Document Detail


Kinetic studies on the inhibition of GABA-T by gamma-vinyl GABA and taurine.
MedLine Citation:
PMID:  14567543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Saba A J Sulaiman; Fakhr Eldin O Suliman; Samira Barghouthi
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of enzyme inhibition and medicinal chemistry     Volume:  18     ISSN:  1475-6366     ISO Abbreviation:  J Enzyme Inhib Med Chem     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-10-21     Completed Date:  2004-05-03     Revised Date:  2007-03-21    
Medline Journal Info:
Nlm Unique ID:  101150203     Medline TA:  J Enzyme Inhib Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  297-301     Citation Subset:  IM    
Affiliation:
Sultan Qaboos University, Department of Chemistry, College of Science, Box 36, Al-Khod 123, Sultanate of Oman.
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MeSH Terms
Descriptor/Qualifier:
4-Aminobutyrate Transaminase / drug effects,  metabolism*
Enzyme Inhibitors / pharmacology*
Kinetics
Taurine / pharmacology*
Vigabatrin / pharmacology*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 107-35-7/Taurine; 60643-86-9/Vigabatrin; EC 2.6.1.19/4-Aminobutyrate Transaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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