Influence of stereoisomers of 4-fluoroglutamate on rat brain glutamate decarboxylase.
Inhibition of rat brain glutamate decarboxylase (GAD, EC 4.1.1.15) by individual stereoisomers of 4-fluoroglutamate (4-F-Glu) and 2-fluoro-4-aminobutyrate (2-F-GABA) was studied. All stereoisomers of 4-F-Glu inhibited decarboxylation of L-glutamate catalysed by the enzyme preparation. At 1 x 10(-2) M concentration, the most potent inhibitor of GAD was D-erythro-4-F-Glu with about 70% inhibition in the presence of 1.23 x 10(-2)M L-glutamate. The inhibition by all stereoisomers was of the competitive type. Ki values ranged from 2 x 10(-3)M for the D-erythro isomer to 1.1 x 10(-2)M for the D-threo and L-erythro isomers. The influence of all stereoisomers was reversible as shown by dialysis except for a small amount in the case of the D-erythro isomer. The inhibition was independent of external pyridoxal-5'-phosphate added. No inhibition of rat brain GAD was found with 2-fluoro-4-aminobutyrate stereoisomers.
Drsata
J
J
Faculty of Pharmacy in Hradec Králové, Department of Biochemical Sciences, Charles University in Prague, Czech Republic.
Netopilová
M
M
Tolman
V
V
D000818:Animals; D001921:Brain / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D005971:Glutamates / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005971:Glutamates; C038473:4-fluoroglutamic acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase