Aminobutyrate aminotransferase

Medina-Kauwe LK, Tobin AJ, De Meirleir L, Jaeken J, Jakobs C, Nyhan WL, Gibson KM (1999) 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J Inherit Metab Dis 22 414-427... 

PLP-dependent enzymes are inhibited by a great variety of enzyme-activated inhibitors that react by several distinctly different chemical mechanisms.11 Here are a few. The naturally occurring gabaculline mimics y-aminobutyrate (Gaba) and inhibits y-aminobutyrate aminotransferase as well as other PLP-dependent enzymes. The inhibitor follows the normal catalytic pathway as far as the ketimine. There, a proton is lost from the inhibitor permitting formation of a stable benzene ring and leaving the inhibitor stuck in the active site ... 

Nucleophilic groups from enzymes can add to double bonds, e.g., in an aminoacrylate Schiff base, or to multiple bonds present in die inhibitor. An example is y-vinyl y-aminobutyrate (4-amino-5-hexenoic acid), another inhibitor of brain y-aminobutyrate aminotransferase which is a useful anticonvulsant drug. 

Branched chain aminotransferase Gamma-aminobutyrate aminotransferase CO-Amino acid pyruvate aminotransferase Tyrosine aminotransferase Serine pyruvate aminotransferase... 

Chen and Contario [31] reported an HPLC resolution of enantiomers of vigabatrin. The samples were treated with N-f-butoxycarbonyl-L-leucine N-hdroxysuccinimide esters in the presence of sodium carbonate and then with trifluoroacetic acid. The resulting diastereoisomers were separated on a column (25 cm x 4 mm) of Lichrosorb RP-8 (10 fim) with acetonitrile-dioxan-0.5 M H3PO4 (pH 7)-acetonitrile (24 1) as mobile phase with a flow rate of 2 ml/min and detection at 210 nm. Good recoveries of the inactive R-(—)-form (0.5-2%) added to the active S-(+)-form of the aminobutyrate aminotransferase inhibitor were obtained. The results on a sample containing 0.24% of the R-(—)-form agreed with those obtained by GC. 

Kwon, O.S., Park, J., and Churchich, J.E., 1992, Brain 4-aminobutyrate aminotransferase. Isolation and sequence of a cDNA encoding the enzyme. J. Biol. Chem. 267(11) 7215-7216. 

Sterri, S.H., Fonnum, F. (1978). Isolation of organic anions by extraction with liquid anion exchangers and its application to micromethods for acetylcholinesterase and 4-aminobutyrate aminotransferase. Fur. J. Biochem. 91 215-22. 

Silverman RB, Invergo BJ. Mechanism of inactivation of y-aminobutyrate aminotransferase by 4-amino-5-fluoropentanoic acid. Eirst example of an enamine mechanism for a y-amino acid with a partition ratio of 0. Biochemistry 1986 25 6817-6820. 

A very special case of toxicity by a sulfate conjugate Is the effect of ethanolamlno-0-sulfate, which Is an irreversible "suicide" Inhibitor of 4-aminobutyrate aminotransferase. This sulfate conjugate is a substrate analogue for the enzyme, which, because of the electronegativity of the sulfate group, is converted by 8-ellminatlon... 

Fowler J. and John R A (1972) Active-site-directed irreversible inhibition of rat brain 4-aminobutyrate aminotransferase by ethanolamine-O-sulphate in vitro and in vivo. Biochem. ] 130, 569-573. 

E. Gamma-aminobutyric acid (GABA) Glutamate decarboxylase Aminobutyrate aminotransferase... 

D.G. De Gracia and B. Jolles-Bergeret. Sulfinic and sulfonic analogs of T i inobutyric acid and succinate semialdehyde, new substrates for the aminobutyrate aminotransferase and the succinate semialdehyde dehydrogenase of Pseudomonas Fluorescens. Biochim. Biophys. Acta, 1973, 315 49. 

Choi, S. Y. Churchich, J. E. 4-Aminobutyrate aminotransferase reaction of sulfhydryl residues connected with catalytic activity. J. Biol. Chem. 1985, 260,993-997. 

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