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Oxygen and Xenobiotic Reductase Activities of Cytochrome P450

 

作者: GoeptarArnold R.,   ScheerensHeleen,   VermeulenNico P. E.,  

 

期刊: Critical Reviews in Toxicology  (Taylor Available online 1995)
卷期: Volume 25, issue 1  

页码: 25-65

 

ISSN:1040-8444

 

年代: 1995

 

DOI:10.3109/10408449509089886

 

出版商: Taylor&Francis

 

关键词: cytochrome P450;reductive activity;uncoupling;free radicals;oxygen reductase;xenobiotic reductase

 

数据来源: Taylor

 

摘要:

AbstractThe 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 (O−2) most likely by autooxidation of a P450 ferric-dioxyanion complex. The formation of reactive oxygen species (O−2, 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.

 

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