Kinetic studies on the inhibition of GABA-T by gamma-vinyl GABA and taurine.
Gamma-aminobutyric acid transaminase (GABA-T, EC 2.6.1.19) is a pyridoxal phosphate (PLP) dependent enzyme that catalyzes the degradation of gamma-aminobutyric acid. The kinetics of this reaction are studied in vitro, both in the absence, and in the presence of two inhibitors: gamma-vinyl GABA (4-aminohex-5-enoic acid), and a natural product, taurine (ethylamine-2-sulfonic acid). A kinetic model that describes the transamination process is proposed. GABA-T from Pseudomonas fluorescens is inhibited by gamma-vinyl GABA and taurine at concentrations of 51.0 and 78.5 mM. Both inhibitors show competitive inhibition behavior when GABA is the substrate and the inhibition constant (Ki) values for gamma-vinyl GABA and taurine were found to be 26 +/- 3 mM and 68 +/- 7 mM respectively. The transamination process of alpha-ketoglutarate was not affected by the presence of gamma-vinyl GABA, whereas, taurine was a noncompetitive inhibitor of GABA-T when alpha-ketoglutarate was the substrate. The inhibition dissociation constant (Kii) for this system was found to be 96 +/- 10 mM. The Michaelis-Menten constant (Km) in the absence of inhibition, was found to be 0.79 +/- 0.11 mM, and 0.47 +/- 0.10 mM for GABA and alpha-ketoglutarate respectively.
Sultan Qaboos University, Department of Chemistry, College of Science, Box 36, Al-Khod 123, Sultanate of Oman.
Saba A J
SA
Sulaiman
Fakhr Eldin O
FE
Suliman
Samira
S
Barghouthi
D000612:4-Aminobutyrate Transaminase / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D013654:Taurine / Q000494:pharmacology*; D020888:Vigabatrin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013654:Taurine; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin