Species Differences in Serum Paraoxonase Correlate with Sensitivity to Paraoxon Toxicity

Abstract

Paraoxon (diethyl-p-nitrophenylphosphate) is the active metabolite of parathion (diethyl-p-nitrophenylphosphorothioate), a widely used organo-phosphorus insecticide. After activation of parathion by the cytochrome P450 system, the paraoxon is hydrolyzed by a serum enzyme, paraoxonase (EC 3.1.1.2), to generate p-nitrophenol and diethylphosphoric acid (Zech and Zurcher, 1974). Measurement of paraoxonase activity in sera from human subjects of European origin (i.e. Caucasian) has revealed a bimodal or trimodal distribution (Mueller et al. 1983; Eckerson et al. 1983). Cn the basis of enzymatic tests, humans can be divided into three serum paraoxonase phenotypes: A (low activity), AB (intermediate activity), and B (high activity), with about 50% of the studied populations of European origin displaying low activity (Eckerson et al. 1983).