COMPARISON OF METABOLISM OF PARATHION BY A RAT-LIVER RECONSTITUTED MIXED-FUNCTION OXIDASE ENZYME-SYSTEM AND BY A SYSTEM CONTAINING CUMENE HYDROPEROXIDE AND PURIFIED RAT-LIVER CYTOCHROME-P-450

Abstract

The metabolism of parathion by a reconstituted mixed-function oxidase enzyme system (rat liver cytochrome P-450, NADPH-cytochrome c reductase, dilauroyl phosphatidylcholine, deoxycholate and NADPH) or a cumene hydroperoxide system (cytochrome P-450, dilauroyl phosphatidylcholine and cumene hydroperoxide) were compared. The products formed on incubation of parathion with both systems were paraoxon, diethyl phosphorothioic acid, diethyl phosphoric acid, p-nitrophenol and atomic S. The apparent Km values for parathion for formation of paraoxon and diethyl phosphorothioic acid with the cumene hydroperoxide system were 55 and 39 .times. 10-6 M, respectively. These Km values are not significantly different. When the reconstituted system was used, apparent Km values of 2.8 .times. 10-6 M for formation of paraoxon and 3.9 .times. 10-6 M for formation of diethyl phosphorothioic acid and diethyl phosphoric acid were determined. These Km values are also not significantly different. The covalent binding of the S atom, released in the metabolism of parathion to paraoxon, to the protens of the reconstituted system and to cytochrome P-450 of the cumene hydroperoxide system was also examined. With both the reconstituted system and the cumene hydroperoxide system, approximately 65% of the S released became bound to the proteins of these enzyme systems. The binding of the S atom resulted in a progressive inhibition of the metabolism of parathion by these 2 systems.