Role of cytochrome P-450 in hydrocarbon formation from xenobiotic and lipid hydroperoxides.

Cytochrome P-450 has recently been found to catalyze the reductive cleavage of both xenobiotic hydroperoxides and biologically occurring lipid hydroperoxides. In a reconstituted enzyme system containing phenobarbital-inducible P-450 form 2, NADPH-cytochrome P-450 reductase, and NADPH, the corresponding alcohols are not produced, but instead carbonyl compounds and hydrocarbons. In the following equation for the reaction, X represents any of a variety of alkyl groups and R and R' are either hydrogen or alkyl groups, of which only methyl has been studied so far: XRR'C-OOH + NADPH + H+----XRCO + R'H + H2O + NADP+ The products derived from cumyl, alpha-methylbenzyl, benzyl, and t-butyl hydroperoxides as well as 13-hydroperoxy-9,11-octadecadienoic acid indicate that the reaction involves stepwise one-electron transfer, resulting in homolysis of the peroxide oxygen-oxygen bond. The alkoxy radical thus generated undergoes beta-scission to yield the carbonyl compound and an alkyl radical that is reduced to the alkane. As predicted by this radical mechanism, when the reductive cleavage of cumyl hydroperoxide was carried out in D2O, deuteromethane was formed.