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)

The aldehyde produced from the oxidative deamination of primary and secondary amines by the monoamine oxidases (EC 1.4.3.4; MAO) or the semicarbazide-sensitive amine oxidases (EC 1.4.3.6; SSAO) may be determined followed reaction at elevated temperatures with 2-diphenylacetyl-1,3-indandione-1-hydrazone (DIH), separation by high-performance chromatography liquid (C-8 column, eluting isocratically with acetonitrile, ammonium acetate, water) and fluorimetric detection (excitation and emission wavelengths 430 and 525 nm). The detection limits for benzaldehyde, p-hydroxybenzaldehyde and 2-phenylacetaldehyde were 125 nM, 150 and 62.3 nM, respectively. Thus the assay is appropriate for determination of amine oxidase activities towards benzylamine, 2-phenylethylamine and tyramine. The fluorescence of the DIH adduct with indole-3-aldehyde was strongly quenched, giving a relatively high detection limit (17.5 microM). The detection limit was lower (3.8 microM) when the absorbance at 430 nm was monitored. Enzyme activities determined by this procedure were shown to be linear with enzyme-protein concentration (rat liver mitochondria). The presence of 1-2 mM semicarbazide, necessary for determining MAO activities in samples also containing SSAO, did not adversely affect the derivatization reaction. The DIH-aldehyde adducts were sufficiently stable to permit their storage at low temperatures prior to assay. The product produced by reaction of 5-hydroxyindole acetaldehyde with DIH had no significant fluorescence and too low an absorbance at 430 nm to allow its determination for assay of activities towards 5-HT. This procedure can also measure succinic semialdehyde (detection limit 240 nM) and thus would be applicable to the determination of GABA transaminase activity.
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PMID:Determination of monoamine oxidase activity by HPLC with fluorimetric detection. 1059 Oct 46

Epilepsy is the most common primary neurological disorder known. In the past decade, various aryl semicarbazones have been designed that were structurally dissimilar from many common anticonvulsants containing the dicarboximide function (CONRCO), which may contribute to toxic side effects. In the present work various N4-(2,6-dimethylphenyl) semicarbazones were designed as pharmacophore hybrids between the aryl semicarbazones and ameltolide. A three-dimensional four-point pharmacophore model was developed for anticonvulsants, and the title compounds were found to match with ralitoline. All of the compounds exhibited anticonvulsant activity in the maximal electroshock test when administered by both intraperitoneal and oral routes. Compound N1-(2,6-dimethylphenyl)-N4-(2-hydroxybenzaldehyde) semicarbazone (9) emerged as a prototype with wide spectrum anticonvulsant agent active in five models of seizure with no neurotoxicity and hepatotoxicity. Compound 9 increased the 4-aminobutyric acid (GABA) level by 118% and inhibited the GABA transaminase enzyme both in vitro and ex vivo.
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PMID:Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore-based design. 1619 Jul 47