D-and L-stereoisomers of allylglycine: convulsive action and inhibition of brain L-glutamate decarboxylase.

Abstract

Abstract—DL‐Allylglycine was resolved into the L‐ and D‐stereoisomers using hog kidney acylase. Both isomers were active as convulsants after administration to mice. The dose of D‐allylglycine required to induce convulsions was greater than that of the L‐isomer. Studies on the concentration of the two isomers in brain suggest that the lower effectiveness of D‐allylglycine is partially due to its slower penetration into the brain through the blood‐brain barrier.Both isomers of allylglycine inhibited brain glutamate decarboxylase in vitro to approximately the same extent, however, in vivo L‐allylglycine inhibited the enzyme more strongly than the D isomer. Concentrations of allylglycine which caused a significant inhibition of L‐glutamate decarboxylase in vivo were ineffective in inhibiting the enzyme in vitro. Oxidation products derived from L‐ or D‐allylglycine by the action of either L‐ or D‐amino acid oxidase caused an almost complete inhibition of the enzyme in vitro. It is suggested that a common intermediate derived from the two isomers (possibly 2‐keto‐4‐pentenoic acid) is responsible for the in vivo inhibition of L‐glutamate decarboxylase and possibly also for the induction of convulsions.