Elfaki Imadeldin, Mir Rashid, Almutairi Fahad M, Duhier Faisel M Abu
Department of Biochemistry, Faculty of Science, University of Tabuk, Kingdom of Saudi Arabia. Email:
Asian Pac J Cancer Prev. 2018 Aug 24;19(8):2057-2070. doi: 10.22034/APJCP.2018.19.8.2057.
Cytochromes P450s (CYPs) constitute a superfamily of enzymes that catalyze the metabolism of drugs and other substances. Endogenous substrates of CYPs include eicosanoids, estradiol, arachidonic acids, cholesterol, vitamin D and neurotransmitters. Exogenous substrates of CYPs include the polycyclic aromatic hydrocarbons and about 80% of currently used drugs. Some isoforms can activate procarcinogens to ultimate carcinogens. Genetic polymorphisms of CYPs may affect the enzyme catalytic activity and have been reported among different populations to be associated with various diseases and adverse drug reactions. With regard of drug metabolism, phenotypes for CYP polymorphism range from ultrarapid to poor metabolizers. In this review, we discuss some of the most clinically important CYPs isoforms (CYP2D6, CYP2A6, CYP2C19, CYP2C9, CYP1B1 and CYP1A2) with respect to gene polymorphisms and drug metabolism. Moreover, we review the role of CYPs in renal, lung, breast and prostate cancers and also discuss their significance for atherosclerosis and type 2 diabetes mellitus.
细胞色素P450（CYPs）构成了一个酶超家族，可催化药物和其他物质的代谢。CYPs的内源性底物包括类二十烷酸、雌二醇、花生四烯酸、胆固醇、维生素D和神经递质。CYPs的外源性底物包括多环芳烃和约80%的当前使用药物。一些同工型可将前致癌物激活为最终致癌物。CYPs的基因多态性可能影响酶的催化活性，并且在不同人群中已有报道称其与各种疾病和药物不良反应相关。关于药物代谢，CYP多态性的表型范围从超快速代谢者到慢代谢者。在本综述中，我们讨论了一些临床上最重要的CYPs同工型（CYP2D6、CYP2A6、CYP2C19、CYP2C9、CYP1B1和CYP1A2）在基因多态性和药物代谢方面的情况。此外，我们综述了CYPs在肾癌、肺癌、乳腺癌和前列腺癌中的作用，并讨论了它们在动脉粥样硬化和2型糖尿病中的意义。
