CHOLINE DERIVATIVES AND SODIUM-FLUORIDE PROTECT ACETYLCHOLINESTERASE AGAINST IRREVERSIBLE INHIBITION AND AGING BY DFP AND PARAOXON

A light addressable potentiometric sensor was used to measure acetylch olinesterase (AChE) activity in order to evaluate the protective effec ts of quaternary compounds and NaF against enzyme phosphorylation and aging by two organophosphates. The use of the immobilized AChE made po ssible the quick removal of reagents (i.e., organophosphate, 2-pralido xime, and protectant), thereby permitting accurate determination of AC hE activity before and after phosphorylation and aging. Paraoxon was 1 5-fold more potent in inhibiting AChE than DFP, while the percent agin g following phosphorylation by diisopropylfluorophosphate (DFF) was mu ch higher. Sodium fluoride (NaF), the most effective protectant agains t phosphorylation and aging, and the quaternary ammonium compounds red uced significantly AChE inhibition by DFP and paraoxon, to similar deg rees. Even though the percent AChE activity that was lost to aging was reduced by these agents, aging as a percent of phosphorylated AChE wa s not reduced. Thus, their major effect was in reducing the percent AC hE phosphorylation, which consequently resulted in reduction of total aged AChE. The finding that quaternary ammonium compounds protect agai nst phosphorylation is consonant with the proposed presence of the act ive site of AChE in an aromatic gorge.