Sevanian A, Nordenbrand K, Kim E, Ernster L, Hochstein P
Institute for Toxicology, University of Southern California, Los Angeles 90033.
Free Radic Biol Med. 1990;8(2):145-52. doi: 10.1016/0891-5849(90)90087-y.
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.
通过使用从大鼠全肝磷脂或牛磷脂酰胆碱与磷脂酰乙醇胺混合物（PC/PE脂质体）制备的纯化酶和脂质体，研究了NADPH - 细胞色素P450还原酶和细胞色素P450在NADPH和ADP - Fe³⁺依赖性脂质过氧化中的作用。结果表明，NADPH和ADP - Fe³⁺依赖性脂质过氧化涉及NADPH - 细胞色素P450还原酶和细胞色素P450。正如细胞色素P450相关的单加氧反应一样，这些酶在脂质过氧化中的作用可能是为O₂还原提供两个电子。第一个电子用于还原ADP - Fe³⁺，随后O₂添加到过氧铁自由基（ADP - Fe³⁺ - O₂⁻）上，然后该自由基从多不饱和脂质（LH）中提取一个H原子，产生一个自由基（LH·），该自由基与O₂反应生成过氧化物自由基（LOO·）。然后第二个电子用于将LOO·还原为脂质氢过氧化物（LOOH）。在后一种情况下，还原型细胞色素P450可以被EDTA - Fe²⁺或通过醌（如甲萘醌）的氧化还原循环产生的超氧自由基所替代。
