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.
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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.
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PMID:Effect of dietary protein on pyrimidine-metabolizing enzymes in rats. 180 76

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.
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PMID:Inhibitory effect of 6-azauracil on beta-alanine metabolism in rat. 263 79

To evaluate the significance of inborn metabolic disorders of the pyrimidine degradation pathway, 450 children with unspecific neurological symptoms were comprehensively studied; 200 healthy children were recruited as controls. Uracil and thymine as well as their degradation products in urine were determined with an improved method based on reversed-phase HPLC coupled with electrospray ionization tandem mass spectrometry and detection by multiple-reaction monitoring using stable-isotope-labelled reference compounds as internal standards. From the results of the control group we established age-related reference ranges of all pyrimidine degradation products. In the patient group, two children with dihydropyrimidine dehydrogenase (DPYD) deficiency were identified; one of these was homozygous for the exon 14-skipping mutation of the DPYD gene. In addition, two patients with high uracil, dihydrouracil and beta-ureidopropionate were found to have ornithine transcarbamylase deficiency. In the urine of 9 patients, beta-alanine was markedly elevated owing to treatment with vigabatrin, an irreversible inhibitor of GABA transaminase, which interferes with beta-alanine breakdown. Four patients had exclusively high levels of beta-aminoisobutyrate (beta-AIB) due to a low activity of the D-beta-AIB-pyruvate aminotransferase, probably without clinical significance. In conclusion, quantitative investigation of pyrimidine metabolites in children with unexplained neurological symptoms, particularly epileptic seizures with or without psychomotor retardation, can be recommended as a helpful tool for diagnosis in clinical practice. Sensitive methods and age-related reference ranges enable the detection of partial enzyme deficiencies.
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PMID:Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry. 1643 4