AGING AND SPONTANEOUS REACTIVATION OF HUMAN PLASMA CHOLINESTERASE ACTIVITY AFTER INHIBITION BY ORGANOPHOSPHORUS PESTICIDES

The in vitro rates of aging and spontaneous reactivation of human plas ma cholinesterase (ChE) after inhibition by several organophosphorus p esticides (OPs) have been studied. After inhibition by OP the enzyme c an undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the en zyme, The rates of these two reactions depend on the nature of the pho sphoryl group of the OP bound to the active site of ChE. Most OPs regi stered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom, Reaction rate constants for aging and spontaneou s reactivation are reported, Dimethoxy OPs cause half-lives of aging i n human plasma ChE of approximately 6 hours and 23 hours at 37-degrees -C and 22-degrees-C respectively; for diethoxy OPs the values are 12 h ours and 39 hours. Reappearance of enzyme activity, after removal of O P, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours a nd 15 hours at 37-degrees-C and 22-degrees-C. These effects, both in v ivo and ex vivo, may have relevance in developing a monitoring strateg y for dimethoxy OPs using plasma ChE measurements. Inhibition by dieth oxy OPs spontaneously reactivates very slowly, even at 37-degrees-C, a nd would not practically influence the measured inhibition. No spontan eous reactivation was detected in human plasma ChE inhibited by the me thoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylam ino substituted OP (crufomate) during 45 hours incubation at 37-degree s-C,