TY - JOUR
T1 - Kinetic studies on the inhibition of GABA-T by γ-vinyl GABA and taurine
AU - Sulaiman, Saba A.J.
AU - Suliman, Fakhr Eldin O.
AU - Barghouthi, Samira
PY - 2003/8
Y1 - 2003/8
N2 - γ-Aminobutyric acid transaminase (GABA-T, EC 2.6.1.19) is a pyridoxal phosphate (PLP) dependent enzyme that catalyzes the degradation of γ-aminobutyric acid. The kinetics of this reaction are studied in vitro, both in the absence, and in the presence of two inhibitors: γ-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 γ-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 γ-vinyl GABA and taurine were found to be 26 ± 3 mM and 68 ± 7 mM respectively. The transamination process of α-ketoglutarate was not affected by the presence of γ-vinyl GABA, whereas, taurine was a noncompetitive inhibitor of GABA-T when α-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 α-ketoglutarate respectively.
AB - γ-Aminobutyric acid transaminase (GABA-T, EC 2.6.1.19) is a pyridoxal phosphate (PLP) dependent enzyme that catalyzes the degradation of γ-aminobutyric acid. The kinetics of this reaction are studied in vitro, both in the absence, and in the presence of two inhibitors: γ-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 γ-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 γ-vinyl GABA and taurine were found to be 26 ± 3 mM and 68 ± 7 mM respectively. The transamination process of α-ketoglutarate was not affected by the presence of γ-vinyl GABA, whereas, taurine was a noncompetitive inhibitor of GABA-T when α-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 α-ketoglutarate respectively.
KW - Inhibitors
KW - Kinetics
KW - Taurine (ethylamine-2-sulfonic acid)
KW - γ-aminobutyric acid transaminase (GABA-T)
KW - γ-vinyl GABA (4-aminohex-5-enoic acid)
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U2 - 10.1080/1475636031000118428
DO - 10.1080/1475636031000118428
M3 - Article
C2 - 14567543
AN - SCOPUS:0041695624
SN - 1475-6366
VL - 18
SP - 297
EP - 301
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 4
ER -