MICROSOMAL LIPID-PEROXIDATION - THE ROLE OF NADPH-CYTOCHROME-P450 REDUCTASE AND CYTOCHROME-P450

The role of NADPH - cytochrome P450 reductase and cytochrome P450 in NADPH- and ADP - Fe3+-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 - Fe3+-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 O2 reduction. The first electron is used for reduction of ADP - Fe3+ and subsequent addition of O2 to the perferryl radical (ADP - Fe3+-O2-), which then extracts an H atom from a polyunsaturated lipid (LH) giving rise to a free radical (LH·) that reacts with O2 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 - Fe2+ or by the superoxide radical as generated through redox cycling of a quinone such as menadione. © 1990.