Microsomal lipid peroxidation: The role of NADPH — Cytochrome P450 reductase and cytochrome P450

Abstract

The role of NADPH — cytochrome P450 reductase and cytochrome P450 in NADPH- and ADP — Fe 3+-dependent lipid peroxidation was investigated by using the purified enzymes and liposomes prepared from either total rat-liver phospholipids or a mixture of bovine phsphatidyl choline and phosphatidyl ethanolamine (PC/PE liposomes). The results suggest that NADPH- and ADP — Fe 3+-dependent lipid peroxidation involves both NADPH — cytochrome P450 reductase and cytochrome P450. Just as in the case of cytochrome P450-linked monooxygenations, the role of these enzymes in lipid peroxidation may be to provide two electrons for O 2 reduction. The first electron is used for reduction of ADP — Fe 3+ and subsequent addition of O 2 to the perferryl radical (ADP — Fe 3+-O 2 −), which then extracts an H atom from a polyunsaturated lipid (LH) giving rise to a free radical (LH·) that reacts with O 2 yielding a peroxide free radical (LOO·). The second electron is then used to reduce LOO· to the lipid hydroperoxide (LOOH). In the latter capacity, reduced cytochrome P450 can be replaced by EDTA — Fe 2+ or by the superoxide radical as generated through redox cycling of a quinone such as menadione.