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)

Leucine and monomethyl succinate initiate insulin release, and glutamine potentiates leucine-induced insulin release. Alanine enhances and malate inhibits leucine plus glutamine-induced insulin release. The insulinotropic effect of leucine is at least in part secondary to its ability to activate glutamate oxidation by glutamate dehydrogenase (Sener, A., Malaisse-Lagae, F., and Malaisse, W. J. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 5460-5464). The effect of these other amino acids or Krebs cycle intermediates on insulin release also correlates with their effects on glutamate dehydrogenase and their ability to regulate inhibition of this enzyme by alpha-ketoglutarate. For example, glutamine enhances insulin release and islet glutamate dehydrogenase activity only in the presence of leucine. This could be because leucine, especially in the presence of alpha-ketoglutarate, increases the Km of glutamate and converts alpha-ketoglutarate from a noncompetitive to a competitive inhibitor of glutamate. Thus, in the presence of leucine, this enzyme is more responsive to high levels of glutamate and less responsive to inhibition by alpha-ketoglutarate. Malate could decrease and alanine could increase insulin release because malate increases the generation of alpha-ketoglutarate in islet mitochondria via the combined malate dehydrogenase-aspartate aminotransferase reaction, and alanine could decrease the level of alpha-ketoglutarate via the alanine transaminase reaction. Monomethyl succinate alone is as stimulatory of insulin release as leucine alone, and glutamine enhances the action of both. Succinyl coenzyme A, leucine, and GTP are all bound in the same region on glutamate dehydrogenase, where GTP is a potent inhibitor and succinyl coenzyme A and leucine are comparable activators. Thus, the insulinotropic properties of monomethyl succinate could result from it increasing the level of succinyl coenzyme A and decreasing the level of GTP via the succinate thiokinase reaction.
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PMID:Regulation of insulin release by factors that also modify glutamate dehydrogenase. 304 28

beta-Alanine aminotransferase from rat liver was purified to electrophoretic homogeneity. The immunological and kinetic properties of this enzyme were similar to those of the enzyme from rat brain. However, the liver enzyme transaminates from beta-alanine to 2-oxoglutaric acid, while the brain enzyme transaminates from gamma-aminobutyric acid. beta-Alanine aminotransferase activity in regenerating rat liver was lower than that in control rat liver. Activity of this enzyme, as well as of other uracil-catabolizing enzymes (Weber, G., Queener, S.F. and Ferdinandus, A. (1970) in Advances in Enzyme Regulation (Weber, G., ed.), Vol. 9, pp. 63-95, Pergamon Press, Oxford), was low in newborn rat liver and increased about 5-fold, reaching the level observed in adult rat liver. beta-Alanine and prednisolone induced beta-alanine aminotransferase in rat liver.
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PMID:The level of beta-alanine aminotransferase activity in regenerating and differentiating rat liver. 308 24

The effects of total ischemia and subsequent reperfusion on the formation of anaerobic metabolism products and their release into myocardial effluent were studied in isolated guinea pig hearts. During 30-min ischemia myocardial ATP and phosphocreatine decreased to 34 and 15% of the initial levels, respectively; this was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate; the succinate production being commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of lactate, alanine, succinate, creatine and pyruvate trace amounts into the myocardial effluent was observed during an early phase of the reperfusion using 1H-NMR. The rates of metabolite release reduced as follows: lactate much greater than alanine greater than succinate greater than creatine. By the 30th min of the reperfusion the decrease in these metabolites tissue contents was accompanied by the recovery of ATP and phosphocreatine levels up to 65 and 90% of the initial ones, respectively. The data obtained demonstrate that the formation and the release of succinate, alanine and creatine from the heart as well as of lactate may indicate profound disturbances in energy metabolism.
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PMID:An assessment of anaerobic metabolism during ischemia and reperfusion in isolated guinea pig heart. 337 59

The effect of ischemia on the formation of products of anaerobic metabolism and their release into the cardiac effluent in isolated perfused guinea pig hearts was studied. During 30 min normothermal ischemia, the myocardial ATP and phosphocreatine levels decreased to 34% and 15% of the initial values, respectively. The net alanine formation in ischemia was approximately a stoichiometric glutamate decrease; the increase in the tissue malate content corresponded to the aspartate----oxaloacetate----malate anaplerotic flux, the succinate production being commensurable to alpha-ketoglutaric acid formation in the alanine aminotransferase reaction. Using 1H-NMR, it was shown that the release of trace amounts of lactate, alanine, succinate, creatine and pyruvate into cardiac effluents occurred during the first 5 minutes of reperfusion. The rate of metabolite release decreased in the following order: lactate much greater than alanine greater than succinate greater than creatine. By the 30th minute of reperfusion, the decrease in the tissue levels of these metabolites to preischemic values was accompanied by the recovery of ATP and phosphocreatine to 65% and 90% of the initial levels, respectively. The data obtained suggest that the formation and release of alanine, creatine or succinate as well as lactate from ischemic myocardium may testify to significant disturbances in energy metabolism of the myocardium.
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PMID:[Formation of products of anaerobic metabolism in the ischemic myocardium]. 337 64

The contents of gamma-aminobutyric acid (GABA) and glutamate (GL) as well as GABA-aspartate- and alanine aminotransferase activities were measured in rat cerebellum, cerebral cortex and truncus cerebri 1, 3, 6, 24 and 48 hr following total-body gamma-irradiation (60Co) with a dose of 30 Gy. All the indices under study changed in a similar way in the cortex and truncus cerebri while in the cerebellum, GABA level increased and GABA-alpha-ketoglutarate aminotransfearse activity decreased 60 min after irradiation. The levels of GABA and GL in the cortex and truncus cerebri decreased immediately and increased 24 hr after irradiation. Activity of aminotransferases changed in a phase manner: changes in aspartate- and alanine aminotransferase activity were more pronounced than those of GABA-alpha-ketoglutarate aminotransferase activity and correlated with the glutamate level changes.
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PMID:[Early changes in GABA and glutamate levels and aminotransferase activity in parts of the rat brain following whole-body gamma irradiation at an absolutely lethal dose]. 389 85

The RS-isomers of beta-mercapto-alpha-ketoglutarate, beta-methylmercapto-alpha-ketoglutarate and beta-methylmercapto-alpha-hydroxyglutarate have been synthesized. Beta-Mercapto-alpha-ketoglutarate was a potent inhibitor, competitive with isocitrate and noncompetitive with NADP+, of the mitochondrial NADP-specific isozyme from pig heart (Ki = 5 nM; Km (DL-isocitrate)/Ki(RS-beta-mercapto-alpha-ketoglutarate) = 650) and pig liver, the cytosolic isozyme from pig liver (I0.5 = 23 nM), and the NADP-linked enzymes from yeast (Ki = 58 nM) and Escherichia coli (Ki = 58 nM) at pH 7.4 and with Mg2+ as activator. beta-Mercapto-alpha-ketoglutarate was also an effective inhibitor of NADP-isocitrate-dehydrogenase activity in intact liver mitochondria. beta-Mercapto-alpha-ketoglutarate was a much less potent inhibitor for heart NAD-isocitrate dehydrogenase (Ki = 520 nM) than for the NADP-specific enzyme. beta-Methylmercapto-alpha-ketoglutarate (I0.5 = 10 microM) was a much less effective inhibitor than the beta-mercapto derivative for heart NADP-isocitrate dehydrogenase. The beta-sulfur substituted alpha-ketoglutarates were substrates for the oxidation of NADPH by heart NADP-isocitrate dehydrogenase without requiring CO2. beta-Methylmercapto-alpha-hydroxyglutarate, the expected product of reduction of beta-methylmercapto-alpha-ketoglutarate, did not cause reduction of NADP+ but it was an inhibitor competitive with isocitrate for NADP-isocitrate dehydrogenase. The beta-sulfur substituted alpha-ketoglutarate derivatives were alternate substrates for alpha-ketoglutarate dehydrogenase and the cytosolic and mitochondrial isozymes of heart aspartate aminotransferase but had no effect on glutamate dehydrogenase or alanine aminotransferase.
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PMID:beta-Sulfur substituted alpha-ketoglutarates as inhibitors and alternate substrates for isocitrate dehydrogenases and certain other enzymes. 394 94

Isoenzymes of human red cell glutamate-pyruvate transaminase (GPT) were resolved by isoelectric focusing (IEF) of hemolysates in polyacrylamide gels at pH 5.0-7.0. The bands of enzyme activity required both alpha-ketoglutarate and L-alanine in the staining mixture for visualization, indicating that the bands were not lactate dehydrogenase or glutamate dehydrogenase. Phenotyping of 41 individuals by IEF, including types GPT 1, 2A, 1-2A, 1-2B, and 2A-2B, agreed with the typing results obtained by electrophoresis in starch gels and in polyacrylamide gels at acid and alkaline pH. Analysis of one kindred demonstrated autosomal codominant transmission of the rare GPT*2B gene through 3 generations. IEF facilitates phenotyping by permitting identification of the GPT types on a single gel with a considerable reduction in time and cost. Although no new variants were found in this investigation, IEF may be more powerful for the recognition of presently undetected variants of GPT.
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PMID:Identification of human red cell glutamate-pyruvate transaminase (GPT) phenotypes by isoelectric focusing. 397 56

We examined 17 lots of 2-oxoglutarate (seven acid forms, three K salt forms, and seven Na salt forms), obtained from eight commercial suppliers, for suitability for measuring aspartate aminotransferase (EC 2.6.1.1) and alanine aminotransferase (EC 2.6.1.2) in human serum. Measurements of the catalytic activity concentrations of these two aminotransferases with each of these 17 preparations were not sufficiently sensitive to distinguish good from poor-quality material. Thus, we ranked these lots for purity, by specific analysis with glutamate dehydrogenase and by liquid chromatography, and determined the water content, acid content, and spectral characteristics of each. On the basis of a 2-oxoglutarate assay value by glutamate dehydrogenase of 98% or greater, we considered seven of the preparations acceptable and 10 unacceptable. The molar absorptivities (L X mol-1 X cm-1, mean +/- SD) of the seven acceptable lots in 1 mol/L HCl were: epsilon 325 nm = 9.12 +/- 0.02 (CV = 0.2%), epsilon 279 nm = 2.63 +/- 0.23 (CV = 9.9%), and epsilon 245 nm = 37.9 +/- 4.1 (CV = 10.9%). Use of these spectrophotometric limits alone unambiguously distinguished the inferior lots of 2-oxoglutarate. We urge the inclusion of detailed spectrophotometric specifications for 2-oxoglutarate in Reference Methods for aminotransferase measurements.
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PMID:Comparisons of 17 lots of 2-oxoglutarate, and specifications for use of this substrate in reference methods. 399 57

The activity of alanine aminotransferase (ALT) phenotypes was determined in 148 hemolysates of the Serbian population. The highest activity was obtained for phenotype ALT 1 (0.614 U/g Hb), intermediate for ALT 2-1 (0.475 U/g Hb), and the lowest for ALT 2 (0.395 U/g Hb). To explain the differences in catalytic activity between the ALT phenotypes, some kinetic characteristics were investigated. No difference in heat stability and calculated activation energies for ALT phenotypes could be detected. Addition of pyridoxal 5'-phosphate to the reaction system did not increase the catalytic activity. For the catalytic activity of all three phenotypes, a broad pH optimum in the range 7.1 to 7.6 was found. The Tris/HCl buffer concentration of 140 mmol/liter was optimal. The Michaelis-Menten constants for L-alanine as substrate were 2.462 mmol/liter for ALT 1, 1.965 mmol/liter for ALT 2-1, and 2.698 mmol/liter for ALT 2. For another substrate, 2-oxoglutarate, Km values were 0.299, 0.208, and 0.202 mmol/liter, respectively.
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PMID:Some kinetic characteristics of erythrocyte alanine aminotransferase phenotypes. 400 95

1. Changes in the concentrations of ammonia, glutamine, glutamate, 2-oxoglutarate, 3-hydroxybutyrate, acetoacetate, alanine, aspartate, malate, lactate, pyruvate, NAD(+), NADH and adenine nucleotides were measured in freeze-clamped rat liver during ischaemia. 2. Although the concentrations of most of the metabolites changed rapidly during ischaemia the ratios [glutamate]/[2-oxoglutarate][NH(4) (+)] and [3-hydroxybutyrate]/[acetoacetate] changed equally and the value of the expression [3-hydroxybutyrate][2-oxoglutarate][NH(4) (+)]/[acetoacetate][glutamate] remained approximately constant, indicating that the 3-hydroxybutyrate dehydrogenase and glutamate dehydrogenase systems were at near-equilibrium with the mitochondrial NAD(+) couple. 3. The value of the expression [alanine][oxoglutarate]/[pyruvate][glutamate] was about 0.7 in vivo and remained fairly constant during the ischaemic period of 5min, although the concentrations of alanine and oxoglutarate changed substantially. No explanation can be offered why the value of the ratio differed from that of the equilibrium constant of the alanine aminotransferase reaction, which is 1.48. 4. Injection of l-cycloserine 60min before the rats were killed increased the concentration of alanine in the liver fourfold and decreased the concentration of the other metabolites measured, except that of pyruvate. During ischaemia the concentration of alanine did not change but that of aspartate almost doubled. 5. After treatment with l-cycloserine the value in vivo of the expression [alanine][oxoglutarate]/[pyruvate][glutamate] rose from 0.7 to 2.4. During ischaemia the value returned to 0.8. 6. The effects of l-cycloserine are consistent with the assumption that it specifically inhibits alanine aminotransferase. 7. Most of the alanine formed during ischaemia is probably derived from pyruvate and from ammonia released by the deamination of adenine nucleotides and glutamine. The alanine is presumably formed by the combined action of glutamate dehydrogenase and alanine aminotransferase. 8. The rate of anaerobic glycolysis, calculated from the increase in the lactate concentration, was 1.3mumol/min per g fresh wt. 9. Although the concentrations of the adenine nucleotides changed rapidly during ischaemia, the ratio [ATP][AMP]/[ADP](2) remained constant at 0.54, indicating that adenylate kinase established near-equilibrium under these conditions.
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PMID:Effects of ischaemia on metabolite concentrations in rat liver. 431 90


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