A kinetic model for the action of the enzyme activated irreversible inhibitor 4-amino-5-hexynoic acid in vivo.

The extent of inactivation of three aminotransferases by the enzyme activated inhibitor 4-amino-hex-5-ynoate (acetylenic-GABA) increased with increasing dose in an exponential fashion. Theoretical treatment of the data allowed an estimate of the effective concentration of the drug at its site of action to be made and it was apparent that any rises in substrate concentration produced by the inactivation did not protect the enzyme significantly. Altered diet produced distinct changes in the extent of inactivation of aspartate aminotransferase, but not with ornithine aminotransferase. Cysteine sulphinate, a substrate only of aspartate aminotransferase, also affected the inactivation of ornithine aminotransferase, suggesting that secondary metabolic effects were responsible.