Inhibition of acetylcholinesterase by dibenamine and dibenzyline

Abstract

Abstract Dibenamine and dibenzyline are irreversible inhibitors of acetylcholinesterase (AChE). Kinetic studies show that at pH 9.5 a fast reaction occurs between a group on the enzyme with pKa 9.1 and the ethyleniminium ion derived from the inhibitor. Either the ε-amino-group of a lysine residue is alkylated or else a lysine residue catalyses the alkylation of a non-ionisable group (e.g. hydroxyl). At pH 6.5 there is a slow reaction between a carboxyl anion on the enzyme and the ethyleniminium ion. Studies of the alkylation reactions in the presence of the reversible competitive inhibitor of the enzyme, tetramethylammonium ion, show that alkylation occurs at some distance from the anionic site and probably on the borders of the active site.