Comparison of the 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.
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) have been compared. The products formed on incubation of parathion with both systems were paraoxon, diethyl phosphorothioic acid, diethyl phosphoric acid, p-nitrophenol, and atomic sulfur. The apparent KM values for parathion for formation of paraoxon and diethyl phosphorothioic acid with the cumene hydroperoxide system were 55 and 39 X 10(-6) M, respectively. These KM values are not significantly different. When the reconstituted system was used, apparent KM values of 2.8 x 10(-6) M for formation of paraoxon and 3.9 x 10(-6) M for The formation of diethyl phosphorothioic acid and diethyl phosphoric acid were determined. These KM values are also not significantly different. covalent binding of the sulfur atom, released in the metabolism of parathion to paraoxon, to the proteins 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 sulfur released became bound to the proteins of these enzyme systems. The binding of the sulfur atome resulted in a progressive inhibition of the metabolism of parathion by these two systems.
D000818:Animals; D001589:Benzphetamine / Q000378:metabolism; D001593:Benzyl Compounds / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010278:Parathion / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D013455:Sulfur / Q000378:metabolism; D013997:Time Factors
D001593:Benzyl Compounds; D010545:Peroxides; D010713:Phosphatidylcholines; D003840:Deoxycholic Acid; D001589:Benzphetamine; D010278:Parathion; D013455:Sulfur; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital