Reactivation and Aging of α-Chymotrypsin Inhibited by the Chiral Isomers of EPN-oxon and Saligenin Cyclic Phosphoryl Compounds

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Abstract
Reactivation and aging of α-chymotrypsin inhibited by organophosphorus compounds including delayed-neurotoxic and non-neurotoxic agents were studied. Delayed-neurotoxic o-tolyloxy and phenyl analogs of salioxon, and (—)-EPN-oxon reacted stoichiometrically with α-chymotrypsin to inhibit its esterase activity, whereas non-neurotoxic salioxon and (+)-EPN-oxon inhibited the enzyme less specifically as compared with the former three compounds. The enzyme inhibited by EPN-oxon isomers was slowly reactivated and completely dephosphorylated with about 300 molar equivalents of PAM to regenerate the active enzyme. On the other hand, the enzyme inhibited by saligenin cyclic phosphoryl compounds was not reactivated even by the action of PAM. The phosphorylated enzyme underwent rapid cleavage of the P-O-salicyl linkage in processes referred to as aging, yielding an inactive enzyme with an ionized acidic phosphorus group. There seems to be no differences in reactivation and aging processes of the inhibited α-chymotrypsin between delayed-neurotoxic and non-neurotoxic compounds.