4-(Oxoalkyl)-substituted GABA analogues as inactivators and substrates of GABA aminotransferase.
On the basis of the mechanism of inactivation of gamma-aminobutyric acid (GABA) aminotransferase by gamma-ethynyl GABA that was reported recently (Burke and Silverman, manuscript submitted), three 4-(oxoalkyl)-substituted GABA analogues, 4-amino-5-oxohexanoic acid (7), 4-amino-5-oxopentanoic acid (8), and 4-amino-6-oxohexanoic acid (9) were synthesized and tested as inactivators. Only 8 was an inactivator of the enzyme. A mechanism for the inactivation by 8 is proposed as well as rationalizations for the lack of inactivation by 7 and 9.
Burke
J R
JR
Department of Chemistry, Northwestern University, Evanston, Illinois 60208-3113.
Silverman
R B
RB
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000478:Alkylation; D000818:Animals; D001921:Brain / Q000201:enzymology; D007700:Kinetics; D013379:Substrate Specificity; D013552:Swine; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase