Stereochemistry of reactions catalysed by mammalian-brain L-glutamate 1-carboxy-lyase and 4-aminobutyrate: 2-oxoglutarate aminotransferase.

Deamination of 4-aminobutyrate by mammalian or bacterial 4-aminobutyrate aminotransferases involves the abstraction of the pro-S hydrogen on C-4 of 4-aminobutyrate. Decarboxylation of L-glutamate by rat brain glutamate decarboxylase occurs with retention of configuration. Inhibition of this enzyme by (S)-4-aminohex-5-ynoic acid involves the abstraction of the proton at C-4 of the inhibitor. On the basis of this finding, we postulate the existence of an abnormal reaction of glutamate decarboxylase in which the proton at C-4 of (S)-4-aminohex-5-ynoic acid is removed in a manner similar to the one which normally occurs in enzymatic transaminations of L-amino acids. This reaction is presumably facilitated by the acetylenic group adjacent to the eliminated proton.