Published 1989 | Version v1
Book

Inactivation of γ-aminobutyric acid aminotransferase by γ-ethynyl- and γ-vinyl GABA

  • 1. Northwestern Univ., Evanston, IL (USA)

Description

γ-Ethynyl- and γ-vinyl GABA (vigabatrin) are anticonvulsant agents that have been shown to be mechanism-based inactivators of γ-aminobutyric acid aminotransferase (GABA-T). The inactivation mechanisms of these compounds have been investigated. Inactivation of GABA-T by [3H]γ-ethynyl GABA led to the incorporation of 1.0 equiv of 3H into the enzyme which is not released by enzyme denaturation. Inactivation by γ-ethynyl GABA of GABA-T reconstituted with [3H]PLP followed by denaturation resulted in release of 3H as PLP. Eight different possible adducts are consistent with that result. Experiments have been carried out to differentiate these possibilities. Similar studies have been carried out with γ-vinyl GABA. Inactivation by [14C]γ-vinyl GABA resulted in the incorporation of 1.0 equiv of 14C per active site. Unlike the case with γ-ethynyl GABA, γ-vinyl GABA inactivation of GABA-T reconstituted with [3H]PLP followed by denaturation resulted in release of 3H as PMP

Additional details

Publishing Information

Publisher
American Chemical Society.
Imprint Place
Washington, DC (USA)
Imprint Title
The 1989 international chemical congress of Pacific Basin Societies: Abstracts of papers, Parts I and II
Imprint Pagination
1700 p.
Journal Page Range
p. 475, Paper BIOS 331.

Conference

Title
International chemical congress of Pacific Basin Societies (PACIFICHEM '89).
Dates
17-22 Dec 1989.
Place
Honolulu, HI (USA).

Optional Information

Secondary number(s)
CONF-891206--.