the achievement of specific behavioral goals: (1) information about the child, (2) information about the task, and (3) information…

  4. Biblical behavior modification.

    Science.gov (United States)

    Lasure, L C; Mikulas, W L

    1996-07-01

    Although we may have formalized and systematized the field of behavior modification in the last few decades, people around the world have been using behavioral change strategies throughout history. Premack's (1965) theory of reinforcement is often called "Grandma's rule" because grandmothers have long been using it (e.g. You must finish your vegetables before you may go out and play). Franks (1969, p. 4), in one of the first behavioral texts, gave historical examples from China, Turkey, France, and Italy. Knapp and Shodahl (1974) showed how Benjamin Franklin used behavior modification. And de Silva (1984, 1985) gave examples of behavior modification by the Buddha and other early Buddhists. Conspicuously absent from our literature are examples from the Judeo-Christian tradition. In this paper, we provide a number of behavior modification examples from the Bible (New International Version). Footnotes provide references for many more examples. In the discussion, we explore implications for education and therapy. Examples are grouped by the following categories: operant conditioning, respondent conditioning, modeling, and cognitive interventions. However, the Biblical examples, like contemporary case studies, do not always fall neatly into discrete categories. They often are a combination, particularly operant and respondent conditioning interweaving. PMID:8826763

  5. Modifications of Paroemia Invariants

    Directory of Open Access Journals (Sweden)

    Taliya F. Pecherskikh

    2013-01-01

    Full Text Available The phenomenon of modifications of paroemia invariants proves that language constantly changes and develops. The realization of communication need through the new evocative forms of expression is generality of the opposite linguistic phenomena of occasional variants of paroemia, aimed at the establishment of equilibrium in phraseology.

  6. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.;

    2010-01-01

    constitutively expressed protein isoforms, which were associated with 203 ORFs in the A. balhimycina genome. These data, providing insights on the major metabolic pathways/molecular processes operating in this organism, were used to compile 2-DE reference maps covering 3-10, 4-7 and 4.5-5.5 pH gradients...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis......, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhimycin precursors, such as amino acids, amino sugars and central carbon metabolism...

  7. The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy

    Directory of Open Access Journals (Sweden)

    Yangzom D. Bhutia

    2014-12-01

    Full Text Available Tumor cells have an increased demand for glucose and amino acids to support their rapid growth, and also exhibit alterations in biochemical pathways that metabolize these nutrients. Transport across the plasma membrane is essential to feed glucose and amino acids into these tumor cell-selective metabolic pathways. Transfer of amino acids across biological membranes occurs via a multitude of transporters; tumor cells must upregulate one or more of these transporters to satisfy their increased demand for amino acids. Among the amino acid transporters, SLC6A14 stands out with specific functional features uniquely suited for the biological needs of the tumor cells. This transporter is indeed upregulated in tumors of epithelial origin, including colon cancer, cervical cancer, breast cancer, and pancreatic cancer. Since normal cells express this transporter only at low levels, blockade of this transporter should lead to amino acid starvation selectively in tumor cells, thus having little effect on normal cells. This offers a novel, yet logical, strategy for the treatment of cancers that are associated with upregulation of SLC6A14. In addition, a variety of amino acid-based prodrugs are recognized as substrates by SLC6A14, thus raising the possibility that anticancer drugs can be delivered into tumor cells selectively via this transporter in the form of amino acid prodrugs. This strategy allows exposure of SLC6A14-positive tumor cells to chemotherapy with minimal off-target effects. In conclusion, the amino acid transporter SLC6A14 holds great potential not only as a direct drug target for cancer therapy but also for tumor cell-selective delivery of anticancer drugs.

  8. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    Science.gov (United States)

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  9. Chronophysiological modifications of the triiodothyronine's peripheral metabolism(T3)

    International Nuclear Information System (INIS)

    An interesting aspect relative to the thyroid function consists in determining the variations produced by the age. Though this relation has been referred to T4 related with age, there are no differences about T3 kinetics. For this purpose, different parameters were studied in 68 euthyroid controls of both sexs, in good nutritional state and normal activity, whose ages oscillate between 6 and 83 years old. A kinetic study method of single i.v. T3-I125 injection was used, employing 0,5 μCi/Kg of body weight with maximum activity of 10 μCi to 10 years old; 15 μCi to 15 years old and 30 μCi above this age. Determinations of T4, T3 and TSH serum by radioimmunoassay were carried out. From these studies, the following conclusions were obtained: T4 and TSH are within the normal values, while a decrease of T3 related with age was observed. Parallely to said decrease, a prolongation of plasmatic half time and a decrease of the daily value production, which is expressed statistically by a double exponential function are appreciated. The first one, which is of fast slope, corresponds to subjects below 10 years old and the second one, which is slower, starts from that age to the seventh decade of life. (M.E.L.)

  10. Nitrate metabolism in tobacco leaves overexpressing Arabidopsis nitrite reductase.

    Science.gov (United States)

    Davenport, Susie; Le Lay, Pascaline; Sanchez-Tamburrrino, Juan Pablo

    2015-12-01

    Primary nitrogen assimilation in plants includes the reduction of nitrite to ammonium in the chloroplasts by the enzyme nitrite reductase (NiR EC:1.7.7.1) or in the plastids of non-photosynthetic organs. Here we report on a study overexpressing the Arabidopsis thaliana NiR (AtNiR) gene in tobacco plants under the control of a constitutive promoter (CERV - Carnation Etched Ring Virus). The aim was to overexpress AtNiR in an attempt to alter the level of residual nitrite in the leaf which can act as precursor to the formation of nitrosamines. The impact of increasing the activity of AtNiR produced an increase in leaf protein and a stay-green phenotype in the primary transformed AtNiR population. Investigation of the T1 homozygous population demonstrated elevated nitrate reductase (NR) activity, reductions in leaf nitrite and nitrate and the amino acids proline, glutamine and glutamate. Chlorophyl content of the transgenic lines was increased, as evidenced by the stay-green phenotype. This reveals the importance of NiR in primary nitrogen assimilation and how modification of this key enzyme affects both the nitrogen and carbon metabolism of tobacco plants. PMID:26447683

  11. [Inherited amino acid transport disorders].

    Science.gov (United States)

    Igarashi, Y; Tada, K

    1992-07-01

    Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush-border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia-hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders. PMID:1404888

  12. Metabolic Syndrome

    Science.gov (United States)

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  13. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  14. Metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Charles Shaeffer

    2004-01-01

    @@ The emergence of cardiac disease as the number one world-wide cause of death justifies efforts to identify individuals at higher risk for preventive therapy. The metabolic syndrome, originally described by Reaven, 1 has been associated with higher cardiovascular disease risk. 2 Type Ⅱ diabetes is also a frequent sequela. 3

  15. Isotachophoretic determination of basic amino acids: arginine, histidine and lysine in real matrix

    Czech Academy of Sciences Publication Activity Database

    Herrmannová, Michaela; Křivánková, Ludmila; Bartoš, M.; Vytřas, K.

    Pardubice: Univezita Pardubice, 2006 - (Blattná, J.; Horna, A.; Zima, T.). s. 199-200 ISBN 80-7194-855-1. [Vitamins 2006. International Conference /6./. Health Ingredients Metabolism Analysis.. 10.09.2006-16.09.2006, Pardubice] R&D Projects: GA ČR GA203/05/2106 Keywords : isotachophoresis * amino acid Subject RIV: CB - Analytical Chemistry, Separation

  16. 4-Amino­phthalimide

    OpenAIRE

    Sarkar, Moloy

    2008-01-01

    The mol­ecules in the title compound (systematic name: 5-aminoisoindole-1,3-dione), C8H6N2O2, are packed through N—H⋯O inter­molecular hydrogen-bonding inter­actions. Two types of hydrogen bonds are observed: one, involving the imide group, forms mol­ecular chains along the c axis and another two, involving the amino group, connect the mol­ecular chains.

  17. Enzymatic modification of starch

    DEFF Research Database (Denmark)

    Jensen, Susanne Langgård

    In the food industry approaches for using bioengineering are investigated as alternatives to conventional chemical and physical starch modification techniques in development of starches with specific properties. Enzyme-assisted post-harvest modification is an interesting approach to this, since it...... is considered a clean and energy saving technology. This thesis aimed to investigate the effect of using reaction conditions, simulating an industrial process, for enzymatic treatment of starch with branching enzyme (BE) from Rhodothermus obamensis. Thus treatements were conducted at 70°C using very...... high substrate concentration (30-40% dry matter (DM)) and high enzyme activity (750-2250 BE units (BEU)/g sample). Starches from various botanical sources, representing a broad range of properties, were used as substrates. The effects of the used conditions on the BE-reaction were evaluated by...

  18. PES fabric plasma modification

    Science.gov (United States)

    Vatuňa, T.; Špatenka, P.; Píchal, J.; Koller, J.; Aubrecht, L.; Wiener, J.

    2004-03-01

    Polyester ranks the upper position in the world fiber production — nearly 54% of the total production of synthetic fibers. Troubles connected with minimizing of the textile hydrophobicity are usually being solved by the textile fibers’ surface chemical modification, but from ecological point of view modification of fabric with low temperature plasma is superior to classical chemical wet processes. Application of various plasmas for PES treatment has been already described. To compare the effectiveness of different plasma sources we performed a series of experiment both in RF and MW plasmas. For working gas nitrogen, oxygen and their mixtures were employed. Internal plasma control was provided by measurement of optical emission spectra. The hydrophilicity degree was determined by the drop test. Paper discusses optimal conditions of the PES fabric plasma treatment.

  19. Geometrically Consistent Mesh Modification

    KAUST Repository

    Bonito, A.

    2010-01-01

    A new paradigm of adaptivity is to execute refinement, coarsening, and smoothing of meshes on manifolds with incomplete information about their geometry and yet preserve position and curvature accuracy. We refer to this collectively as geometrically consistent (GC) mesh modification. We discuss the concept of discrete GC, show the failure of naive approaches, and propose and analyze a simple algorithm that is GC and accuracy preserving. © 2010 Society for Industrial and Applied Mathematics.

  20. Synthesis of Chiral Amino Cyclic Phosphoric Acids

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Chirai amino cyclic phosphoric acids, 5-amino-2-hydroxy-4- (4-nitrophenyl)-l, 3,2-dioxaphospho- rinane 2-oxide and 2-hydroxy-4- (4-methylsulfonylphenyl)-5-phthalimido-1,3,2-dioxaphos phorinane 2-oxide are synthesized in good over yields (64. 2% and 72. 8% respectively) from 2-amino-l-aryl-l,3-propanediols. The different reaction conditions are necessary in hydrolysis reactions of amino cyclic phosphonyl chlorides.

  1. Unnatural reactive amino acid genetic code additions

    Energy Technology Data Exchange (ETDEWEB)

    Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

    2013-05-21

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  2. Unnatural reactive amino acid genetic code additions

    Energy Technology Data Exchange (ETDEWEB)

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2014-08-26

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  3. Improvement of activity and stability of chloroperoxidase by chemical modification

    Directory of Open Access Journals (Sweden)

    Wang Min

    2007-05-01

    Full Text Available Abstract Background Enzymes show relative instability in solvents or at elevated temperature and lower activity in organic solvent than in water. These limit the industrial applications of enzymes. Results In order to improve the activity and stability of chloroperoxidase, chloroperoxidase was modified by citraconic anhydride, maleic anhydride or phthalic anhydride. The catalytic activities, thermostabilities and organic solvent tolerances of native and modified enzymes were compared. In aqueous buffer, modified chloroperoxidases showed similar Km values and greater catalytic efficiencies kcat/Km for both sulfoxidation and oxidation of phenol compared to native chloroperoxidase. Of these modified chloroperoxidases, citraconic anhydride-modified chloroperoxidase showed the greatest catalytic efficiency in aqueous buffer. These modifications of chloroperoxidase increased their catalytic efficiencies for sulfoxidation by 12%~26% and catalytic efficiencies for phenol oxidation by 7%~53% in aqueous buffer. However, in organic solvent (DMF, modified chloroperoxidases had lower Km values and higher catalytic efficiencies kcat/Km than native chloroperoxidase. These modifications also improved their thermostabilities by 1~2-fold and solvent tolerances of DMF. CD studies show that these modifications did not change the secondary structure of chloroperoxidase. Fluorescence spectra proved that these modifications changed the environment of tryptophan. Conclusion Chemical modification of epsilon-amino groups of lysine residues of chloroperoxidase using citraconic anhydride, maleic anhydride or phthalic anhydride is a simple and powerful method to enhance catalytic properties of enzyme. The improvements of the activity and stability of chloroperoxidase are related to side chain reorientations of aromatics upon both modifications.

  4. Multipolar Electrostatic Energy Prediction for all 20 Natural Amino Acids Using Kriging Machine Learning.

    Science.gov (United States)

    Fletcher, Timothy L; Popelier, Paul L A

    2016-06-14

    A machine learning method called kriging is applied to the set of all 20 naturally occurring amino acids. Kriging models are built that predict electrostatic multipole moments for all topological atoms in any amino acid based on molecular geometry only. These models then predict molecular electrostatic interaction energies. On the basis of 200 unseen test geometries for each amino acid, no amino acid shows a mean prediction error above 5.3 kJ mol(-1), while the lowest error observed is 2.8 kJ mol(-1). The mean error across the entire set is only 4.2 kJ mol(-1) (or 1 kcal mol(-1)). Charged systems are created by protonating or deprotonating selected amino acids, and these show no significant deviation in prediction error over their neutral counterparts. Similarly, the proposed methodology can also handle amino acids with aromatic side chains, without the need for modification. Thus, we present a generic method capable of accurately capturing multipolar polarizable electrostatics in amino acids. PMID:27224739

  5. Evolutionary programming as a platform for in silico metabolic engineering

    OpenAIRE

    Förster Jochen; Rocha Isabel; Patil Kiran; Nielsen Jens

    2005-01-01

    Abstract Background Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms...

  6. Metabolic effects of CO2 anaesthesia in Drosophila melanogaster

    OpenAIRE

    Colinet, H.; Renault, D.

    2012-01-01

    Immobilization of insects is necessary for various experimental purposes, and CO2 exposure remains the most popular anaesthetic method in entomological research. A number of negative side effects of CO2 anaesthesia have been reported, but CO2 probably brings about metabolic modifications that are poorly known. In this work, we used GC/MS-based metabolic fingerprinting to assess the effect of CO2 anaesthesia in Drosophila melanogaster adults. We analysed metabolic variation of flies submitted ...

  7. Effect of dietary starch level and high rumen-undegradable protein on endocrine-metabolic status, milk yield, and milk composition in dairy cows during early and late lactation.

    Science.gov (United States)

    Piccioli-Cappelli, F; Loor, J J; Seal, C J; Minuti, A; Trevisi, E

    2014-12-01

    Diet composition defines the amount and type of nutrients absorbed by dairy cows. Endocrine-metabolic interactions can influence these parameters, and so nutrient availability for the mammary gland can significantly vary and affect milk yield and its composition. Six dairy cows in early and then late lactation received, for 28 d in a changeover design, 2 diets designed to provide, within the same stage of lactation, similar amounts of rumen fermentable material but either high starch plus sugar (HS) content or low starch plus sugar content (LS). All diets had similar dietary crude protein and calculated supply of essential amino acids. Dry matter intake within each stage of lactation was similar between groups. Milk yield was similar between groups in early lactation, whereas a higher milk yield was observed in late lactation when feeding HS. At the metabolic level, the main difference observed between the diets in both stages of lactation was lower blood glucose in cows fed LS. The lower glucose availability during consumption of LS caused substantial modifications in the circulating and postprandial pattern of metabolic hormones. Feeding LS versus HS resulted in an increase in the ratio of bovine somatotropin to insulin. This increased mobilization of lipid reserves resulted in higher blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, which contributed to the higher milk fat content in both stages of lactation in the LS group. This greater recourse to body fat stores was confirmed by the greater loss of body weight during early lactation and the slower recovery of body weight in late lactation in cows fed LS. The lower insulin to glucagon ratio observed in cows fed LS in early and late lactation likely caused an increase in hepatic uptake and catabolism of amino acids, as confirmed by the higher blood urea concentrations. Despite the higher catabolism of amino acids in LS in early lactation, similar milk protein output was observed for both

  8. Metabolic Syndrome: Hyperlipidemia.

    Science.gov (United States)

    Bragg, Dee Ann Stults; Walling, Anne

    2015-08-01

    Metabolic syndrome is associated with an elevated risk of cardiovascular disease and premature mortality. When metabolic syndrome includes lipid abnormalities, management goals are weight loss and cardiovascular risk management through lifestyle modifications (eg, diet, exercise), and, when appropriate, lowering of lipid levels with pharmacotherapy. Healthy diets are recommended, particularly the Mediterranean diet. Patients also should set a goal of at least 30 minutes of moderate to vigorous exercise on most, preferably all, days of the week. Guidelines provide criteria for statin treatment based on overall cardiovascular risk. High-intensity statin treatment (eg, rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg) typically is recommended unless the patient cannot tolerate therapy. Approximately 5% of patients experience statin-induced myalgia, in which case moderate-intensity treatment can be tried. Lipid levels should be reevaluated 4 to 12 weeks after initiating therapy; lipid levels can be measured without fasting. A lack of improvement often indicates nonadherence. Bile acid sequestrants, fibric acids, and niacin can be used if other drugs are not tolerated. The evidence to support use of integrative medicine is limited, but the strongest evidence of benefit is for garlic (Allium sativum). PMID:26280341

  9. Strategies for comprehensive analysis of amino acid biomarkers of oxidative stress.

    Science.gov (United States)

    Ptolemy, A S; Lee, R; Britz-McKibbin, P

    2007-07-01

    Despite the wide interest in using modified amino acids as putative biomarkers of oxidative stress, many issues remain as to their overall reliability for early detection and diagnosis of diseases. In contrast to conventional single biomarker studies, comprehensive analysis of biomarkers offers an unbiased strategy for global assessment of modified amino acid metabolism due to reactive oxygen and nitrogen species. This review examines recent analytical techniques amenable for analysis of modified amino acids in biological samples reported during 2003-2007. Particular attention is devoted to the need for validated methods applicable to high-throughput analysis of multiple amino acid biomarkers, as well as consideration of sample pretreatment protocols on artifact formation for improved clinical relevance. PMID:17514495

  10. β-N-methylamino-L-alanine (BMAA) metabolism in the aquatic macrophyte Ceratophyllum demersum.

    Science.gov (United States)

    Downing, Simoné; Esterhuizen-Londt, Maranda; Grant Downing, Timothy

    2015-10-01

    The cyanobacterial neurotoxin, β-N-methylamino-l-alanine (BMAA) bioaccumulates and biomagnifies within the environment. However, most reports on the environmental presence of BMAA focus on the presence of BMAA in animals rather than in plants. Various laboratory studies have reported that this neurotoxin, implicated in neurodegenerative disease, is rapidly taken up by various aquatic and terrestrial plants, including crop plants. In this study the metabolism of BMAA in the aquatic macrophyte, Ceratophyllum demersum, was investigated using stable isotopically labelled BMAA. Data show that the toxin is rapidly removed from the environment by the plant. However, during depuration cellular BMAA concentrations decrease considerably, without excretion of the toxin back into the environment and without catabolism of BMAA, evidenced by the absence of label transfer to other amino acids. This strongly suggests that BMAA is metabolised via covalent modification and sequestered inside the plant as a BMAA-derivative. This modification may be reversed in humans following consumption of BMAA-containing plant material. These data therefore impact on the assessment of the risk of human exposure to this neurotoxin. PMID:26036420

  11. Towards a metabolic therapy of cancer?

    Science.gov (United States)

    Chiu, Martina; Ottaviani, Laura; Bianchi, Massimiliano G; Franchi-Gazzola, Renata; Bussolati, Ovidio

    2012-12-01

    It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely, mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only "metabolic" drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs. PMID:23762991

  12. Amino acid properties conserved in molecular evolution.

    Directory of Open Access Journals (Sweden)

    Witold R Rudnicki

    Full Text Available That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts - one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications.

  13. Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

    International Nuclear Information System (INIS)

    BPA used in BNCT has a similar structure to some essential amino acids and is transported into tumor cells by amino acid transport systems. Previous study groups have tried various techniques of loading BPA to increase intracellular boron concentration. CHO-K1 cells demonstrate system L (LAT1) activity and are suitable for specifying the transport system of a neutral amino acid. In this study, we examined the intracellular accumulation of boron in CHO-K1 cells by amino acid transport control, which involves co-loading with L-type amino acid esters. Intracellular boron accumulation in CHO-K1 cells showed the greatest increased upon co-loading 1.0 mM BPA, with 1.0 mM L-Tyr-O-Et and incubating for 60 min. This increase is caused by activation of a system L amino acid exchanger between BPA and L-Tyr. The amino acid esters are metabolized to amino acids by intracellular hydrolytic enzymes that increase the concentrations of intracellular amino acids and stimulate exchange transportation. We expect that this amino acid transport control will be useful for enhancing intracellular boron accumulation. - Highlights: • We examined optimal L-p-boronophenylalanine (BPA) loading in CHO-K1 cells. • Optimal BPA loading parameters were 1.0 mM and incubation for 60 min. • Intracellular boron accumulation increased upon co-loading BPA with L-Tyr-O-Et. • Optimal L-Tyr-O-Et loading parameters were 1.0 mM and incubation for 60 min. • Co-loading BPA with L-Tyr-O-Et can increase intracellular boron accumulation

  14. Utilization of alimentary protein and amino acids in satisfying the nitrogen requirements of monogastric mammals

    International Nuclear Information System (INIS)

    The nitrogenous matter in the food of monogastric animals consists mainly of proteins, which are rapidly hydrolized in the intestinal tract when they have left the gastric reservoir. The digestive tube has several roles: it provides for hydrolysis of the food proteins and for a supply of endogenous nitrogen; it enables a certain digestive function to be performed by the intestinal flora and permits the transport of amino acids into the blood, selecting those which are needed for protein synthesis. The digestion products appear mainly in the form of free amino acids in the portal blood. A large proportion of these amino acids is taken up by the liver, so that intense protein synthesis takes place in the latter, coupled with a decrease in catabolism leading to a rhythmic increase in the liver content of proteins and RNA. The labile proteins retained are mainly enzymes, which catabolize the amino acids, and the liver is the site of the catabolism of most of the excess amino acids except those with chain branching. Alimentary deficiencies do not markedly reduce protein synthesis in this organ, since the rate of re-utilization of the amino acids is increased and the liver thus plays a regulatory role. The utilization of amino acids in muscle also follows a certain rhythm, partly connected with feeding, and under hormonal control. The muscle is the seat of catabolism of a large part of the branched chain amino acids, and like the liver it contributes to the energy utilization of amino acids. The rate of utilization of certain essential amino acids can be measured by metabolic criteria, including determination of blood and muscle concentrations and excretion of 14CO2 labels in the exhaled air or of 35S labels in urine. (author)

  15. Pairwise amino acid secondary structural propensities

    Science.gov (United States)

    Chemmama, Ilan E.; Chapagain, Prem P.; Gerstman, Bernard S.

    2015-04-01

    We investigate the propensities for amino acids to form a specific secondary structure when they are paired with other amino acids. Our investigations use molecular dynamics (MD) computer simulations, and we compare the results to those from the Protein Data Bank (PDB). Proper comparison requires weighting of the MD results in a manner consistent with the relative frequency of appearance in the PDB of each possible pair of amino acids. We find that the propensity for an amino acid to assume a secondary structure varies dramatically depending on the amino acid that is before or after it in the primary sequence. This cooperative effect means that when selecting amino acids to facilitate the formation of a secondary structure in peptide engineering experiments, the adjacent amino acids must be considered. We also examine the preference for a secondary structure in bacterial proteins and compare the results to those of human proteins.

  16. Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells.

    Science.gov (United States)

    Lei, Min; Gan, Xianwen; Zhao, Kun; Yu, Qiang; Hu, Lihong

    2015-02-01

    The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity. PMID:25571795

  17. Effect of dimethylaminoethanol and compound amino acid solution on collagen metabolism and free radicals in D-galactose induced aging rat skin%二甲氨基乙醇和复方氨基酸溶液对衰老大鼠皮肤胶原代谢和自由基的影响

    Institute of Scientific and Technical Information of China (English)

    赵彩玲; 匡瑞霞; 刘肃; 闫丙健

    2014-01-01

    Objective To study the mechanism of anti-aging effect of dimethylaminoethanol (DMAE) and compound amino acid (AA) injection by mesotheray in D-galactose-induced skin aging rat.Methods Eighty rats were randomly divided into aging treatment group (60 cases),aging control group (10 cases) and normal control group (10 cases).The skin aging models were established by subcutaneous infectim of D-galactose.From the 18th day,the aging treatment group were injected intradermally in the rats' both sides hip skin with 0.2% DMAE+ AA,0.1% DMAE+AA,0.2%DMAE,0.1% DMAE,AA,and saline,once a week.After four weeks,HE,water content,superoxide dismutase (SOD) activity,hydroxyproline (HYP) and malondialdehyde (MDA) content were measured.Results Compared with the aging control group,the epidermal and the dermal thickness and the collagen area of rats skin' increased significantly in 0.2 % DMAE+ AA and 0.1% DMAE+ AA treatment groups (P<0.05).0.2% DMAE+AA and 0.1 % DMAE+AA treatment groups also had higher SOD activity,HYP content and lower MDA content than other groups (P<0.05),but no difference was noted among normal control group,0.2% DMAE+AA and 0.1% DMAE+AA group (P>0.05).There were no differences in water content among groups (P>0.05).Conclusions Intradermal injection with 0.1% DMAE+ AA and 0.2 % DMAE+AA in aging rats may increase the epidermal and the dermal thickness and the collagen of rats skin' improve SOD activity,HYP content and decreased MDA content,indicating that it has ability to clear skin free radicals,enhance antioxidant capacity and skin collagen metabolism,and thus prevent skin aging.%目的 探讨真皮内注射二甲氨基乙醇(DMAE)和复方氨基酸溶液(AA)对皮肤胶原代谢和自由基的影响.方法 80只大鼠随机分成衰老治疗组(60只)、衰老对照组(10只)和正常对照组(10只).皮下注射半乳糖制备衰老模型.衰老治疗组从第18天开始,在两侧臀部真皮内分别注射0.2% DMAE+AA、0.1

  18. 2-Amino-5-chloropyridinium trifluoroacetate

    Directory of Open Access Journals (Sweden)

    Madhukar Hemamalini

    2010-04-01

    Full Text Available The asymmetric unit of the title salt, C5H6ClN2+·C2F3O2−, contains two independent 2-amino-5-chloropyridinium cations and two independent trifluoroacetate anions. The F atoms of both anions are disordered over two sets of positions, with occupancy ratios of 0.672 (12:0.328 (12 and 0.587 (15:0.413 (15. In the crystal, the cations and anions are linked via N—H...O and C—H...O hydrogen bonds, forming a two-dimensional network parallel to (001.

  19. Solitons and ionospheric modification

    Science.gov (United States)

    Sheerin, J. P.; Nicholson, D. R.; Payne, G. L.; Hansen, P. J.; Weatherall, J. C.; Goldman, M. V.

    1982-01-01

    The possibility of Langmuir soliton formation and collapse during ionospheric modification is investigated. Parameters characterizing former facilities, existing facilities, and planned facilities are considered, using a combination of analytical and numerical techniques. At a spatial location corresponding to the exact classical reflection point of the modifier wave, the Langmuir wave evolution is found to be dominated by modulational instability followed by soliton formation and three-dimensional collapse. The earth's magnetic field is found to affect the shape of the collapsing soliton. These results provide an alternative explanation for some recent observations.

  20. Enzymatic Modification of Sphingomyelin

    DEFF Research Database (Denmark)

    -efficient, high yield production methods are of great interest. In the present study, the potential of producing ceramide through the enzymatic hydrolysis of sphingomyelin have been studied. sphingomyelin is a ubiquitous membrane-lipid and rich in dairy products or by-products. It has been verified that...... sphingomyelin modification gives a feasible approach to the potential production of ceramide. The reaction system has been improved through system evaluation and the optimization of several important factors, and phospholipase C from Clostridium perfringens shows higher activity towards the hydrolysis reaction...

  1. Novel Insights into the Diversity of Catabolic Metabolism from Ten Haloarchaeal Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Iain; Scheuner, Carmen; Goker, Markus; Mavromatis, Kostas; Hooper, Sean D.; Porat, Iris; Klenk, Hans-Peter; Ivanova, Natalia; Kyrpides, Nikos

    2011-05-03

    The extremely halophilic archaea are present worldwide in saline environments and have important biotechnological applications. Ten complete genomes of haloarchaea are now available, providing an opportunity for comparative analysis. We report here the comparative analysis of five newly sequenced haloarchaeal genomes with five previously published ones. Whole genome trees based on protein sequences provide strong support for deep relationships between the ten organisms. Using a soft clustering approach, we identified 887 protein clusters present in all halophiles. Of these core clusters, 112 are not found in any other archaea and therefore constitute the haloarchaeal signature. Four of the halophiles were isolated from water, and four were isolated from soil or sediment. Although there are few habitat-specific clusters, the soil/sediment halophiles tend to have greater capacity for polysaccharide degradation, siderophore synthesis, and cell wall modification. Halorhabdus utahensis and Haloterrigena turkmenica encode over forty glycosyl hydrolases each, and may be capable of breaking down naturally occurring complex carbohydrates. H. utahensis is specialized for growth on carbohydrates and has few amino acid degradation pathways. It uses the non-oxidative pentose phosphate pathway instead of the oxidative pathway, giving it more flexibility in the metabolism of pentoses. These new genomes expand our understanding of haloarchaeal catabolic pathways, providing a basis for further experimental analysis, especially with regard to carbohydrate metabolism. Halophilic glycosyl hydrolases for use in biofuel production are more likely to be found in halophiles isolated from soil or sediment.

  2. The effects of the formula of amino acids enriched BCAA on nutritional support in traumatic patients

    Institute of Scientific and Technical Information of China (English)

    Xin-Ying Wang; Ning Li; Jun Gu; Wei-Qin Li; Jie-Shou Li

    2003-01-01

    AIM: To investigate the formula of amino acid enriched BCAA on nutritional support in traumatic patients after operation.METHODS: 40 adult patients after moderate or large abdominal operations were enrolled in a prospective,randomly and single-blind-controlled study, and total parenteral nutrition (TPN) with either formula of amino acid (AA group, 20 cases) or formula of amino acid enriched BCAA (BCAA group, 20 cases). From the second day after operation, total parenteral nutrition was infused to the patients in both groups with equal calorie and equal nitrogen by central or peripheral vein during more than 12 hours per day for 6 days. Meanwhile, nitrogen balance was assayed by collecting 24 hours urine for 6 days. The markers of protein metabolism were investigated such as amino acid patterns, levels of total protein, albumin, prealbumin,transferrin and fibronectin in serum.RESULTS: The positive nitrogen balance in BCAA group occurred two days earlier than that in AA group. The serum levels oftotal protein and albumin in BCAA group were increased more obviously than that in AA group. The concentration of valine was notably increased and the concentration of arginine was markedly decreased in BCAA group after the formula of amino acids enriched BCAA transfusion.CONCLUSION: The formula of amino acid enriched BCAA may normalize the levels of serum amino acids, reduce the proteolysis, increase the synthesis of protein, improve the nutritional status of traumatic patients after operation.

  3. Plasma amino acid concentrations in 36 dogs with histologically confirmed superficial necrolytic dermatitis.

    Science.gov (United States)

    Outerbridge, Catherine A; Marks, Stanley L; Rogers, Quinton R

    2002-08-01

    Plasma amino acid concentrations were measured in 36 dogs diagnosed with superficial necrolytic dermatitis (SND) via skin biopsy. The median age of the dogs was 10 years, and 27 out of 36 (75%) were male. Twenty-two out of 36 (61%) of the dogs were accounted for by six breeds; West Highland white terriers (six), Shetland sheepdogs (five), cocker spaniels (four), Scottish terriers (three), Lhasa apsos (two) and Border collies (two). The mean concentration (+/- standard deviation) was calculated for each measured plasma amino acid and compared to previously documented concentrations of plasma amino acids measured in dogs with acute and chronic hepatitis. The ratio of branched chain amino acids to aromatic amino acids in the dogs with SND was 2.6, slightly lower than that in normal dogs. The mean plasma amino acid concentrations for dogs with SND were significantly lower than for dogs with acute and chronic hepatitis. A metabolic hepatopathy in which there is increased hepatic catabolism of amino acids is hypothesized to explain the hypoaminoacidaemia seen in SND. PMID:12174180

  4. Animals are dependent on preformed alpha-amino nitrogen as an essential nutrient.

    Science.gov (United States)

    Katagiri, Masayuki; Nakamura, Masahiko

    2002-02-01

    It has traditionally been thought that animals can utilize ammonia for amino acid biosynthesis, and that for them some amino acids are nutritionally nonessential. Presumably this idea originates from the notions of Schoenheimer (G. L. Foster et al. [1939] J. Biol. Chem. 127, 319-327) and of Rose (W. C. Rose et al. [1948] J. Biol. Chem. 176, 753-762), which we question for the following reasons. First, Schoenheimer's experiments only showed the incorporation of ammonia into amino acids. This may occur simply as an exchange between ammonia and the alpha-amino group of endogenous amino acids and reflects the enzymatic properties of glutamate dehydrogenase, which is a reversible enzyme. Second, Rose's nutritional experiments were concerned with whether carbon skeletons of particular amino acids can (nonessential) or cannot (essential) be synthesized from common intermediates of carbohydrate metabolism. We propose that mammals, living as they do at the top of the food web, are absolutely dependent directly or indirectly on higher plants and microorganisms for preformed alpha-amino nitrogen per se and that the first joining of C- and N-atoms to make glutamate constitutes a basic anabolic system in nature after the fixation of CO2 and N2. PMID:12049195

  5. Evaluation of the protein metabolism during hepatic coma evidenced by 15N tracer data

    International Nuclear Information System (INIS)

    In patients in coma hepaticum as well as in pigs with experimental hepatic coma the protein metabolism was studied under conditions of parenteral application of an amino acid diet using 15N-glycine as tracer

  6. Stable isotope studies reveal pathways for the incorporation of non-essential amino acids in Acyrthosiphon pisum (pea aphids).

    Science.gov (United States)

    Haribal, Meena; Jander, Georg

    2015-12-01

    Plant roots incorporate inorganic nitrogen into the amino acids glutamine, glutamic acid, asparagine and aspartic acid, which together serve as the primary metabolites of nitrogen transport to other tissues. Given the preponderance of these four amino acids, phloem sap is a nutritionally unbalanced diet for phloem-feeding insects. Therefore, aphids and other phloem feeders typically rely on microbial symbionts for the synthesis of essential amino acids. To investigate the metabolism of the four main transport amino acids by the pea aphid (Acyrthosiphon pisum), and its Buchnera aphidicola endosymbionts, aphids were fed defined diets with stable isotope-labeled glutamine, glutamic acid, asparagine or aspartic acid (U-(13)C, U-(15)N; U-(15)N; α-(15)N; or γ-(15)N). The metabolic fate of the dietary (15)N and (13)C was traced using gas chromatography-mass spectrometry (GC-MS). Nitrogen was the major contributor to the observed amino acid isotopomers with one additional unit mass (M+1). However, there was differential incorporation, with the amine nitrogen of asparagine being incorporated into other amino acids more efficiently than the amide nitrogen. Higher isotopomers (M+2, M+3 and M+4) indicated the incorporation of varying numbers of (13)C atoms into essential amino acids. GC-MS assays also showed that, even with an excess of dietary labeled glutamine, glutamic acid, asparagine or aspartic acid, the overall content of these amino acids in aphid bodies was mostly the product of catabolism of dietary amino acids and subsequent re-synthesis within the aphids. Thus, these predominant dietary amino acids are not passed directly to Buchnera endosymbionts for synthesis of essential amino acids, but are rather are produced de novo, most likely by endogenous aphid enzymes. PMID:26632455

  7. Posttranslational Modifications and the Immunogenicity of Biotherapeutics

    Directory of Open Access Journals (Sweden)

    Roy Jefferis

    2016-01-01

    Full Text Available Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs, including quality control (QC in the endoplasmic reticulum (ER and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA; aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs, a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.

  8. Perspectives for a better understanding of the metabolic integration of photorespiration within a complex plant primary metabolism network.

    Science.gov (United States)

    Hodges, Michael; Dellero, Younès; Keech, Olivier; Betti, Marco; Raghavendra, Agepati S; Sage, Rowan; Zhu, Xin-Guang; Allen, Doug K; Weber, Andreas P M

    2016-05-01

    Photorespiration is an essential high flux metabolic pathway that is found in all oxygen-producing photosynthetic organisms. It is often viewed as a closed metabolic repair pathway that serves to detoxify 2-phosphoglycolic acid and to recycle carbon to fuel the Calvin-Benson cycle. However, this view is too simplistic since the photorespiratory cycle is known to interact with several primary metabolic pathways, including photosynthesis, nitrate assimilation, amino acid metabolism, C1 metabolism and the Krebs (TCA) cycle. Here we will review recent advances in photorespiration research and discuss future priorities to better understand (i) the metabolic integration of the photorespiratory cycle within the complex network of plant primary metabolism and (ii) the importance of photorespiration in response to abiotic and biotic stresses. PMID:27053720

  9. A metabolic signature of long life in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Viney Jonathan M

    2010-02-01

    Full Text Available Abstract Background Many Caenorhabditis elegans mutations increase longevity and much evidence suggests that they do so at least partly via changes in metabolism. However, up until now there has been no systematic investigation of how the metabolic networks of long-lived mutants differ from those of normal worms. Metabolomic technologies, that permit the analysis of many untargeted metabolites in parallel, now make this possible. Here we use one of these, 1H nuclear magnetic resonance spectroscopy, to investigate what makes long-lived worms metabolically distinctive. Results We examined three classes of long-lived worms: dauer larvae, adult Insulin/IGF-1 signalling (IIS-defective mutants, and a translation-defective mutant. Surprisingly, these ostensibly different long-lived worms share a common metabolic signature, dominated by shifts in carbohydrate and amino acid metabolism. In addition the dauer larvae, uniquely, had elevated levels of modified amino acids (hydroxyproline and phosphoserine. We interrogated existing gene expression data in order to integrate functional (metabolite-level changes with transcriptional changes at a pathway level. Conclusions The observed metabolic responses could be explained to a large degree by upregulation of gluconeogenesis and the glyoxylate shunt as well as changes in amino acid catabolism. These responses point to new possible mechanisms of longevity assurance in worms. The metabolic changes observed in dauer larvae can be explained by the existence of high levels of autophagy leading to recycling of cellular components. See associated minireview: http://jbiol.com/content/9/1/7

  10. 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

    2016-01-01

    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. PMID:26398285

  11. Correlation between fibroin amino acid sequence and physical silk properties.

    Science.gov (United States)

    Fedic, Robert; Zurovec, Michal; Sehnal, Frantisek

    2003-09-12

    The fiber properties of lepidopteran silk depend on the amino acid repeats that interact during H-fibroin polymerization. The aim of our research was to relate repeat composition to insect biology and fiber strength. Representative regions of the H-fibroin genes were sequenced and analyzed in three pyralid species: wax moth (Galleria mellonella), European flour moth (Ephestia kuehniella), and Indian meal moth (Plodia interpunctella). The amino acid repeats are species-specific, evidently a diversification of an ancestral region of 43 residues, and include three types of regularly dispersed motifs: modifications of GSSAASAA sequence, stretches of tripeptides GXZ where X and Z represent bulky residues, and sequences similar to PVIVIEE. No concatenations of GX dipeptide or alanine, which are typical for Bombyx silkworms and Antheraea silk moths, respectively, were found. Despite different repeat structure, the silks of G. mellonella and E. kuehniella exhibit similar tensile strength as the Bombyx and Antheraea silks. We suggest that in these latter two species, variations in the repeat length obstruct repeat alignment, but sufficiently long stretches of iterated residues get superposed to interact. In the pyralid H-fibroins, interactions of the widely separated and diverse motifs depend on the precision of repeat matching; silk is strong in G. mellonella and E. kuehniella, with 2-3 types of long homogeneous repeats, and nearly 10 times weaker in P. interpunctella, with seven types of shorter erratic repeats. The high proportion of large amino acids in the H-fibroin of pyralids has probably evolved in connection with the spinning habit of caterpillars that live in protective silk tubes and spin continuously, enlarging the tubes on one end and partly devouring the other one. The silk serves as a depot of energetically rich and essential amino acids that may be scarce in the diet. PMID:12816957

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

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Rogero

    2008-12-01

    modulation of the immune response, in performance enhancement of individuals who work out in hot environments, and in avoiding muscle lesion. This review approaches all aspects of the metabolism of and supplementation with branched chain amino acids in physical exercise.

  13. Lifestyle modification and endothelial function in obese subjects.

    Science.gov (United States)

    Hamdy, Osama

    2005-03-01

    The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with

  14. Relative Quantification of Sites of Peptide and Protein Modification Using Size Exclusion Chromatography Coupled with Electron Transfer Dissociation

    Science.gov (United States)

    Xie, Boer; Sharp, Joshua S.

    2016-08-01

    One difficult problem in the analysis of peptide modifications is quantifying isomeric modifications that differ by the position of the amino acid modified. HPLC separation using C18 reverse phase chromatography coupled with electron transfer dissociation (ETD) in tandem mass spectrometry has recently been shown to be able to relatively quantify how much of a given modification occurs at each amino acid position for isomeric mixtures; however, the resolution of reverse phase chromatography greatly complicates quantification of isomeric modifications by ETD because of the chromatographic separation of peptides with identical modifications at different sequence positions. Using peptide oxidation as a model system, we investigated the use of size exclusion chromatography coupled with ETD fragmentation to separate peptide sequences. This approach allows for the benefits of chromatographic separation of peptide sequences while ensuring co-elution of modification isomers for accurate relative quantification of modifications using standard data-dependent acquisitions. Using this method, the relative amount of modification at each amino acid can be accurately measured from single ETD MS/MS spectra in a standard data-dependent acquisition experiment.

  15. Relative Quantification of Sites of Peptide and Protein Modification Using Size Exclusion Chromatography Coupled with Electron Transfer Dissociation.

    Science.gov (United States)

    Xie, Boer; Sharp, Joshua S

    2016-08-01

    One difficult problem in the analysis of peptide modifications is quantifying isomeric modifications that differ by the position of the amino acid modified. HPLC separation using C18 reverse phase chromatography coupled with electron transfer dissociation (ETD) in tandem mass spectrometry has recently been shown to be able to relatively quantify how much of a given modification occurs at each amino acid position for isomeric mixtures; however, the resolution of reverse phase chromatography greatly complicates quantification of isomeric modifications by ETD because of the chromatographic separation of peptides with identical modifications at different sequence positions. Using peptide oxidation as a model system, we investigated the use of size exclusion chromatography coupled with ETD fragmentation to separate peptide sequences. This approach allows for the benefits of chromatographic separation of peptide sequences while ensuring co-elution of modification isomers for accurate relative quantification of modifications using standard data-dependent acquisitions. Using this method, the relative amount of modification at each amino acid can be accurately measured from single ETD MS/MS spectra in a standard data-dependent acquisition experiment. Graphical Abstract ᅟ. PMID:27075875

  16. Degradation of fructans and production of propionic acid by Bacteroides thetaiotaomicron are enhanced by shortage of amino acids

    Directory of Open Access Journals (Sweden)

    Signe eAdamberg

    2014-12-01

    Full Text Available Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by the catabolism of various polysaccharides. A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. The polyfructans inulin (from chicory and levan (synthesized using levansucrase from Pseudomonas syringae, two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. The calorimetric power-time curves were substrate specific and typically multiauxic. A surplus of amino acids reduced the consumption of longer oligosaccharides (DP > 3. Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h, followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. In the medium supplemented with 20 amino acids, the highest production of D-lactate (82 ± 33 mmol/gDW occurred in parallel with extensive consumption (up to 17 mmol/gDW of amino acids, especially Ser, Thr and Asp. The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. The effect of levan on balancing or modifying colon microbiota will be studied in

  17. Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids.

    Science.gov (United States)

    Adamberg, Signe; Tomson, Katrin; Vija, Heiki; Puurand, Marju; Kabanova, Natalja; Visnapuu, Triinu; Jõgi, Eerik; Alamäe, Tiina; Adamberg, Kaarel

    2014-01-01

    Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. The calorimetric power-time curves were substrate specific and typically multiauxic. A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. The effect of levan on balancing or modifying colon microbiota will

  18. Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort 1 2

    OpenAIRE

    Schmidt, Julie A; Rinaldi, Sabina; Ferrari, Pietro; Carayol, Marion; Achaintre, David; Scalbert, Augustin; Cross, Amanda J; Gunter, Marc J.; Fensom, Georgina K; Appleby, Paul N.; Key, Timothy J; Travis, Ruth C.

    2015-01-01

    Background: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. Objective: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism betw...

  19. Proline metabolism and transport in plant development

    OpenAIRE

    Lehmann, Silke; Funck, Dietmar; Szabados, László; Rentsch, Doris

    2010-01-01

    Proline fulfils diverse functions in plants. As amino acid it is a structural component of proteins, but it also plays a role as compatible solute under environmental stress conditions. Proline metabolism involves several subcellular compartments and contributes to the redox balance of the cell. Proline synthesis has been associated with tissues undergoing rapid cell divisions, such as shoot apical meristems, and appears to be involved in floral transition and embryo development. High levels ...

  20. Exercise and Amino Acid Anabolic Cell Signaling and the Regulation of Skeletal Muscle Mass

    Directory of Open Access Journals (Sweden)

    Stefan M. Pasiakos

    2012-07-01

    Full Text Available A series of complex intracellular networks influence the regulation of skeletal muscle protein turnover. In recent years, studies have examined how cellular regulators of muscle protein turnover modulate metabolic mechanisms contributing to the loss, gain, or conservation of skeletal muscle mass. Exercise and amino acids both stimulate anabolic signaling potentially through several intracellular pathways including the mammalian target of rapamycin complex 1 and the mitogen activated protein kinase cell signaling cascades. As novel molecular regulators of muscle integrity continue to be explored, a contemporary analysis of the literature is required to understand the metabolic mechanisms by which contractile forces and amino acids affect cellular process that contribute to long-term adaptations and preservation of muscle mass. This article reviews the literature related to how exercise and amino acid availability affect cellular regulators of skeletal muscle mass, especially highlighting recent investigations that have identified mechanisms by which contractile forces and amino acids modulate muscle health. Furthermore, this review will explore integrated exercise and nutrition strategies that promote the maintenance of muscle health by optimizing exercise, and amino acid-induced cell signaling in aging adults susceptible to muscle loss.

  1. Separation and detection of amino acid metabolites of Escherichia coli in microbial fuel cell with CE.

    Science.gov (United States)

    Wang, Wei; Ma, Lihong; Lin, Ping; Xu, Kaixuan

    2016-07-01

    In this work, CE-LIF was employed to investigate the amino acid metabolites produced by Escherichia coli (E. coli) in microbial fuel cell (MFC). Two peptides, l-carnosine and l-alanyl-glycine, together with six amino acids, cystine, alanine, lysine, methionine, tyrosine, arginine were separated and detected in advance by a CE-LIF system coupled with a homemade spontaneous injection device. The injection device was devised to alleviate the effect of electrical discrimination for analytes during sample injection. All analytes could be completely separated within 8 min with detection limits of 20-300 nmol/L. Then this method was applied to analyze the substrate solution containing amino acid metabolites produced by E. coli. l-carnosine, l-alanyl-glycine, and cystine were used as the carbon, nitrogen, and sulfur source for the E. coli culture in the MFC to investigate the amino acid metabolites during metabolism. Two MFCs were used to compare the activity of metabolism of the bacteria. In the sample collected at the running time 200 h of MFC, the amino acid methionine was discovered as the metabolite with the concentrations 23.3 μg/L. PMID:27121957

  2. Optimizing sample pretreatment for compound-specific stable carbon isotopic analysis of amino sugars in marine sediment

    Directory of Open Access Journals (Sweden)

    R. Zhu

    2014-01-01

    Full Text Available Amino sugars are quantitatively significant constituents of soil and marine sediment, but their sources and turnover in environmental samples remain poorly understood. The stable carbon isotopic composition of amino sugars can provide information on the lifestyles of their source organisms and can be monitored during incubations with labeled substrates to estimate the turnover rates of microbial populations. However, until now, such investigation has been carried out only with soil samples, partly because of the much lower abundance of amino sugars in marine environments. We therefore optimized a procedure for compound-specific isotopic analysis of amino sugars in marine sediment employing gas chromatography-isotope ratio mass spectrometry. The whole procedure consisted of hydrolysis, neutralization, enrichment, and derivatization of amino sugars. Except for the derivatization step, the protocol introduced negligible isotopic fractionation, and the minimum requirement of amino sugar for isotopic analysis was 20 ng, i.e. equivalent to ~ 8 ng of amino sugar carbon. Our results obtained from δ13C analysis of amino sugars in selected marine sediment samples showed that muramic acid had isotopic imprints from indigenous bacterial activities, whereas glucosamine and galactosamine were mainly derived from organic detritus. The analysis of stable carbon isotopic compositions of amino sugars opens a promising window for the investigation of microbial metabolisms in marine sediments and the deep marine biosphere.

  3. Optimizing sample pretreatment for compound-specific stable carbon isotopic analysis of amino sugars in marine sediment

    Science.gov (United States)

    Zhu, R.; Lin, Y.-S.; Lipp, J. S.; Meador, T. B.; Hinrichs, K.-U.

    2014-09-01

    Amino sugars are quantitatively significant constituents of soil and marine sediment, but their sources and turnover in environmental samples remain poorly understood. The stable carbon isotopic composition of amino sugars can provide information on the lifestyles of their source organisms and can be monitored during incubations with labeled substrates to estimate the turnover rates of microbial populations. However, until now, such investigation has been carried out only with soil samples, partly because of the much lower abundance of amino sugars in marine environments. We therefore optimized a procedure for compound-specific isotopic analysis of amino sugars in marine sediment, employing gas chromatography-isotope ratio mass spectrometry. The whole procedure consisted of hydrolysis, neutralization, enrichment, and derivatization of amino sugars. Except for the derivatization step, the protocol introduced negligible isotopic fractionation, and the minimum requirement of amino sugar for isotopic analysis was 20 ng, i.e., equivalent to ~8 ng of amino sugar carbon. Compound-specific stable carbon isotopic analysis of amino sugars obtained from marine sediment extracts indicated that glucosamine and galactosamine were mainly derived from organic detritus, whereas muramic acid showed isotopic imprints from indigenous bacterial activities. The δ13C analysis of amino sugars provides a valuable addition to the biomarker-based characterization of microbial metabolism in the deep marine biosphere, which so far has been lipid oriented and biased towards the detection of archaeal signals.

  4. RNA modifications by oxidation

    DEFF Research Database (Denmark)

    Poulsen, Henrik E; Specht, Elisabeth; Broedbaek, Kasper;

    2012-01-01

    to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation......, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas...... other RNA molecules show virtually no oxidation. The iron-storage disease hemochromatosis exhibits the most prominent general increase in RNA oxidation ever observed. Oxidation of RNA primarily leads to strand breaks and to oxidative base modifications. Oxidized mRNA is recognized by the ribosomes...

  5. Radiation Modification of Textiles

    International Nuclear Information System (INIS)

    The application of ionizing radiation to textile finishing operations has become a commercial reality. Electron accelerators are currently being used in a process which imparts durable press, stain-releasing properties to a polyester-cotton blend fabric (Deering-Milliken Co., USA). There are other textile and chemical companies which have announced laboratory or pilot plant development of radiation-textile finishing processes. During the past ten years there has also been a tremendous number of research publications on radiation initiated reactions in fibres or fibre-monomer systems. This paper first briefly reviews the principles of radiation modification of textiles. The important molecular factors controlling such processes and their interaction will be considered. These factors include the G-values for radical formation, local propagation, transfer and termination rate constants, local monomer concentration and its coefficient of diffusion within the polymer matrix, radiation dose rate, temperature, and the presence of non-reactive (e.g. solvent) species. Economic factors will also be considered. Following this there is a review;of the most pertinent recent published work in this field, including the patent literature. This survey will be broken into two parts: bulk effects and surface effects. Emphasis will be placed on durable press and stain release properties. The chemistry of durable press and its application within the field of radiation chemistry will be covered. The principles of surface chemistry will then be discussed, as they relate to important wetting phenomena in textile fibres and fabrics. Data will be presented from a series of studies which the author has been conducting on the radiation modification of surface wettability of textile materials. (author)

  6. Amino Acids as a Source of Organic Nitrogen in Antarctic Endolithic Microbial Communities

    Science.gov (United States)

    McDonald, G. D.; Sun, H. J.

    2002-12-01

    In the Antarctic Dry Valleys, cryptoendolithic microbial communities occur within porous sandstone rocks. Current understanding of the mechanisms of physiological adaptation of these communities to the harsh Antarctic environment is limited, because traditional methods of studying microbial physiology are very difficult to apply to organisms with extremely low levels of metabolic activity. In order to fully understand carbon and nitrogen cycling and nutrient uptake in cryptoendolithic communities, and the metabolic costs that the organisms incur in order to survive, it is necessary to employ molecular geochemical techniques such as amino acid analysis in addition to physiological methods. Low-molecular-weight biomolecules such as amino acids can be used as tracers of carbon and nitrogen uptake and loss by microbial communities living in solid-state matrices such as rock or sediment. We have measured the concentrations and D/L ratios for several amino acids as a function of depth in a large sandstone boulder. Concentrations of both free and bound amino acids decrease by more than two orders of magnitude from the surface to the visible base of the community (approximately 1.2 cm depth), while the D/L ratios of the amino acids increase from near zero to 0.2 or greater over the same depth interval. We interpret these data as an indication that one or more community members are selectively scavenging L-amino acids as the amino acids are transported through the rock by intermittently percolating meltwater. This is consistent with the known preference of lichens for amino acids as nitrogen sources rather than inorganic nitrogen under conditions of nutrient limitation. It is not yet clear whether there is also a contribution to amino acid uptake from heterotropic bacteria associated with the cryptoendolithic community. The increase in D/L ratios with depth observed in the rock is too great to be attributable solely to the natural occurrence of D-amino acids in bacteria

  7. Amino acids in the Tagish Lake Meteorite

    Science.gov (United States)

    Kminek, G.; Botta, O.; Glavin, D. P.; Bada, J. L.

    2002-01-01

    High-performance liquid chromatography (HPLC) based amino acid analysis of a Tagish Lake meteorite sample recovered 3 months after the meteorite fell to Earth have revealed that the amino acid composition of Tagish Lake is strikingly different from that of the CM and CI carbonaceous chondrites. We found that the Tagish Lake meteorite contains only trace levels of amino acids (total abundance = 880 ppb), which is much lower than the total abundance of amino acids in the CI Orgueil (4100 ppb) and the CM Murchison (16 900 ppb). Because most of the same amino acids found in the Tagish Lake meteorite are also present in the Tagish Lake ice melt water, we conclude that the amino acids detected in the meteorite are terrestrial contamination. We found that the exposure of a sample of Murchison to cold water lead to a substantial reduction over a period of several weeks in the amount of amino acids that are not strongly bound to the meteorite matrix. However, strongly bound amino acids that are extracted by direct HCl hydrolysis are not affected by the leaching process. Thus even if there had been leaching of amino acids from our Tagish Lake meteorite sample during its 3 month residence in Tagish Lake ice and melt water, a Murchison type abundance of endogenous amino acids in the meteorite would have still been readily detectable. The low amino acid content of Tagish Lake indicates that this meteorite originated fiom a different type of parent body than the CM and CI chondrites. The parent body was apparently devoid of the reagents such as aldehyldes/ketones, HCN and ammonia needed for the effective abiotic synthesis of amino acids. Based on reflectance spectral measurements, Tagish Lake has been associated with P- or D-type asteroids. If the Tagish Lake meteorite was indeed derived fiom these types of parent bodies, our understanding of these primitive asteroids needs to be reevaluated with respect to their potential inventory of biologically important organic compounds.

  8. Amino acidis derived from Titan tholins

    Science.gov (United States)

    Khare, Bishun N.; Sagan, Carl; Ogino, Hiroshi; Nagy, Bartholomew; Er, Cevat

    1986-01-01

    The production of amino acids by acid treatment of Titan tholin is experimentally investigated. The synthesis of Titan tholin and the derivatization of amino acids to N-trifluoroacetyl isopropyl esters are described. The gas chromatography/mass spectroscopy analysis of the Titan tholins reveals the presence of glycine, alpha and beta alainine, and aspartic acid, and the total yield of amino acids is about 0.01.

  9. Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease

    Science.gov (United States)

    Kinny-Köster, Benedict; Bartels, Michael; Becker, Susen; Scholz, Markus; Thiery, Joachim

    2016-01-01

    Background The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. Methods 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. Results 33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer’s ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer’s ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. Conclusions Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets. PMID:27410482

  10. Cellular Dynamics of RNA Modification

    Science.gov (United States)

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Conspectus Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characterized protein and DNA modifications, many RNA modifications are not essential for life. Instead, increasingly more evidence indicates that RNA modifications can play regulatory roles in cells, especially in response to stress conditions. In this Account, we review some known examples of RNA modifications that are dynamically controlled in cells and introduce some contemporary technologies and methods that enhance the studies of cellular dynamics of RNA modifications. Examples of RNA modifications discussed in this Account include (Figure 1): (1) 4-thio uridine (s4U) which can act as a cellular sensor of near UV-light; (2) queuosine (Q) which is a potential biomarker for malignancy; (3) N6-methyl adenine (m6A) which is the prevalent modification in eukaryotic mRNAs; and (4) pseudouridine (ψ) which are inducible by nutrient deprivation. Two recent technical advances that stimulated the studies of cellular dynamics of modified ribonucleosides are also described. First, a genome-wide method combines primer extension and microarray to study N1-methyl adenine (m1A) hypomodification in human tRNA. Second, a quantitative mass spectrometric method investigates dynamic changes of a wide range of tRNA modifications under stress conditions in yeast. In addition, we discuss potential mechanisms that control dynamic regulation of RNA modifications, and hypotheses for discovering potential RNA de-modification enzymes. We conclude the Account by highlighting the need to develop new

  11. EPIGENETIC MODIFICATIONS OF SWINE GENOME

    OpenAIRE

    Kristina Budimir; Gordana Kralik; Vladimir Margeta

    2013-01-01

    Epigenetics is represents a new way of genome analysis, respectively gene expression that occurs without DNA sequence change. Changes that occur are epigenetic modifications and they include post-translational histone modification and DNA methylation. Chemical groups that are added on DNA molecule cause changes in DNA and create epigenome. The consequence of that is appearance of imprinted genes in genome. Genetic imprinting is epigenetic modification in which one of inherited alleles inactiv...

  12. Global turnover of histone post-translational modifications and variants in human cells

    Directory of Open Access Journals (Sweden)

    Zee Barry M

    2010-12-01

    Full Text Available Abstract Background Post-translational modifications (PTMs on the N-terminal tails of histones and histone variants regulate distinct transcriptional states and nuclear events. Whereas the functional effects of specific PTMs are the current subject of intense investigation, most studies characterize histone PTMs/variants in a non-temporal fashion and very few studies have reported kinetic information about these histone forms. Previous studies have used radiolabeling, fluorescence microscopy and chromatin immunoprecipitation to determine rates of histone turnover, and have found interesting correlations between increased turnover and increased gene expression. Therefore, histone turnover is an understudied yet potentially important parameter that may contribute to epigenetic regulation. Understanding turnover in the context of histone modifications and sequence variants could provide valuable additional insight into the function of histone replacement. Results In this study, we measured the metabolic rate of labeled isotope incorporation into the histone proteins of HeLa cells by combining stable isotope labeling of amino acids in cell culture (SILAC pulse experiments with quantitative mass spectrometry-based proteomics. In general, we found that most core histones have similar turnover rates, with the exception of the H2A variants, which exhibit a wider range of rates, potentially consistent with their epigenetic function. In addition, acetylated histones have a significantly faster turnover compared with general histone protein and methylated histones, although these rates vary considerably, depending on the site and overall degree of methylation. Histones containing transcriptionally active marks have been consistently found to have faster turnover rates than histones containing silent marks. Interestingly, the presence of both active and silent marks on the same peptide resulted in a slower turnover rate than either mark alone on that same

  13. Indigenous amino acids in primitive CR meteorites

    CERN Document Server

    Martins, Z; Orzechowska, G E; Fogel, M L; Ehrenfreund, P

    2008-01-01

    CR meteorites are among the most primitive meteorites. In this paper, we report the first measurements of amino acids in Antarctic CR meteorites, two of which show the highest amino acid concentrations ever found in a chondrite. EET92042, GRA95229 and GRO95577 were analyzed for their amino acid content using high performance liquid chromatography with UV fluorescence detection (HPLC-FD) and gas chromatographymass spectrometry (GC-MS). Our data show that EET92042 and GRA95229 are the most amino acid-rich chondrites ever analyzed, with total amino acid concentrations ranging from 180 parts-per-million (ppm) to 249 ppm. GRO95577, however, is depleted in amino acids. The most abundant amino acids present in the EET92042 and GRA95229 meteorites are the alpha-amino acids glycine, isovaline, alpha-aminoisobutyric acid (alpha-AIB), and alanine, with delta13C values ranging from +31.6per mil to +50.5per mil. The carbon isotope results together with racemic enantiomeric ratios determined for most amino acids strongly i...

  14. Tissue slices in the study of lung metabolism and toxicology.

    OpenAIRE

    Freeman, B.A.; O'Neil, J. J.

    1984-01-01

    Lung tissue slices are model systems for the study of pulmonary metabolism. Because of the speed and simplicity of slice preparation, lung slices have been used in studies of oxygen, amino acid, carbohydrate and lipid utilization and adenine nucleotide metabolism. Dose-response characteristics for toxicants are readily described because multiple lung samples can be studied from the same animal or a population of animals. Lung slices prepared from animals exposed to oxidant air pollutants exhi...

  15. Corynebacterium glutamicum Metabolic Engineering with CRISPR Interference (CRISPRi)

    OpenAIRE

    Cleto, Sara; Jensen, Jaide VK; Wendisch, Volker F.; Lu, Timothy K.

    2016-01-01

    Corynebacterium glutamicum is an important organism for the industrial production of amino acids. Metabolic pathways in this organism are usually engineered by conventional methods such as homologous recombination, which depends on rare double-crossover events. To facilitate the mapping of gene expression levels to metabolic outputs, we applied CRISPR interference (CRISPRi) technology using deactivated Cas9 (dCas9) to repress genes in C. glutamicum. We then determined the effects of target re...

  16. Relationship between amino acid usage and amino acid evolution in primates.

    Science.gov (United States)

    Liu, Haoxuan; Xie, Zhengqing; Tan, Shengjun; Zhang, Xiaohui; Yang, Sihai

    2015-02-25

    Amino acid usage varies from species to species. A previous study has found a universal trend in amino acid gain and loss in many taxa and a one-way model of amino acid evolution in which the number of new amino acids increases as the number of old amino acids decreases was proposed. Later studies showed that this pattern of amino acid gain and loss is likely to be compatible with the neutral theory. The present work aimed to further study this problem by investigating the evolutionary patterns of amino acids in 8 primates (the nucleotide and protein alignments are available online http://gattaca.nju.edu.cn/pub_data.html). First, the number of amino acids gained and lost was calculated and the evolution trend of each amino acid was inferred. These values were found to be closely related to the usage of each amino acid. Then we analyzed the mutational trend of amino acid substitution in human using SNPs, this trend is highly correlated with fixation trend only with greater variance. Finally, the trends in the evolution of 20 amino acids were evaluated in human on different time scales, and the increasing rate of 5 significantly increasing amino acids was found to decrease as a function of time elapsed since divergence, and the dS/dN ratio also found to increase as a function of time elapsed since divergence. These results suggested that the observed amino acid substitution pattern is influenced by mutation and purifying selection. In conclusion, the present study shows that usage of amino acids is an important factor capable of influencing the observed pattern of amino acid evolution, and also presented evidences suggesting that the observed universal trend of amino acid gain and loss is compatible with neutral evolution. PMID:25527119

  17. The development of orally administrable gemcitabine prodrugs with D-enantiomer amino acids: Enhanced membrane permeability and enzymatic stability

    Science.gov (United States)

    Tsume, Yasuhiro; Incecayir, Tuba; Song, Xueqin; Hilfinger, John M.; Amidon, Gordon L.

    2014-01-01

    Gemcitabine prodrugs with D- and L-configuration amino acids were synthesized and their chemical stability in buffers, resistance to glycosidic bond metabolism, enzymatic activation, permeability in Caco-2 cells and mouse intestinal membrane, anti-proliferation activity in cancer cell were determined and compared to that of parent drug, gemcitabine. Prodrugs containing D-configuration amino acids were enzymatically more stable than ones with L-configuration amino acids. The activation of all gemcitabine prodrugs was 1.3–17.6-fold faster in cancer cell homogenate than their hydrolysis in buffer, suggesting enzymatic action. The enzymatic activation of amino acid monoester prodrugs containing D-configuration amino acids in cell homogenates was 2.2–10.9-fold slower than one of amino acid monoester prodrugs with L-configuration amino acids. All prodrugs exhibited enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase compared to parent gemcitabine. Gemcitabine prodrugs showed superior the effective permeability in mouse jejunum to gemcitabine. More importantly, the high plasma concentration of D-amino acid gemcitabine prodrugs was observed more than one of L-amino acid gem-citabine prodrugs. In general, the 5′-mono-amino acid monoester gemcitabine prodrugs exhibited higher permeability and uptake than their parent drug, gemcitabine. Cell proliferation assays in AsPC-1 pancreatic ductal cell line indicated that gemcitabine prodrugs were more potent than their parent drug, gemcitabine. The transport and enzymatic profiles of 5′-D-valyl-gemcitabine and 5′-D-phenylalanyl-gem-citabine suggest their potential for increased oral uptake and delayed enzymatic bioconversion as well as enhanced uptake and cytotoxic activity in cancer cells, would facilitate the development of oral dosage form for anti-cancer agents and, hence, improve the quality of life for the cancer patients. PMID:24361461

  18. The development of orally administrable gemcitabine prodrugs with D-enantiomer amino acids: enhanced membrane permeability and enzymatic stability.

    Science.gov (United States)

    Tsume, Yasuhiro; Incecayir, Tuba; Song, Xueqin; Hilfinger, John M; Amidon, Gordon L

    2014-04-01

    Gemcitabine prodrugs with D- and L-configuration amino acids were synthesized and their chemical stability in buffers, resistance to glycosidic bond metabolism, enzymatic activation, permeability in Caco-2 cells and mouse intestinal membrane, anti-proliferation activity in cancer cell were determined and compared to that of parent drug, gemcitabine. Prodrugs containing D-configuration amino acids were enzymatically more stable than ones with L-configuration amino acids. The activation of all gemcitabine prodrugs was 1.3-17.6-fold faster in cancer cell homogenate than their hydrolysis in buffer, suggesting enzymatic action. The enzymatic activation of amino acid monoester prodrugs containing D-configuration amino acids in cell homogenates was 2.2-10.9-fold slower than one of amino acid monoester prodrugs with L-configuration amino acids. All prodrugs exhibited enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase compared to parent gemcitabine. Gemcitabine prodrugs showed superior the effective permeability in mouse jejunum to gemcitabine. More importantly, the high plasma concentration of d-amino acid gemcitabine prodrugs was observed more than one of L-amino acid gemcitabine prodrugs. In general, the 5'-mono-amino acid monoester gemcitabine prodrugs exhibited higher permeability and uptake than their parent drug, gemcitabine. Cell proliferation assays in AsPC-1 pancreatic ductal cell line indicated that gemcitabine prodrugs were more potent than their parent drug, gemcitabine. The transport and enzymatic profiles of 5'-D-valyl-gemcitabine and 5'-D-phenylalanyl-gemcitabine suggest their potential for increased oral uptake and delayed enzymatic bioconversion as well as enhanced uptake and cytotoxic activity in cancer cells, would facilitate the development of oral dosage form for anti-cancer agents and, hence, improve the quality of life for the cancer patients. PMID:24361461

  19. Adsorption of 2-picoline and 3-Amino-2-picoline onto kaolin and organo-modified kaolin

    OpenAIRE

    Saeedeh Hashemian; Yalda Parsaei

    2015-01-01

    The adsorption of 2-picoline (PC) and 3-Amino-2-picoline (APC) onto kaolin and organo-modified kaolin was investigated. Tetraethylamoniumiodide (TEAI) was used as modification reagent. The sorbent was characterized by FTIR, XRD, SEM and BET methods. The influence of various parameters like contact time, PH, adsorbent dose and initial concentration of PC and APC was studied. The adsorption kinetics, thermodynamic and isotherms were thoroughly examined. Results show that a pH value of more tha...

  20. Targeted amino-terminal acetylation of recombinant proteins in E. coli.

    Directory of Open Access Journals (Sweden)

    Matthew Johnson

    Full Text Available One major limitation in the expression of eukaryotic proteins in bacteria is an inability to post-translationally modify the expressed protein. Amino-terminal acetylation is one such modification that can be essential for protein function. By co-expressing the fission yeast NatB complex with the target protein in E.coli, we report a simple and widely applicable method for the expression and purification of functional N-terminally acetylated eukaryotic proteins.

  1. A New Achiral Linker Reagent for the Incorporation of Multiple Amino Groups Into Oligonucleotides

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a new functionalized achiral linker reagent for incorporating multiple primary amino groups or reporter groups into oligonucleotides following the phosphoramidite methodology. It is possible to substitute any ribodeoxynucleotide, deoxynucleotide, or nucleotide with...... the linker in conventional phosphoamidite or H-phosphonate DNA syntheses. Directly, or via a post modification step, an oligonucleotide is labelled with one or more reporter moieties, e.g. dansyl (5-dimethylamino)-1-naphthalenesulfonyl), biotin, digoxigenin, DOXYL (N-oxyl-4,4-dimethyloxazolidine...

  2. DNA damage induces phosphorylation of the amino terminus of p53

    OpenAIRE

    Siliciano, Janet D.; Canman, Christine E.; Taya, Yoichi; Sakaguchi, Kazuyasu; Appella, Ettore; Kastan, Michael B.

    1997-01-01

    Data are presented demonstrating that DNA damage leads to specific post-translational modifications of p53 protein. Using two-dimensional peptide mapping of in vivo radiolabeled p53 tryptic phosphopeptides, recombinant truncated p53 protein, and synthetic p53 tryptic peptides, a unique p53 phosphopeptide was identified after exposure of ML-1 cells to ionizing irradiation. This peptide represents the first 24 amino acids of p53 and contains three phosphorylated serine residues. A specific p53 ...

  3. Cell Signalling Through Covalent Modification and Allostery

    Science.gov (United States)

    Johnson, Louise N.

    Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases catalyze the transfer of the γ-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. This covalent modification allows activation or inhibition of enzyme activity, creates recognition sites for other proteins and promotes order/disorder or disorder/order transitions. These properties regulate ­signalling pathways and cellular processes that mediate metabolism, transcription, cell cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. In this lecture I shall review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase and the cell cycle cyclin dependent protein kinases as illustrations. Regulation of protein phosphorylation may be disrupted in the diseased state and protein kinases have become high profile targets for drug development. To date there are 11 compounds that have been approved for clinical use in the treatment of cancer.

  4. Preservation of metabolic activity in lyophilized human erythrocytes.

    OpenAIRE

    Goodrich, R P; Sowemimo-Coker, S O; Zerez, C R; Tanaka, K R

    1992-01-01

    Normal human erythrocytes (RBC) were freeze-dried under conditions that caused minimal modification in normal RBC metabolic activities. Because of the known effects of long-term storage on metabolic activities, we studied the effects of our lyophilization process on RBC metabolism. Of all the metabolic enzymes studied, only triosephosphate isomerase (D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1), enolase (2-phospho-D-glyceratehydro-lyase, EC 4.2.1.11), and pyruvate kinase (ATP:pyr...

  5. High-throughput mass spectrometric discovery of protein post-translational modifications.

    Science.gov (United States)

    Wilkins, M R; Gasteiger, E; Gooley, A A; Herbert, B R; Molloy, M P; Binz, P A; Ou, K; Sanchez, J C; Bairoch, A; Williams, K L; Hochstrasser, D F

    1999-06-11

    The availability of genome sequences, affordable mass spectrometers and high-resolution two-dimensional gels has made possible the identification of hundreds of proteins from many organisms by peptide mass fingerprinting. However, little attention has been paid to how information generated by these means can be utilised for detailed protein characterisation. Here we present an approach for the systematic characterisation of proteins using mass spectrometry and a software tool FindMod. This tool, available on the internet at http://www.expasy.ch/sprot/findmod.html , examines peptide mass fingerprinting data for mass differences between empirical and theoretical peptides. Where mass differences correspond to a post-translational modification, intelligent rules are applied to predict the amino acids in the peptide, if any, that might carry the modification. FindMod rules were constructed by examining 5153 incidences of post-translational modifications documented in the SWISS-PROT database, and for the 22 post-translational modifications currently considered (acetylation, amidation, biotinylation, C-mannosylation, deamidation, flavinylation, farnesylation, formylation, geranyl-geranylation, gamma-carboxyglutamic acids, hydroxylation, lipoylation, methylation, myristoylation, N -acyl diglyceride (tripalmitate), O-GlcNAc, palmitoylation, phosphorylation, pyridoxal phosphate, phospho-pantetheine, pyrrolidone carboxylic acid, sulphation) a total of 29 different rules were made. These consider which amino acids can carry a modification, whether the modification occurs on N-terminal, C-terminal or internal amino acids, and the type of organisms on which the modification can be found. We illustrate the utility of the approach with proteins from 2-D gels of Escherichia coli and sheep wool, where post-translational modifications predicted by FindMod were confirmed by MALDI post-source decay peptide fragmentation. As the approach is amenable to automation, it presents a

  6. Role of histone modifications in defining chromatin structure and function.

    Science.gov (United States)

    Gelato, Kathy A; Fischle, Wolfgang

    2008-04-01

    Chromosomes in eukaryotic cell nuclei are not uniformly organized, but rather contain distinct chromatin elements, with each state having a defined biochemical structure and biological function. These are recognizable by their distinct architectures and molecular components, which can change in response to cellular stimuli or metabolic requirements. Chromatin elements are characterized by the fundamental histone and DNA components, as well as other associated non-histone proteins and factors. Post-translational modifications of histone proteins in particular often correlate with a specific chromatin structure and function. Patterns of histone modifications are implicated as having a role in directing the level of chromatin compaction, as well as playing roles in multiple functional pathways directing the readout of distinct regions of the genome. We review the properties of various chromatin elements and the apparent links of histone modifications with chromatin organization and functional output. PMID:18225984

  7. Amino acid decarboxylations produced by lipid-derived reactive carbonyls in amino acid mixtures.

    Science.gov (United States)

    Hidalgo, Francisco J; León, M Mercedes; Zamora, Rosario

    2016-10-15

    The formation of 2-phenylethylamine and phenylacetaldehyde in mixtures of phenylalanine, a lipid oxidation product, and a second amino acid was studied to determine the role of the second amino acid in the degradation of phenylalanine produced by lipid-derived reactive carbonyls. The presence of the second amino acid usually increased the formation of the amine and reduced the formation of the Strecker aldehyde. The reasons for this behaviour seem to be related to the α-amino group and the other functional groups (mainly amino or similar groups) present in the side-chain of the amino acid. These groups are suggested to modify the lipid-derived reactive carbonyl but not the reaction mechanism because the Ea of formation of both 2-phenylethylamine and phenylacetaldehyde remained unchanged in all studied systems. All these results suggest that the amine/aldehyde ratio obtained by amino acid degradation can be modified by adding free amino acids during food formulation. PMID:27173560

  8. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  9. Copper-Catalyzed Amino Lactonization and Amino Oxygenation of Alkenes Using O-Benzoylhydroxylamines.

    Science.gov (United States)

    Hemric, Brett N; Shen, Kun; Wang, Qiu

    2016-05-11

    A copper-catalyzed amino lactonization of unsaturated carboxylic acids has been achieved as well as the analogous intermolecular three-component amino oxygenation of olefins. The transformation features mild conditions and a remarkably broad substrate scope, offering a novel and efficient approach to construct a wide range of amino lactones as well as 1,2-amino alcohol derivatives. Mechanistic studies suggest that the reaction proceeds via a distinctive O-benzoylhydroxylamine-promoted electrophilic amination of alkenes. PMID:27114046

  10. A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks.

    Science.gov (United States)

    Schuster, S; Fell, D A; Dandekar, T

    2000-03-01

    A set of linear pathways often does not capture the full range of behaviors of a metabolic network. The concept of 'elementary flux modes' provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes. We have used this concept to analyze the interplay between the pentose phosphate pathway (PPP) and glycolysis. The set of elementary modes for this system involves conventional glycolysis, a futile cycle, all the modes of PPP function described in biochemistry textbooks, and additional modes that are a priori equally entitled to pathway status. Applications include maximizing product yield in amino acid and antibiotic synthesis, reconstruction and consistency checks of metabolism from genome data, analysis of enzyme deficiencies, and drug target identification in metabolic networks. PMID:10700151

  11. Amino Acid Compositions of 27 Food Fishes and Their Importance in Clinical Nutrition

    Directory of Open Access Journals (Sweden)

    Bimal Mohanty

    2014-01-01

    Full Text Available Proteins and amino acids are important biomolecules which regulate key metabolic pathways and serve as precursors for synthesis of biologically important substances; moreover, amino acids are building blocks of proteins. Fish is an important dietary source of quality animal proteins and amino acids and play important role in human nutrition. In the present investigation, crude protein content and amino acid compositions of important food fishes from different habitats have been studied. Crude protein content was determined by Kjeldahl method and amino acid composition was analyzed by high performance liquid chromatography and information on 27 food fishes was generated. The analysis showed that the cold water species are rich in lysine and aspartic acid, marine fishes in leucine, small indigenous fishes in histidine, and the carps and catfishes in glutamic acid and glycine. The enriched nutrition knowledge base would enhance the utility of fish as a source of quality animal proteins and amino acids and aid in their inclusion in dietary counseling and patient guidance for specific nutritional needs.

  12. Diauxic growth of Geotrichum candidum and Penicillium camembertii on amino acids and glucose

    Directory of Open Access Journals (Sweden)

    M. Aziza

    2012-06-01

    Full Text Available The purpose of this work was to examine physiological differences between the yeast Geotrichum candidum and the mould Penicillium camembertii, organisms involved in the industrial process of cheese ripening. Three groups of amino acids had previously been characterized, based on their carbon assimilation and dissimilation by the two fungal species. For both of them, a diauxic growth phase had been shown for a group of amino acids, which however had not been examined in light of physiological differences between the two microorganisms. In this work, the higher level of enzymatic activities of P. camembertii if compared to G. candidum was confirmed since a continuous and sequential use of both carbon substrates, glucose and arginine, was recorded during P. camembertii culture; while after glucose depletion, a clear stationary phase was recorded before the assimilation of the considered amino acid as both carbon and nitrogen sources by G. candidum. This behaviour was confirmed for the three amino acids tested, i.e., arginine, proline and glutamic acid. Contrarily, during the two growth phases, on glucose and the test amino acid, respectively, higher growth rates were recorded for G. candidum compared to P. camembertii, showing higher substrate utilisation efficiency by G. candidum. Improving the knowledge regarding the metabolization of amino acids might be helpful in designing strategies aiming at improving processes such as cheese ripening. The work should be followed up by similar works using small peptides.

  13. Dietary requirements of synthesizable amino acids by animals: a paradigm shift in protein nutrition.

    Science.gov (United States)

    Wu, Guoyao

    2014-01-01

    Amino acids are building blocks for proteins in all animals. Based on growth or nitrogen balance, amino acids were traditionally classified as nutritionally essential or nonessential for mammals, birds and fish. It was assumed that all the "nutritionally nonessential amino acids (NEAA)" were synthesized sufficiently in the body to meet the needs for maximal growth and optimal health. However, careful analysis of the scientific literature reveals that over the past century there has not been compelling experimental evidence to support this assumption. NEAA (e.g., glutamine, glutamate, proline, glycine and arginine) play important roles in regulating gene expression, cell signaling, antioxidative responses, fertility, neurotransmission, and immunity. Additionally, glutamate, glutamine and aspartate are major metabolic fuels for the small intestine to maintain its digestive function and to protect the integrity of the intestinal mucosa. Thus, diets for animals must contain all NEAA to optimize their survival, growth, development, reproduction, and health. Furthermore, NEAA should be taken into consideration in revising the "ideal protein" concept that is currently used to formulate swine and poultry diets. Adequate provision of all amino acids (including NEAA) in diets enhances the efficiency of animal production. In this regard, amino acids should not be classified as nutritionally essential or nonessential in animal or human nutrition. The new Texas A&M University's optimal ratios of dietary amino acids for swine and chickens are expected to beneficially reduce dietary protein content and improve the efficiency of their nutrient utilization, growth, and production performance. PMID:24999386

  14. Synthesis of library from amino-hydroxy substituted cyclopentanes

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Lundt, Inge; Andrews, Robert

    Based on radical induced carbocyclisation of unsaturated aldonolactones our group has elaborated procedures for the preparation of several amino-hydroxy substituted cyclopentane derivatives [1]. These highly functionalized molecules are suitable for attachment to solid phase and subsequent parallel...... easily be anchored to PS-resin through the hydroxyl functionalities, forming acetals stable to the subsequent reaction conditions. Then several methods for modification of the amine functionality were investigated, such as reductive amination, sulfonylation and Ugi-reactions. Especially the Ugi......-reaction followed by an opening of the lactone with an amine posed to be a suitable protocol for diversification (fig 2). Figure 2 Reactions performed on solid phase In this way several compounds were synthesized by parallel synthesis and cleaved off the resin. TransTech Pharma has tested these compounds in...

  15. β-Puromycin selection of modified ribosomes for in vitro incorporation of β-amino acids.

    Science.gov (United States)

    Dedkova, Larisa M; Fahmi, Nour Eddine; Paul, Rakesh; del Rosario, Melissa; Zhang, Liqiang; Chen, Shengxi; Feder, Glen; Hecht, Sidney M

    2012-01-10

    Ribosomally mediated protein biosynthesis is limited to α-L-amino acids. A strong bias against β-L-amino acids precludes their incorporation into proteins in vivo and also in vitro in the presence of misacylated β-aminoacyl-tRNAs. Nonetheless, earlier studies provide some evidence that analogues of aminoacyl-tRNAs bearing β-amino acids can be accommodated in the ribosomal A-site. Both functional and X-ray crystallographic data make it clear that the exclusion of β-L-amino acids as participants in protein synthesis is a consequence of the architecture of the ribosomal peptidyltransferase center (PTC). To enable the reorganization of ribosomal PTC architecture through mutagenesis of 23S rRNA, a library of modified ribosomes having modifications in two regions of the 23S rRNA (2057-2063 and 2496-2507 or 2582-2588) was prepared. A dual selection procedure was used to obtain a set of modified ribosomes able to carry out protein synthesis in the presence β-L-amino acids and to provide evidence for the utilization of such amino acids, in addition to α-L-amino acids. β-Puromycin, a putative mimetic for β-aminoacyl-tRNAs, was used to select modified ribosome variants having altered PTC architectures, thus potentially enabling incorporation of β-L-amino acids. Eight types of modified ribosomes altered within the PTC have been selected by monitoring improved sensitivity to β-puromycin in vivo. Two of the modified ribosomes, having 2057AGCGUGA2063 and 2502UGGCAG2507 or 2502AGCCAG2507, were able to suppress UAG codons in E. coli dihydrofolate reductase (DHFR) and scorpion Opisthorcanthus madagascariensis peptide IsCT mRNAs in the presence of β-alanyl-tRNA(CUA). PMID:22145951

  16. Molecular Basis of Prodrug Activation by Human Valacyclovirase, an [alpha]-Amino Acid Ester Hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Longsheng; Xu, Zhaohui; Zhou, Jiahai; Lee, Kyung-Dall; Amidon, Gordon L. (Michigan)

    2008-07-08

    Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of {alpha}-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific {alpha}-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.

  17. Surface Modification of Intraocular Lenses

    Institute of Scientific and Technical Information of China (English)

    Qi Huang; George Pak-Man Cheng; Kin Chiu; Gui-Qin Wang

    2016-01-01

    Objective:This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs).Data Sources:All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect.Study Selection:The articles on the surface modification of IOLs were included,but those on design modification and surface coating were excluded.Results:Technology of surface modification included plasma,ion beam,layer-by-layer self-assembly,ultraviolet radiation,and ozone.The main molecules introduced into IOLs surface were poly (ethylene glycol),polyhedral oligomeric silsesquioxane,2-methacryloyloxyethyl phosphorylcholine,TiO2,heparin,F-heparin,titanium,titanium nitride,vinyl pyrrolidone,and inhibitors of cytokines.The surface modification either resulted in a more hydrophobic lens,a more hydrophilic lens,or a lens with a hydrophilic anterior and hydrophobic posterior surface.Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments.Conclusion:The surface modification is an efficient,convenient,economic and promising method to improve the biocompatibility ofIOLs.

  18. Surface Modification of Intraocular Lenses

    Directory of Open Access Journals (Sweden)

    Qi Huang

    2016-01-01

    Full Text Available Objective: This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs. Data Sources: All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. Study Selection: The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded. Results: Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol, polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments. Conclusion: The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.

  19. Blueberries and Metabolic Syndrome

    Science.gov (United States)

    Metabolic Syndrome is a cluster of metabolic disorders that increase the risk of cardiovascular diseases. Type 2 diabetes, elevated blood pressure, and atherogenic dyslipidemia are among the metabolic alterations that predispose the individual to several adverse cardiovascular complications. The hea...

  20. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... in your body tissues. If you have a metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose ( ...