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 phosphatidyl 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.
Sevanian
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A
Institute for Toxicology, University of Southern California, Los Angeles 90033.
Nordenbrand
K
K
Kim
E
E
Ernster
L
L
Hochstein
P
P
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002417:Cattle; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004492:Edetic Acid / Q000378:metabolism; D005609:Free Radicals; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D005609:Free Radicals; D010743:Phospholipids; D000244:Adenosine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D004492:Edetic Acid; D007501:Iron; D009251:NADPH-Ferrihemoprotein Reductase; D001205:Ascorbic Acid