Formation of P450 · P450 complexes and their effect on P450 function.
Formation of P450 · P450 complexes and their effect on P450 function.
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DOI：
10.1016/j.pharmthera.2011.11.009
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发表时间：
2012-03
影响因子：
13.5
通讯作者：
Backes, Wayne L.
中科院分区：
文献类型：
--
作者：
Reed, James R.;Backes, Wayne L.
细胞色素P450 （P450）是一种膜结合酶，可催化多种外源和内源化合物的单氧作用。负责外源化合物代谢的p450一般定位于肝、肺和小肠的内质网。P450酶不是单独作用，而是需要与其他电子转移蛋白如nadph -细胞色素P450还原酶（CPR）和细胞色素b5相互作用。由于P450与这些和其他内质网蛋白一起定位于内质网，因此蛋白质-蛋白质相互作用可能会影响P450的功能。越来越多的证据表明，P450酶在内质网中形成复合物，有力地支持了P450•P450复合物的形成可以显著影响其功能。我们的目标是回顾支持P450•P450复合物形成的研究，它们的特异性，以及如何影响药物代谢。这篇综述描述了p450相互作用的潜在机制，并提供了支持每种可能机制的证据。此外，对异质和同源P450复合物形成的证据进行了综述。最后，总结了P450复合物在溶液和膜中形成的直接物理证据，并讨论了P450功能相互作用对药物代谢的潜在影响，指导未来研究的问题。
Cytochromes P450 (P450) are membrane-bound enzymes that catalyze the monooxygenation of a diverse array of xenobiotic and endogenous compounds. The P450s responsible for foreign compound metabolism generally are localized in the endoplasmic reticulum of the liver, lung and small intestine. P450 enzymes do not act alone but require an interaction with other electron transfer proteins such as NADPH-cytochrome P450 reductase (CPR) and cytochrome b5. Because P450s are localized in the endoplasmic reticulum with these and other ER-resident proteins, there is a potential for protein-protein interactions to influence P450 function. There has been increasing evidence that P450 enzymes form complexes in the ER, with compelling support that formation of P450•P450 complexes can significantly influence their function. Our goal is to review the research supporting the formation of P450•P450 complexes, their specificity, and how drug metabolism may be affected. This review describes the potential mechanisms by which P450s may interact, and provides evidence to support each of the possible mechanisms. Additionally, evidence for the formation of both heteromeric and homomeric P450 complexes are reviewed. Finally, direct physical evidence for P450 complex formation in solution and in membranes is summarized, and questions directing the future research of functional P450 interactions are discussed with respect to their potential impact on drug metabolism.
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影响因子：
2.9
作者：
Backes, WL;Batie, CJ;Cawley, GF
通讯作者：
Cawley, GF
影响因子：
3.9
作者：
Hu, Gang;Johnson, Eric F.;Kemper, Byron
通讯作者：
Kemper, Byron
影响因子：
9.8
作者：
ESTABROOK, RW;FRANKLIN, MR;HILDEBRANDT, AG
通讯作者：
HILDEBRANDT, AG
DOI：
10.1111/j.1432-1033.1985.tb09001.x
发表时间：
1985-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DAVYDOV, DR;KARYAKIN, AV;ARCHAKOV, AI
通讯作者：
ARCHAKOV, AI
影响因子：
1.8
作者：
GREINERT, R;FINCH, SAE;STIER, A
通讯作者：
STIER, A