Influence of stereoisomers of 4-fluoroglutamate on rat brain glutamate decarboxylase

Inhibition of rat brain glutamate decarboxylase (GAD, EC 4.1.1.15) by indiv idual stereoisomers of 4-fluoroglutamate (4-F-Glu) and 2-fluoro-4-aminobuty rate (2-F-GABA) was studied. All stereoisomers of 4-F-Glu inhibited decarbo xylation 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 wit h 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. K-i values ran ged 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 reversi ble as shown by dialysis except for a small amount in the case of the D-ery thro isomer. The inhibition was independent of external pyridoxal-5'-phosph ate added. No inhibition of rat brain GAD was found with 2-fluoro-4-aminobu tyrate stereoisomers.