In vitro and in vivo effects on brain GABA metabolism of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based inactivator of gamma-aminobutyric acid transaminase.
The effects of intraperitoneal administration of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based covalent inactivator of gamma-aminobutyric acid transaminase (GABA-T), on whole brain GABA metabolism in mice were investigated. A dose-dependent and time-dependent irreversible inactivation of GABA-T was observed with a concomitant increase in whole brain GABA levels. The compound exhibited no in vitro nor in vivo time-dependent inhibition of glutamate decarboxylase (GAD), alanine transaminase, or aspartate transaminase (Asp-T). It was, however, a potent competitive reversible inhibitor of GAD and a weak competitive inhibitor of Asp-T. The chloro analogue, (S)-4-amino-5-chloropentanoic acid, was ineffective.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010421:Pentanoic Acids / Q000494:pharmacology*; D000637:Transaminases / Q000037:antagonists & inhibitors*; D014631:Valerates / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D010421:Pentanoic Acids; D014631:Valerates; D005680:gamma-Aminobutyric Acid; C032606:4-amino-5-fluoropentanoic acid; D000637:Transaminases; D001219:Aspartate Aminotransferases; D000612:4-Aminobutyrate Transaminase; D000410:Alanine Transaminase; D005968:Glutamate Decarboxylase