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细胞色素P450多态性——分子、代谢及药物遗传学方面。I. 细胞色素P450单加氧酶的活性机制。

Cytochrome P450 polymorphism--molecular, metabolic and pharmacogenetic aspects. I. Mechanisms of activity of cytochrome P450 monooxygenases.

作者信息

Pachecka Jan, Tomaszewski Piotr, Kubiak-Tomaszewska Grazyna

机构信息

Department of Biochemistry and Clinical Chemistry, Pharmaceutical Faculty, Medical University of Warsaw, Warsaw, Poland.

出版信息

Acta Pol Pharm. 2008 May-Jun;65(3):303-6.

PMID:18646549
Abstract

Cytochrome P450, initially perceived as a type of cell pigment, was soon identified as a hemoprotein with an enzymatic activity characteristic for monooxygenases with an affinity for differentiated endo- or exogenous substrates, including drugs. So far in the human organism 58 CYP isoenzymes belonging to 18 families have been described. Most from the CYP monooxygenases superfamily turned out to be integral elements of hepatocytic reticular monooxygenase complexes which also contain NADPH-dependent cytochrome P450 reductase (CPR). Later investigations indicated the possibility of the participation in electron transport for reticular CYP isoenzymes, alternative NADH-dependent reticular system composed of cytochrome b5 reductase (CBR) and cytochrome b5. The demonstration of the activity of some CYP superfamily isoenzymes not only in hepatocytes but also in many other cells of the human organism, numerous plant and animal tissues and even in cells of fungi, protists and prokaryotes has contributed to the significantly increased understanding of the role of CYP in biological systems. In addition, some CYP isoenzymes were found to be characteristic for the inner mitochondrial membrane monooxygenase complexes which contain NADPH-dependent adrenodoxin reductase (AR) and adrenodoxin (Ad), which is identical with ferredoxin-1 (Fd-1) and hepatoredoxin (Hd).

摘要

细胞色素P450最初被认为是一种细胞色素,很快被鉴定为一种血红素蛋白,具有单加氧酶的酶活性特征,对包括药物在内的内源性或外源性底物具有亲和力。迄今为止,在人体中已描述了属于18个家族的58种CYP同工酶。事实证明,CYP单加氧酶超家族中的大多数是肝细胞网状单加氧酶复合物的组成部分,该复合物还含有NADPH依赖性细胞色素P450还原酶(CPR)。后来的研究表明,由细胞色素b5还原酶(CBR)和细胞色素b5组成的替代性NADH依赖性网状系统可能参与网状CYP同工酶的电子传递。一些CYP超家族同工酶不仅在肝细胞中,而且在人体的许多其他细胞、众多动植物组织甚至真菌、原生生物和原核生物的细胞中都具有活性,这大大增进了人们对CYP在生物系统中作用的理解。此外,还发现一些CYP同工酶是线粒体内膜单加氧酶复合物的特征性成分,该复合物含有NADPH依赖性肾上腺皮质铁氧还蛋白还原酶(AR)和肾上腺皮质铁氧还蛋白(Ad),后者与铁氧还蛋白-1(Fd-1)和肝铁氧还蛋白(Hd)相同。

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