Goeptar A R, Scheerens H, Vermeulen N P
Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, The Netherlands.
Crit Rev Toxicol. 1995;25(1):25-65. doi: 10.3109/10408449509089886.
The oxygen reductase and xenobiotic reductase activities of cytochrome P450 (P450) are reviewed. During the oxygen reductase activity of P450, molecular oxygen is reduced to superoxide anion radicals (O2-.) most likely by autooxidation of a P450 ferric-dioxyanion complex. The formation of reactive oxygen species (O2-., hydrogen peroxide, and, notably, hydroxyl free radicals) presents a potential toxication pathway, particularly when effective means of detoxication are lacking. Under anaerobic conditions, P450 may also be involved in the reduction of xenobiotics. During the xenobiotic reductase activity of P450, xenobiotics are reduced by the ferrous xenobiotic complex. After xenobiotic reduction by P450, xenobiotic free radicals are formed that are often capable of reacting directly with tissue macromolecules. Unfortunately, the compounds that are reductively activated by P450 have little structural similarity. The precise molecular mechanism underlying the xenobiotic reductase activity of P450 is, therefore, not yet fully understood. Moreover, description of the molecular mechanisms of xenobiotic and oxygen reduction reactions by P450 is limited by the lack of knowledge of the three-dimensional (3D) structure of the mammalian P450 proteins.
本文综述了细胞色素P450（P450）的氧还原酶和外源性物质还原酶活性。在P450的氧还原酶活性过程中，分子氧很可能通过P450铁二氧阴离子复合物的自氧化作用被还原为超氧阴离子自由基（O2-.）。活性氧物质（O2-.、过氧化氢，尤其是羟基自由基）的形成是一条潜在的中毒途径，特别是在缺乏有效解毒手段时。在厌氧条件下，P450也可能参与外源性物质的还原。在P450的外源性物质还原酶活性过程中，外源性物质被亚铁外源性物质复合物还原。P450对外源性物质进行还原后，会形成外源性自由基，这些自由基通常能够直接与组织大分子发生反应。遗憾的是，被P450还原激活的化合物在结构上几乎没有相似性。因此，P450外源性物质还原酶活性背后的确切分子机制尚未完全明确。此外，由于缺乏对哺乳动物P450蛋白三维（3D）结构的了解，对P450介导的外源性物质和氧还原反应分子机制的描述也受到限制。
