Abstract:

Several alkylating agents (bromobenzylcyanide, chloroacetophenon, and xylyl bromide) were found to inhibit cholisterase from human plasma. Less reactive alkylating compounds such as bromoacetone, chloroacetate, and iodoacetate did not inhibit the enzyme. Chloropicrin, which is a powerful oxidizing agent, was not found to inhibit either. Several mercaptide-forming agents, like p-chloromercuribenzoic acid, diphenylaminechloroarsine, and ethyl-dichloroarsine, were effective inhibitors. w-Chloroacetophenon was found to be an instantaneous and noncompetitive inhibitor. The inhibition was reversible by dilution or dialysis. The degree of inhibition was higher in an aqueous medium that when a less polar solvent was used. These findings suggest that a sulfhydryl group is not involved during the inhibition of cholinesterase by alkylating agents. The possibility of a reaction on the histidine or methionine groups of the enzyme is discussed. The inhibition also was dependent on the substrate employed during the activity assay. The order of percentage of inhibition was found to be acetylcholine > butyrylcholine > benzoylcholine. These data are used to offer an interpretation for some aspects of the lachrymatory action of these agents. © 1968.