Studies of the metabolism of parathion with an apparently homogeneous preparation of rabbit liver cytochrome P-450.
The metabolism of parathion has been examined by use of a reconstituted mixed-function oxidase enzyme system isolated from the livers of phenobarbital-pretreated rabbits. The cytochrome P-450 used in these studies was apparently homogeneous as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by assay of the preparation for contaminating microsomal enzymes and enzyme activity. These studies revealed that the apparently homogeneous preparation of cytochrome P-450, in the presence of the appropriate cofactors, can catalyze the conversions of parathion to both paraoxon and diethyl phosphorothioic acid. The present studies have also shown that parathion is metabolized by the reconstituted mixed-function oxidase enzyme system to diethyl phosphoric acid, a product which, in previous studies with intact liver microsomes, had been thought to arise exclusively from the hydrolysis of paraoxon by a microsomal esterase(s). The available data suggest that all three of the products of the metabolism of parathion by the reconstituted mixed-function oxidase enzyme system, namely, paraoxon, diethyl phosphorothioic acid, and diethyl phosphoric acid, are formed nonenzymatically by breakdown by different pathways of a common enzymatically formed intermediate. This common intermediate is thought to be the sulfine derivative of parathion formed in the mixed-function oxidase-catalyzed addition of an oxygen atom to one of the unshared electron pairs of the thiono-sulfur atom.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D007700:Kinetics; D008055:Lipids / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000302:isolation & purification / Q000378:metabolism; D010261:Paraoxon; D010278:Parathion / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits
D008055:Lipids; D003840:Deoxycholic Acid; D010278:Parathion; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D010261:Paraoxon; D010634:Phenobarbital