The inhibition of hydrolytic enzymes by organophosphorus compounds.

It has been shown that several hydrolytic enzymes with different specificities undergo similar reactions with diisopropyl phosphorofluoridate (1) and other related toxic organophosphorus compounds (2). These conclusions were based on kinetic studies, particularly the influence of pH on the rates of reaction, and on inhibition characteristics. Reactions of this type have provided a unique method of attacking the problem of the nature of the active site of enzymes, supplementing the approaches via substrate specificity studies and the structural analysis of the enzyme protein itself (3-5). Although the physiological response of animals intoxicated with organophosphorus esters has led to the recognition of the anticholinergic action of these substances, there is evidence that reaction with other enzymes may influence toxicity and a more precise understanding of the specificity of action of various organophosphorus compounds is desirable (6). The present report describes the effect of a number of organophosphorus compounds on seven hydrolytic enzymes, comprising three e&erases (acetylcholinesterase, plasma cholinesterase, and wheat germ esterase), and four proteolytic enzymes (chymotrypsin, trypsin, plasmin, and thrombin).