ROLE OF LIPOXYGENASE IN XENOBIOTIC OXIDATION - PARATHION METABOLISM CATALYZED BY HIGHLY PURIFIED SOYBEAN LIPOXYGENASE

Earlier studies from this laboratory demonstrated that lipoxygenase catalyzes oxidation of a number of xenobiotics. This report presents data on the desulfuration and dearylation of parathion catalyzed by purified soybean lipoxygenase in the presence of linoleic acid. The formation of paraoxon was estimated from in vitro inhibition of acetylcholinesterse (electric eel) and further confirmed by using [14C]parathion. The metabolites paraoxon and p-nitrophenol were separated on thin layer chromatography and quantified by radiometry. The maximal rate of parathion metabolism occurred in the presence of 1.0 mM linoleic acid, 25.0 μM parathion, 20.0 nM enzyme at pH 8.0. The rate of desulfuration and dearylation reactions were dependent on incubation time, pH, linoleic acid, parathion, and enzyme concentration. Lipoxygenase inhibitors, like nor-dihydroguaiaretic acid and phenidone, significantly blocked the desulfuration and dearylation reactions. The turnover numbers (nmol product/min/nmol enzyme) were found to be 3.0 and 5.5 for paraoxon and p-nitrophenol, respectively. The rate of lipoxygenase-catalyzed parathion bioactivation was 3-20 times greater as compared to purified mammalian cytochrome P-450. © 1991.