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)

Incubation of rat brain 4-aminobutyrate aminotransferase with 4-amino-hex-5-enoic acid, a substrate analog of 4-aminobutyric acid, results in a time-dependent irreversible loss of enzymatic activity. In the presence of 0.1 mM inhibitor the half-life of the inactivation process is approximately 6 min. Low concentrations of L-glutamic acid or 4-aminobutyric acid protect against this inactivation, while 2-oxoglutarate prevents this protection, suggesting that only the pyridoxal form of the enzyme is susceptible to inhibition by 4-amino-hex-5-enoic acid. The irreversible inhibition of mammalian 4-aminobutyrate aminotransferase by 4-amino-hex-5-enoic acid is selective. There is no inhibition of this enzyme from Pseudomonas fluorescens with the inhibitor at mM concentrations. Even at 10 mM there is no irreversible inhibition of mammalian glutamate decarboxylase or of aspartate aminotransferase, while alanine aminotransferase is inhibited over 500 times more slowly than rat brain 4-aminobutyrate transaminase.
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PMID:4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. 85 82

A severe compression craniocerebral trauma was induced in rats under short-term halothane anesthesia. The activity of pyruvate and 2-oxoglutarate dehydrogenase complexes reduced significantly in the tissue of the damaged hemisphere, ALT activity increased sharply, AST activity grew slowly, the production of GABA in the glutamate decarboxylase reaction was slightly inhibited and its utilization in the GABA transaminase reaction was clearly accelerated. The GABA level in the nerve tissue showed a tendency to reduce, while the glutamate level had a tendency to increase. The observed changes are evidence that the inclusion of the GABA skeleton in the reaction of further oxidation intensifies, which may be of significance in compensation of the transport of the energetically oxidizing succinate and, possibly, in the formation of endogenous GABA possessing a stress-relieving effect.
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PMID:[The compensatory function of a GABA shunt in brain energy metabolism in measured craniocerebral trauma in rats]. 290 62

1. Partially purified preparations of rat brain 4-aminobutyrate aminotransferase were inhibited in a time-dependent manner by ethanolamine O-sulphate. The inhibition was not reversed by dialysis. 2. The inhibitor formed an initial reversible complex with the enzyme (K(i)=4.4x10(-4)m) and the rate of inactivation followed pseudo-first-order kinetics (k=7.15x10(-4)s(-1)). The inclusion of 4-aminobutyrate markedly slowed the rate of inactivation. 3. Ethanolamine O-sulphate did not inhibit glutamate decarboxylase, alanine aminotransferase or aspartate aminotransferase. 4. Intracisternal injection of ethanolamine O-sulphate into rats led to rapid inactivation of 4-aminobutyrate aminotransferase in vivo.
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PMID:Active-site-directed irreversible inhibition of rat brain 4-aminobutyrate aminotransferase by ethanolamine O-sulphate in vitro and in vivo. 466 81

beta-Methylene-DL-aspartate, a new beta, gamma-unsaturated amino acid, is an irreversible inhibitor of soluble pig heart glutamate-aspartate transaminase (Ki approximately 3 mM with respect to the L-form; limiting rate constant for inactivation approximately 0.4 min-1). The new amino acid is the most specific inhibitor of glutamate-aspartate transaminase thus far studied. It does not inactivate pig heart glutamate-alanine transaminase, soluble rat kidney glutamine transaminase K, gamma-aminobutyrate transaminase (from Pseudomonas fluorescens), glutamate decarboxylase (Escherichia coli), snake venom L-amino acid oxidase, or hog kidney D-amino acid oxidase. In addition, the following enzymes were not inhibited by beta-methylene-DL-aspartate in rat tissue homogenates: gamma-aminobutyrate transaminase (brain), tyrosine transaminase (liver), glutamine transaminase L (liver), asparagine, transaminase (liver), ornithine transaminase (liver) or branch-chain transaminase(s) (kidney). Intraperitoneal injection of beta-methylene-DL-aspartate into mice decreased kidney and liver glutamate-aspartate transaminase activities but had no effect on liver glutamate-alanine transaminase activity.
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PMID:Inhibition of glutamate-aspartate transaminase by beta-methylene-DL-aspartate. 683 Jun 31

The effects of intraperitoneal administration of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based covalent inactivator of gamma-aminobutyric acid transaminase (GABA-T), on whole brain GABA metabolism in mice were investigated. A dose-dependent and time-dependent irreversible inactivation of GABA-T was observed with a concomitant increase in whole brain GABA levels. The compound exhibited no in vitro nor in vivo time-dependent inhibition of glutamate decarboxylase (GAD), alanine transaminase, or aspartate transaminase (Asp-T). It was, however, a potent competitive reversible inhibitor of GAD and a weak competitive inhibitor of Asp-T. The chloro analogue, (S)-4-amino-5-chloropentanoic acid, was ineffective.
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PMID:In vitro and in vivo effects on brain GABA metabolism of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based inactivator of gamma-aminobutyric acid transaminase. 685 67

The aim of the present study is to compare normal and tumoral pancreatic islet cells in terms of both the activity of selected cytosolic and mitochondrial enzymes participating to nutrient catabolism and the intrinsic properties of FAD-glycerophosphate dehydrogenase. The activity of the glycolytic enzymes hexokinase and lactate dehydrogenase was higher in tumoral (RINm5F) than normal islet cells. The opposite was seen for glutamate decarboxylase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, glutamate dehydrogenase, 2-ketoglutarate dehydrogenase and FAD-glycerophosphate dehydrogenase (m-GDH). These findings are consistent with the high rates of glycolysis and protein synthesis seen in tumoral islet cells compared with normal islet cells, which favour mitochondrial oxidative events associated with the catabolism of D-glucose and amino acids. The intrinsic catalytic properties of m-GDH were comparable, albeit not identical, in normal and tumoral islet cells. Since a deficiency of m-GDH in pancreatic islets may represent a contributing factor in the pathogenesis of non-insulin-dependent diabetes, it is proposed that RINm5F cells may readily yield sufficient islet m-GDH for purification and further gene cloning.
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PMID:Activity of cytosolic and mitochondrial enzymes participating in nutrient catabolism of normal and tumoral islet cells. 776 86

Chronic acidosis evoked by a 7-day application of ammonium chloride in concentration of 2% increased the activity of glutamate decarboxylase (GAD) in renal homogenates of rats to approximately 160%. The enzyme activators, chlorides and adenosine triphosphate influenced in varying measures the GAD activity in renal homogenates of both controlled and acidotic animals. Whilst ATP was gradually loosing the activating effect, chlorides preserved it. The renal GAD is firmly bound on insoluble structures. The increase in GAD activity due to acidosis was accompanied by increasing permanence of this bind. After the substitution of ammonium chloride by drinking water, the return of the increased GAD activity to previous normal values lasted 7 days, whilst apparent normalization of the weight of experimental animals reoccurred on the first day. Subfractionation of the crude renal mitochondrial fraction by use of enzyme markers localized GAD in mitochondria. In renal homogenates the activities of GABA-transaminases were assessed. GABA-alpha-ketoglutarate transaminase was 5x more active than GABA-pyruvate transaminase. Acidosis resulted in augmentation of both transaminases--the first to 130%, the second to 160%. (Tab. 5, Fig. 3, Ref. 25.)
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PMID:[The effect of chronic acidosis on the activity of renal glutamate decarboxylase and GABA-transaminase]. 788 63

The C57BL/10 SPS/sps mouse mutant are audiogenic seizure-susceptible. The enzymatic activities of glutamate decarboxylase (GAD), GABA aminotransferase (GABA-T), alanine aminotransferase (ALA-T), aspartate aminotransferase (ASP-T), and glutamate dehydrogenase (GDH) of whole brain supernatant are significantly reduced in these epileptic mice. GABA uptake is decreased in cortex, midbrain, and pons medulla. Previous studies showed the presence of two sodium-dependent GLU uptake systems in normal (SPS/SP) mice. Glutamate Umax by System 1 is significantly decreased in these mice, whereas the Umax value for System 2 is significantly increased in the epileptic mice.
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PMID:Altered GABAergic and glutamatergic transmission in audiogenic seizure-susceptible mice. 788 3

The functional efficacies of inhibitors of L-glutamate uptake for altering second messenger formation in baby hamster kidney cells expressing subtypes mGluR1a, mGluR2, and mGluR4 of the metabotropic glutamate receptor family were examined. L-Serine-O-sulfate was an agonist at mGluR1a (EC50 = 70 microM), mGluR2 (EC50 = 25 microM), and mGluR4 (EC50 = 324 microM). L-Cysteine sulfinate, 1-aminocyclobutane-trans-1,3-dicarboxylate, L-cysteine, and DL-threo-3-methylaspartate stimulated phosphoinositide hydrolysis in mGluR1a cells with EC50 values of 43, 64, 463, and 488 microM, respectively, and displaced L-[3H]glutamate binding from membranes prepared from these cells with respective IC50 values of 48, 44, 79, and 139 microM. However, D-aspartate, L-trans-pyrrolidine-2,4-dicarboxylate, L-threo-3-hydroxyaspartate, and L-aspartate-beta-hydroxamate stimulated phosphoinositide hydrolysis in mGluR1a cells (respective EC50 values of 73, 54, 57, and 430 microM) but did not displace L-[3H]glutamate binding. These compounds inhibited Na(+)-dependent L-glutamate uptake into baby hamster kidney cells with IC50 values similar to those for stimulation of phosphoinositide hydrolysis in mGluR1a cells. Phosphoinositide hydrolysis in mGluR1a cells, as stimulated by inhibitors of (or substrates for) this L-glutamate transporter, was significantly attenuated in the presence of L-glutamate decarboxylase (EC 4.1.1.15) or L-alanine aminotransferase (EC 2.6.1.2). Furthermore, incubation with 1 mM L-trans-pyrrolidine-2,4-dicarboxylate for 30 min increased the basal levels of free glutamate (1.5 +/- 0.2 microM) in the assay buffer four- to fivefold as measured by HPLC analysis. Thus, heteroexchange with endogenous L-glutamate may lead to erroneous estimations of the functional efficacies at mGluR1a.
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PMID:L-glutamate uptake inhibitors may stimulate phosphoinositide hydrolysis in baby hamster kidney cells expressing mGluR1a via heteroexchange with L-glutamate without direct activation of mGluR1a. 796 21

Islets were isolated by automatic digestion from non-diabetic cadaveric organ donors and from Type 2 (non-insulin-dependent) diabetic subjects. The activity of FAD-glycerophosphate dehydrogenase, but not that of either glutamate dehydrogenase, glutamate-oxalacetate transaminase or glutamate-pyruvate transaminase, was lower in Type 2 diabetic patients than control subjects. Hexokinase, glucokinase and glutamate decarboxylase activities were also measured in islets from control subjects. The utilization of D-[5-3H]glucose, oxidation of D-[6-14C]glucose and release of insulin evoked by D-glucose were all lower in Type 2 diabetic patients than control subjects. The secretory response to the combination of L-leucine and L-glutamine appeared less severely affected. Islets from Type 2 diabetic patients may thus display enzymatic, metabolic and secretory anomalies similar to those often observed in animal models of Type 2 diabetes, including a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle.
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PMID:Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients. 816 52


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