Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacillus cereus strain K-22 produced two distinct omega-amino acid transaminases, one catalyzing the transamination between beta-alanine and pyruvic acid and the other that between gamma-aminobutyric acid and alpha-ketoglutaric aic. The two enzymes were partially purified and separated from each other by various chromatographies. beta-Alanine:pyruvic acid transaminase and gamma-aminobutyric acid:alpha-ketoglutaric acid transaminase were induced by the addition of beta-alanine and gamma-aminobutyric acid, respectively, to the growth medium. beta-Alanine transaminase showed an optimum pH of 10.0 and optimum temperature of 35 degrees C, and its Km values for beta-alanine and pyruvic acid were both 1.1 mM. gamma-Aminobutyric acid, epsilon-aminocaproic acid, 2-aminoethylphosphonic acid, and propylamine showed about 30-40% of the activity of beta-alanine as amino donors, and oxalacetic acid was as good an amino acceptor as pyruvic acid. The optimum pH and temperature of gamma-aminobutyric acid transaminase were 9.0 and 50 degrees C, respectively, and its Km value for gamma-aminobutyric acid was 2.8 mM, while that for alpha-ketoglutaric acid was 2.3 mM. gamma-Aminobutyric acid and delta-aminovaleric acid were good amino donors but other omega-amino acids were virtually inactive with gamma-aminobutyric acid transaminase; alpha-ketoglutaric acid, and to a lesser extent glyoxylic acid, were active amino acceptors. Sulfhydryl reagents specifically activated gamma-aminobutyric acid transaminase.
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PMID:Two omega-amino acid transaminases from Bacillus cereus. 1 32

Gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid), a naturally occurring amino acid isolated from Streptomyces toyacaenis, is an irreversible inhibitor of bacterial pyridoxal phosphate linked gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase with a t 1/2 (25 degrees C) of 9 min at 3 X 10(-7) M. Gabaculine is a substrate for gamma-aminobutyric acid transaminase. The measured KI is 2.86 X 10(-6) M, and the kcat for its turnover is 1.15 X 10(-2) S-1 at 25 degrees C. When gabaculine is transaminated by the enzyme, it is converted to a cyclohexatrienyl system with one exo double bond. Upon spontaneous aromatization, this high energy intermediate is transformed into a stable m-anthranilic acid derivative (m-carboxyphenylpyridoxamine phosphate), which results in the covalent and irreversible modification of the cofactor. This adduct is bound tightly to the active site of the enzyme and can be liberated under denaturing conditions.
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PMID:Mechanism of the irreversible inhibition of gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase by the neutrotoxin gabaculine. 41 Apr 42

4-Aminobutyrate:2-oxoglutarate (4-aminobutyrate:2-oxoglutarate amino-transferase, EC 2.6.1.19) from human brain has been purified 2500-fold with respect to the initial homogenate. The enzyme, which appears to be pure by polyacrylamide gel electrophoresis, N-terminal analysis and immunodiffusion, was compared to rat brain 4-aminobutyrate transaminase, purified to the same extent in an earlier study [15]. The two enzymes, which have approximately the same molecular weight, show large differences in their tryptic fingerprints and in the peptides produced by cyanogen bromide cleavage. The Km values (limit) for 4-aminobutyrate are different, the human enzyme having four times greater affinity for this substrate. A series of branched-chain fatty acids (including n-dipropylacetate), which are structural analogues of 4-aminobutyrate and inhibit rat brain 4-aminobutyrate transaminase, are less powerful inhibitors of the human enzyme.
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PMID:Comparison of the structural characteristics of the 4-aminobutyrate:2-oxoglutarate transaminases from rat and human brain, and of their affinities for certain inhibitors. 62 69

The administration of L-cycloserine to mice resulted in a dramatic decrease in the activities of 4-aminobutyrate:2-oxoglutarate aminotransferase (GABA-T) and L-alanine:2-oxoglutarate aminotransferase (ALA-T) in both brain and liver. L-Aspartate:2-oxoglutarate aminotransferase was inhibited only slightly, and brain glutamic acid decarboxylase not at all. Liver ALA-T activity returned to near normal levels within 24 h of L-cycloserine administration whereas liver GABA-T and brain ALA-T activities had returned only halfway to normal levels in the same time period. The recovery in the activity of brain GABA-T was even slower. A consequence of the inhibition of brain GABA-T activity was an elevation in the GABA content of the tissue which was maximal 3 h after L-cycloserine administration and which was still noticeable 8 h after the drug treatment. L-Cycloserine was also a potent in vitro inhibitor of brain GABA-T activity. The inhibition was competitive with respect to GABA, the Ki value being 3.1 X 10(-5) M. The prior administration of L-cycloserine to mice significantly delayed the onset of isonicotinic acid hydrazide induced convulsions.
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PMID:Effect of L-cycloserine on brain GABA metabolism. 63 58

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

In the belief that homocysteine-induced convulsions might be related to alterations in brain gamma-aminobutyric acid metabolism, we have studied the action of this amino acid on the activity of glutamic decarboxylase (GAD, EC 4.1.1.15) and gamma-aminobutyrate aminotransferase (EC 2.6.1.19) of mouse brain in vitro DL-homocysteine competitively inhibited GAD with respect to both L-glutamate and pyridoxal 5'-phosphate. The respective Ki's were 3.8 mM and 0.3 mM. The activity of GABA-T also was altered in the presence of DL-homocysteine. A competitive inhibition (Ki = 6 mM) was observed with gamma-aminobutyric acid, and an uncompetitive inhibition with respect to pyridoxal 5'-phosphate and alpha-ketoglutarate. These results are explained in terms of a dual action of homocysteine on each of the enzymes: one involving a competition for substrate binding site and the other involving the formation of an inactive inhibitor-cofactor complex. The significance of the inhibition of these enzymes of gamma-aminobutyric acid metabolism is discussed in relation to the convulsant action of homocysteine.
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PMID:The mode of action of homocysteine on mouse brain glutamic decarboxylase and gamma-aminobutyrate aminotransferase. 90 1

The effects of DL-penicillamine (DL-PeA), hydrazine and toxopyrimidine (TXP, 2-methyl-6-amino-5-hydroxymethylpyrimidine) on gamma-aminobutyric acid (GABA) metabolism in mouse brain were studied. All these compounds inhibited the activity of glutamate decarboxylase [EC 4.1.1.15] (GAD) and slightly inhibited that of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 2.6.1.19] (GABA-T). In contrast, very different effects were observed on GABA levels; hydrazine caused a marked increase, DL-PeA had no effect, and TXP caused a slight decrease in the content of the amino acid. These results could be described by an equation which related the excitable state to changes in the flux of the GABA bypass. Since the values obtained from the equation clearly reflect the seizure activity, it is suggested that the decreased GABA flux might be a cause of convulsions induced by these drugs.
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PMID:A correlation between changes in gamma-aminobutyric acid metabolism and seizures induced by antivitamin B6. 100 83

The effects of sodium cyanide (NaCN) on the gamma-aminobutyric acid metabolizing enzymes glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) were studied in vitro. With no pyridoxal-5-phosphate added, GAD was non-competitively inhibited by NaCN, with an IC50 of 280 microM. GAD was also inhibited when exposed to an equimolar amount of NaCN and pyridoxal-5-phosphate. NaCN inhibited GABA-T. The inhibition kinetics suggests that NaCN may react with more than one of the substrates and products present during the reaction, i.e. pyridoxal-5-phosphate, alpha-ketoglutarate and/or succinic semialdehyde. The presence of pyridoxal-5-phosphate in the reaction mixture completely protected GABA-T from inhibition by NaCN. The gamma-aminobutyric acid synthesizing enzyme, GAD may thus be inhibited in vivo by NaCN or by a reaction product of NaCN and pyridoxal-5-phosphate. The gamma-aminobutyric acid catabolizing enzyme, GABA-T is not as vulnerable to inhibition by NaCN, since the cyanide-pyridoxal-5-phosphate complex is ineffective as inhibitor.
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PMID:On the inhibition of glutamic acid decarboxylase and gamma-aminobutyric acid transaminase by sodium cyanide. 195 76

The effects of dopamine D1 and D2 receptor agonists and antagonists on the rate of GABA synthesis in four regions of mouse brain (corpus striatum, cerebellum, cortex and hippocampus) were examined after irreversible inhibition of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T) by gabaculine. The dopamine D2 receptor agonists PPHT, LY 171555 and RU 24213 exerted a dose-related inhibitory effect on GABA synthesis in these four regions. The decreases in the rate of GABA formation were prevented by the dopamine D2 receptor antagonist S(-)-sulpiride. The dopamine D1 receptor agonists SKF 77434 and SKF 38393 augmented gabaculine-induced GABA accumulation in the corpus striatum only, and this effect was blocked by the dopamine D1 receptor antagonist SCH 23390. However, SKF 81297 and SKF 82958, two other dopamine D1 receptor agonists, did not affect or only marginally altered the rate of GABA synthesis. Stimulation of D2 receptors thus induces a decrease in the rate of GABA formation in the four brain areas examined, whereas stimulation of D1 receptors either increases GABA synthesis in the corpus striatum or does not alter it. This effect appears to be independent of the degree of receptor occupancy.
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PMID:Effects of selective dopamine D1 and D2 receptor agonists on the rate of GABA synthesis in mouse brain. 198 57

The activity of 4-aminobutyrate:2-oxoglutarate transaminase (GABA-T) has been investigated in the rat and human brain. Both rat and human brain GABA-T retained its full activity for at least 2 months and with a loss of less than 10% after 6 months when frozen at -20 degrees C as tissue parts. There was a loss of activity of mouse brain GABA-T of about 15% per 24 hours postmortem. In the rat brain, GABA-T activity varied from low values in cortex and hippocampus to high in brain stem and cerebellum. There was a significant increase of GABA-T activity with age from 1 to 6 weeks and a significant reduction of the activity with age thereafter. Male rats had significant higher activity than female rats. In the human brain, GABA-T activities were measured in twelve regions of autopsied brains from 10 adult control subjects. No difference was found between the activities in the left and right sides. There is considerable variation in enzyme activity across the brain, with low activities in e.g. pons and medulla oblongata and high activities in e.g. caudatus, substantia nigra and hypothalamus. The activity of the enzyme is significantly different both between brain regions and between individuals.
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PMID:GABA-transaminase activity in rat and human brain: regional, age and sex-related differences. 205 53


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