Inactivation of γ-aminobutyric acid aminotransferase by γ-ethynyl- and γ-vinyl GABA
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).
INIS
- Country of Publication
- United States
- Country of Input or Organization
- United States
- INIS RN
- 22028758
- Subject category
- S60: APPLIED LIFE SCIENCES;
- Resource subtype / Literary indicator
- Conference
- Quality check status
- Yes
- Descriptors DEI
- AMINOBUTYRIC ACID; AMINOTRANSFERASES; ANTICONVULSANTS; BIOLOGICAL EFFECTS; CARBON 14 COMPOUNDS; ENZYME ACTIVITY; INHIBITION; PROTEIN DENATURATION; TRACER TECHNIQUES; TRITIUM COMPOUNDS;
- Descriptors DEC
- AMINO ACIDS; AUTONOMIC NERVOUS SYSTEM AGENT; CARBON COMPOUNDS; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM AGENTS; CENTRAL NERVOUS SYSTEM DEPRESS; DRUGS; ENZYMES; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; NEUROREGULATORS; NITROGEN TRANSFERASES; ORGANIC ACIDS; ORGANIC COMPOUNDS; TRANSFERASES;
Optional Information
- Secondary number(s)
- CONF-891206--.