Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle proteins turn over slowly and there are minimal diurnal changes in the size of the muscle protein pool in response to feeding and fasting. Nitrogen balance and tracer studies indicate that protein oxidation and net protein breakdown (degradation--synthesis) is not increased during dynamic exercise at intensities of < or = 70% VO2max. An imbalance between muscle protein synthesis and degradation does exist during one leg knee extensor exercise and during two legged cycling in patients with glycogen phosphorylase deficiency. In these latter cases amino acids liberated from the protein pool are used for synthesis of TCA-cycle intermediates and glutamine. Six amino acids are metabolized in resting muscle: leucine, isoleucine, valine, asparagine, aspartate and glutamate. Only leucine and part of the isoleucine molecule can be converted to acetylCoA and oxidized. The carbon skeleton of the other amino acids is used for synthesis of TCA-cycle intermediates and glutamine. The six amino acids provide the amino groups and the ammonia for synthesis of glutamine and alanine, which are released by muscle in excessive amounts. About half of the glutamine release from muscle originates from glutamate taken up from the blood. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates and a high TCA cycle flux in the first minutes of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen depleted muscles and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen depleted muscles but only allow exercise at 40-50% of Wmax. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen depleted muscles due to insufficient TCA-cycle anaplerosis and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle thus seem to play a central role in the energy metabolism of the exercising muscle.
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PMID:Protein and amino acid metabolism in human muscle. 978 36

Chronic occupational exposure to organophosphorus and carbamate-type pesticides significantly inhibits acetylcholinesterase activity and causes morbidity. This study on mice was designed to evaluate their amino profile and to identify signs of hepatic dysfunction following their chronic exposure to mixtures of organophosphorus pesticides. Laboratory mice were exposed to a formulated mixture of the six organophosphorus pesticides (Dimethoate, Chlorpyrifos, Profenofos, Pirimiphos methyl, Triazophos and Dimethoate) most commonly used in agriculture in this region of the Middle East. Doses (10% of LD50 of the mixture) were given once a week by gavage in corn oil for 7 weeks; the control group was given only corn oil. At the end of the exposure period, mice were culled and blood samples were collected to determine erythrocyte acetylcholinesterase activity, biochemical markers of liver function and concentrations of serum amino acids. Erythrocyte acetylcholinesterase activity and total serum proteins decreased significantly in the exposed group. Serum concentrations of alanine aminotransferase and aspartate aminotransferase, alanine, glutamic acid, glycine, isoleucine, leucine, methionine, ornithine, proline, serine, threonine and valine were significantly increased in the exposed mice, while serum levels of cystine were decreased significantly. There were also non-significant increases in serum alkaline phosphatase, gama-glutamyl transpeptidase and some of the other amino acids. Chronic exposure to mixtures of organophosphorus pesticides is associated with decreased acetylcholinesterase activity, hepatic dysfunction and disturbance of amino acids profile. Biochemical indices of hepatocellular injury and disturbed amino acid metabolism may be of value as markers of chronic exposure to such pesticides.
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PMID:Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides. 1002 66

The aims of the present study were to assess the changes of individual plasma amino acid levels in relation (1) to the severity of liver damage and (2) to the process of liver recovery. Acute liver injury was induced by an intragastric administration of CCl4 diluted in olive oil in doses of 2, 4 and/or 6 g of CCl4 per kg b.w. The control rats received olive oil only. Animals were sacrificed at 16, 24, 48 and 96 hours after treatment. The severity of liver injury was assessed by histological examination, by changes in ALT and AST in the blood plasma and by changes in liver weight. Statistical analysis was carried by ANOVA, p < 0.05 was considered significant. The Spearman rank correlation coefficient was used as a measure of the degree of linear relationship between variable and dose. In the period of the development of acute liver damage, i.e. at 16 and 24 hours after treatment, an increase in blood plasma amino acid levels and positive correlations with the dose of CCl4 were observed for most individual amino acids. The only exception was arginine which decreased in a dose dependent manner. At a phase of liver recovery, i.e. at 48 and 96 hours after CCl4 treatment, the concentrations of some individual amino acids decreased below the control values. The negative correlation with the dose of CCl4 occurred for taurine and isoleucine (at 48 hours) and taurine, threonine, valine, methionine, isoleucine and leucine (at 96 hours).
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PMID:Plasma amino acid levels after carbon tetrachloride induced acute liver damage. A dose-response and time-response study in rats. 1007 29

In fulminant hepatic failure (FHF), the development of hepatic encephalopathy is associated with grossly abnormal concentrations of plasma amino acids (PAA). Normalization of the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio) correlates with clinical improvement. This study evaluated changes in PAA metabolism during 4 h of isolated, normothermic extracorporeal liver perfusion using a newly designed system containing human blood and a rhesus monkey liver. Bile and urea production were within the physiological range. Release of the transaminases AST, ALT and LDH were minimal. The ratio of branched (valine, leucine, isoleucine) to aromatic (tyrosine, phenylalanine) amino acids increased significantly. These results indicate that a xenogeneic extracorporeal liver perfusion system is capable of significantly increasing Fischer's ratio and may play a role in treating and bridging patients in FHF in the future.
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PMID:Xenogeneic, extracorporeal liver perfusion in primates improves the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio). 1035 51

The contribution of amino acid oxidation to total energy expenditure is negligible during short-term intense exercise and accounts for 3-6% of the total adenosine triphosphate supplied during prolonged exercise in humans. While not quantitatively important in terms of energy supply, the intermediary metabolism of several amino acids-notably glutamate, alanine, and the branched-chain amino acids-affects other metabolites, including the intermediates within the tricarboxylic acid (TCA) cycle. Glutamate appears to be a key substrate for the rapid increase in muscle TCA cycle intermediates (TCAI) that occurs at the onset of moderate to intense exercise, due to a rightward shift of the reaction catalyzed by alanine aminotransferase (glutamate + pyruvate <==> alanine + 2-oxoglutarate). The pool of muscle TCAI declines during prolonged exercise, and this has been attributed to an increase in leucine oxidation that relies on one of the TCAI. However, this mechanism does not appear to be quantitatively important due of the relatively low maximal activity of branched-chain oxoacid dehydrogenase, the key enzyme involved. It has been suggested that an increase in TCAI is necessary to attain high rates of aerobic energy production and that a decline in TCAI may be a causative factor in local muscle fatigue. These topics remain controversial, but recent evidence suggests that changes in TCAI during exercise are unrelated to oxidative energy provision in skeletal muscle.
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PMID:Regulation of skeletal muscle amino acid metabolism during exercise. 1125 39

Stem segments prepared from pondweed (Potamo geton distinctus A. Benn.) turions (overwintering buds) elongate in anaerobic conditions, whereas there is almost no elongation in air. The anaerobic elongation was accompanied by a decrease in dry weights of stem segments, mainly due to consumption of storage starch in the amyloplasts of stem cells. On the other hand, total contents of amino acids increased in stem segments, in which contents of alanine, valine, leucine, and isoleucine increased, but contents of asparatic acid decreased. Moreover, contents of lactate in stem tissues increased at an early stage of anaerobic incubation. In tracer experiments with 14C-glucose, 14C incorporation into stem tissues in anoxia was only half of that in normoxia. However, conversion of 14C to ethanol occurred exclusively in anoxia. 14C-labelled metabolites were analysed by two-dimensional cellulose thin-layer chromatography. 14C incorporation into sucrose and alanine was significantly increased in anoxia. The activity of alanine aminotransferase was enhanced by anoxia, suggesting that pyruvate is a precursor of alanine synthesis. The results suggest that pondweed turions produce energy necessary for anaerobic elongation by activating conversion of storage starch in the amyloplasts to ethanol, alanine and lactate.
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PMID:Stimulation of glycolysis in anaerobic elongation of pondweed (Potamogeton distinctus) turions. 1217 22

The goal of this study was to determine whether a new internal bioartificial liver utilizing porcine hepatocytes can perform detoxification and other metabolic functions. Such a system might aid in treating patients with moderate to severe liver failure and prolong patient survival until a matching organ is found for transplantation. Porcine hepatocytes were attached to a microcarrier and an internal artificial liver was constructed by perfusing the hepatocytes into a polysulfon hollow fiber. The 4 experimental groups were: (a) control group, (b) microcarrier group, (c) hollow fiber group, and (d) internal bioartificial liver group. Viability of hepatocytes, alanine aminotransferase (ALT) and lactate dehydrogenase (LD) activities in the medium, urea production, diazepam transformation, protein synthesis, and glucose-6-phosphatase activity of cells were monitored during a 7-day culture period. Viability of porcine hepatocytes in the internal bioartificial liver group was maintained at >80% during the culture period, and alanine aminotransferase and lactate dehydrogenase activities did not fluctuate significantly. These enzyme activities were significantly lower in the internal bioartificial liver group than in the control or microcarrier groups. Urea production, diazepam transformation, [3H]-leucine incorporation, and glucose-6-phosphatase activity were significantly higher in the internal bioartificial liver group than in the control and hollow fiber groups. These results show that the new internal bioartificial liver produces small amounts of ALT and LD and exhibits detoxification and protein synthetic functions.
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PMID:Function of a new internal bioartificial liver: an in vitro study. 1295 46

Synthetic peptides, Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide A) and Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide B), derived from the beetle Allomyrina dichotoma defensin, have not only antimicrobial activities but also anti-inflammatory effects by inhibiting tumour necrosis factor-alpha(TNF-alpha) production. In the present study, we evaluated the lipopolysaccharide (LPS)-binding activities and the protective effects of these peptides on LPS-induced lethal shock in d-galactosamine (GalN)-sensitized mice. These peptides were shown to bind to erythrocytes coated with LPS and the binding activity of peptide A to LPS was significantly higher than those of peptide B and polymyxin B. Mice were injected intraperitoneally with peptide A or B at doses of 25, 50, 100 and 150 mg/kg before an injection of Salmonella abortusequi LPS (5 microg/kg) and GalN (1 g/kg) (LPS+GalN). All of wild-type mice died within 24 h after challenged with LPS+GalN. All of TNF-alpha-deficient mice challenged with LPS+GalN survived. An injection of peptide A immediately after challenge with LPS+GalN resulted in significantly improved survival rates in a dose dependent manner. Peptide B showed only minor protection. The levels of TNF-alpha in the ameliorated mice by peptide A were significantly lower than those of challenge control, suggesting a suppressive effect of peptide A on TNF-alpha production. Furthermore, peptide A-treated mice showed significantly lower levels of asparate aminotransferase and alanine aminotransferase when compared to challenge control. Concordantly, hemorrhage and necrosis in the liver of peptide A-treated mice were less apparent than those of untreated control mice. These results suggest that peptide A has a protective effect on LPS-induced mortality in this mouse model.
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PMID:Protective effects of antimicrobial peptides derived from the beetle Allomyrina dichotoma defensin on endotoxic shock in mice. 1639 28

The protective effect of a 30 kDa glycoprotein (GF-AS) isolated from the stem bark of Acanthopanax senticosus against acute and chronic alcohol-induced hepatotoxicity were studied. N-terminal amino acid sequence of GF-AS showed NH(2)-Val-Ala-Tyr-Pro-Trp-Ala-Gly-Phe-Ala-Leu-Ser-Leu-Glx-Pro-Pro-Ala-Gly-Tyr-. GF-AS significantly increases the activities of alcohol-metabolizing enzymes, including alcohol dehydrogenase, microsomal ethanol metabolizing system, and acetaldehyde dehydrogenase in rats acutely treated with alcohol, resulting in decreased plasma alcohol levels. GF-AS also increases the activities of antioxidant enzymes and glutathione level. Markers of liver injury induced by alcohol: elevated serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride and cholesterol, are reduced by GF-AS in both acutely and chronically treated rats. The activities of lipogenic enzymes including malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphoglucuronic acid dehydrogenase in chronic alcohol-treated rats are significantly decreased by GF-AS. Furthemore, GF-AS improves histological change in fatty liver and hepatic lesions induced by alcohol. Collectively, GF-AS may alleviate alcohol-induced hepatotoxicity through increasing ethanol and lipid metabolism, as well as antioxidant defense systems in livers injured by acute- and chronic-alcohol treatment.
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PMID:Glycoprotein isolated from Acanthopanax senticosus protects against hepatotoxicity induced by acute and chronic alcohol treatment. 1646 37

It remains unclear whether mutational patterns of the hepatitis B virus (HBV) genome are associated with the development of severe hepatitis after the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) variants during lamivudine treatment. Thirty patients with chronic hepatitis B who had YMDD variants during lamivudine therapy and were followed up subsequently while receiving lamivudine alone for at least 6 months were examined retrospectively. The lamivudine resistant mutations in the HBV polymerase gene were detected by a line probe assay, and the full-length sequences of HBV DNA were determined in some patients. Between months 5 and 33 of therapy, mutations from methionine to isoleucine at rt204 (rtM204I) were detected in 18 patients, and mutations from methionine to valine at rt204 (rtM204V) were detected in 12. The rtM204V mutations were always accompanied by mutations from leucine to methionine at rt180 (rtL180M), while rtM204I mutations were not. Baseline characteristics, alanine aminotransferase (ALT) levels, and HBV DNA levels within 6 months after the emergence of YMDD variants did not differ significantly between patients with rtM204I alone and those with rtL180M/rtM204V. No specific mutation was identified on full-length sequence analysis in three patients with a hepatitis flare. During long term follow-up, the addition of rtL180M to rtM204I was found in four patients 7-31 months after detecting the change at rt204 and was linked to increased ALT levels. In conclusion, mutational patterns of HBV DNA at the time of emergence of YMDD variants were apparently unrelated to the clinical outcomes in Japanese patients with chronic hepatitis B during lamivudine therapy.
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PMID:Mutational patterns of hepatitis B virus genome and clinical outcomes after emergence of drug-resistant variants during lamivudine therapy: analyses of the polymerase gene and full-length sequences. 1785 34


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