Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.19 (GABA transaminase)
 808 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among pyrimidine derivatives, we found that 5-fluorouracil potently inhibited purified rat liver D-3-aminoisobutyrate-pyruvate aminotransferase, whereas 5-fluorouridine did so to a much lesser extent. 5-Fluorouracil acted as a competitive inhibitor against beta-alanine with a Ki of 56 microM, and was uncompetitive against pyruvic acid, with a Ki of 73 microM. alpha-Fluoro-beta-alanine, a metabolite of 5-fluorouracil, was also a competitive inhibitor with respect to beta-alanine with a Ki of 8.0 mM. 5-Fluorouracil acted also as a competitive inhibitor of 4-aminobutyrate aminotransferase with respect to beta-alanine with a Ki value of 1.9 mM, and was uncompetitive against 2-oxoglutaric acid, with a Ki of 1.8 mM.
 ...
PMID:Inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by 5-fluorouracil and alpha-fluoro-beta-alanine. 163 95

The effect of dietary protein on pyrimidine-metabolizing enzymes was studied in the rat. The activities of dihydropyrimidine dehydrogenase and beta-ureidopropionase in the livers of rats fed a protein-free diet were significantly decreased, while the activity of dihydropyrimidinase was unaffected. Protein deficiency (5%) also decreased the activity of beta-ureidopropionase. On the other hand, a high-protein diet (60%) increased the level of beta-ureidopropionase. The activities of beta-alanine-oxoglutarate aminotransferase (aminobutyrate aminotransferase) and D-3-aminoisobutyrate-pyruvate aminotransferase ((R)-3-amino-2-methylpropionate-pyruvate aminotransferase), which are present in mitochondria, depended on the amount of protein in the diet. Ammonium ions supplemented in the diet and given by injection did not affect the activities of rat liver pyrimidine-metabolizing enzymes (dihydropyrimidine dehydrogenase, dihydropyrimidinase, beta-ureidopropionase, beta-alanine-oxoglutarate aminotransferase and D-3-aminoisobutyrate-pyruvate aminotransferase). Dietary uridine resulted in the accumulation of uracil in the liver, but did not affect the activities of pyrimidine-metabolizing enzymes.
 ...
PMID:Effect of dietary protein on pyrimidine-metabolizing enzymes in rats. 180 76

The conversion of (R)- to (S)-beta-aminoisobutyrate was observed in the presence of D-3-aminoisobutyrate-pyruvate aminotransferase, aminobutyrate aminotransferase, pyruvate and L-glutamate. The reverse reaction was also found in the presence of 2-oxoglutarate and L-alanine. Neither D-3-aminoisobutyrate-pyruvate aminotransferase nor aminobutyrate aminotransferase revealed a racemase activity of the enantiomorphs.
 ...
PMID:Evaluation of interconversion between (R)- and (S)-enantiomers of beta-aminoisobutyrate. 197 65

Gabaculine, 5-amino-1,3-cyclohexadienylcarboxylate, is an analogue of GABA and a potent irreversible inhibitor of GABA aminotransferase. However, D-3-aminoisobutyrate-pyruvate aminotransferase for which GABA was neither a substrate nor an inhibitor was also inactivated by gabaculine. The Ki for D-3-aminoisobutyrate-pyruvate aminotransferase was 8.3 x 10(-6) M, and the Kcat for its turnover was 0.31 min-1 at 25 degrees C. beta-Alanine protected the enzyme from inactivation by gabaculine, but GABA did so to much a lesser extent.
 ...
PMID:Irreversible inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by gabaculine. 212 4

The effect of 6-azauracil on beta-alanine metabolism was investigated in vivo in the rat. Both of the enzymes beta-alanine-oxoglutarate aminotransferase (aminobutyrate aminotransferase) and D-3-aminoisobutyrate-pyruvate aminotransferase [R)-3-amino-2-methylpropionate-pyruvate aminotransferase), which are beta-alanine catabolizing enzymes from rat liver and kidney, were inactivated by 6-azauracil injection, while dihydrouracil dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase, which are pyrimidine metabolizing enzymes, were not affected. The content of beta-alanine was increased, but the level of uridine and uracil in rat liver was not affected, by 6-azauracil. When a crude enzyme preparation was passed through a Sephacryl S-200 column, both enzymes could be separated from each other. beta-Alanine-oxoglutarate aminotransferase and beta-alanine-pyruvate aminotransferase activities in rat liver decreased to 27.4% and 63.9%, respectively, upon 6-azauracil injection, and those in kidney were 11.7% and 38.3%, respectively. From these findings, it is suggested that the accumulation of beta-alanine in 6-azauracil-treated rat liver might be caused by the inhibition of beta-alanine catabolizing enzymes, but not by an increase in the uridine pool nor by the activation of pyrimidine metabolism.
 ...
PMID:Inhibitory effect of 6-azauracil on beta-alanine metabolism in rat. 263 79

Alanine-glyoxylate aminotransferase (AGT) 2 is a pyridoxal 5'-phosphate dependent, mitochondrial enzyme which, in the rat, is expressed at a high level in the kidney. The amino acid sequences of nine tryptic and seven CNBr peptides of the rat kidney AGT2 were determined. Three overlapping cDNAs encoding the AGT2 were cloned on the basis of its partial amino acid sequences by means of a polymerase chain reaction-based approach involving rat kidney poly(A)+ RNA. The complete cDNA sequence comprised 1,919 bases, and contained a 1,536-base open reading frame which encodes a polypeptide of 512 amino acid residues with a putative presequence consisting of 39 amino acid residues at the amino terminus, giving a precursor protein with a molecular mass of 57,150 Da. The sequence of AGT2 exhibits significant homology with neither peroxisomal AGT1 from human liver nor mitochondrial AGT1 from rat liver. However, the sequence of AGT2 exhibited 30.8, 29.2, and 27.1% identity with those of Escherichia coli 4-aminobutyrate aminotransferase, rat ornithine aminotransferase, and Pseudomonas cepacia 2,2-dialkylglycine decarboxylase, respectively. The active site sequences were also well conserved among these aminotransferases. AGT2, thus, is more similar to the other aminotransferases than to AGT1. The results suggest that the rat kidney AGT2 may play a biological role in amino acid metabolism distinct from that of AGT1.
 ...
PMID:Molecular cloning and sequencing of a cDNA encoding alanine-glyoxylate aminotransferase 2 from rat kidney. 759 50

D-3-Aminoisobutyrate-pyruvate aminotransferase (EC 2.6.1.40) and alanine-glyoxylate aminotransferase 2 (EC 2.6.1.44) were co-purified from rat liver as a single protein. The ratio of the two activities remained constant after Sephacryl S-200 chromatography and chromatofocussing. The Km value for beta-alanine as a substrate with 1 mM glyloxylate as amino group acceptor was 1.4 mM. The activity was inhibited by (S)-alanine with Ki = 2.2 mM. The Km for (S)-alanine as substrate with 1 mM glyoxylate as amino group was 6 mM. This activity was inhibited competitively by beta-alanine with Ki = 0.7 mM. (R)-3-aminoisobutyric acid, 5-aminolevulinic acid, NG,NG'-dimethyl-(S)-arginine, and (S)-2-aminobutyric acid were active competitively with respect to beta-alanine with Km of 0.12 mM, 2.1 mM, 6.4 mM and 11.3 mM, respectively. Antiserum to rat liver D-3-aminoisobutyrate-pyruvate aminotransferase inhibited alanine-glyoxylate aminotransferase activity in rat liver in the same way as that of D-3-aminoisobutyrate-pyruvate aminotransferase. Alanine-glyoxylate aminotransferase activity and D-3-aminoisobutyrate-pyruvate aminotransferase activities were inactivated competitively with respect to beta-alanine by 5-fluorouracil and 6-azauracil, which are chemotherapeutic reagents used to cancer. These experiments indicate that D-3-aminoisobutyrate-pyruvate aminotransferase is identical with alanine-glyoxylate aminotransferase 2, aminolevulinate aminotransferase, 2-aminobutyrate aminotransferase and dimetylarginine-pyruvate aminotransferase.
 ...
PMID:Identity of D-3-aminoisobutyrate-pyruvate aminotransferase with alanine-glyoxylate aminotransferase 2. 842 75

Ethanol in the presence of disulfiram (N,N,N',N'-tetraethylthiuram disulfide, an inhibitor of aldehyde dehydrogenase) inhibited liver beta-alanine-oxoglutarate aminotransferase (beta-AlaAT I) activity yet activated tyrosine aminotransferase (TAT) in weanling rats in vivo. The effect on beta-AlaAT I was followed by the inhibitory expression of beta-AlaAT I mRNA. The beta-AlaAT I activity was reduced with a pseudo-first-order profile with time, and the half-life was calculated to be 12.3 +/- 0.83 h with the rate constant (Kd) of 0.056 +/- 0.004 h-1. The synthesis of beta-AlaAT I in rat liver was estimated to be 1.56 x 10(-10) mol/g of wet tissue per hour at a steady state. A combination of ethanol and disulfiram also reduced beta-alanine-pyruvate aminotransferase (beta-AlaAT II) activity to 60% of the control after 24 h.
 ...
PMID:Inhibitory effect of ethanol administration on beta-alanine-2-oxoglutarate aminotransferase (GABA aminotransferase) in disulfiram-pretreated rats. 959 Dec 43