Wiśniewska Anita, Mazerska Zofia
Department of Pharmaceutical Technology and Biochemistry, Chemical Faculty, Gdańsk University of Technology, 11/12 Narutowicza St., 80-233 Gdańsk, Poland.
Postepy Biochem. 2009;55(3):259-71.
Cytochrome P450 enzymes (CYPs) belong to hemeproteins found in all living organisms. In eucaryotic cells they are responsible for biosynthesis and transformations of endogenic lipids as well as for the metabolism of xenobiotics, including therapeutic agents. C-Oxidation (hydroxylation, epoxydation, peroxydation), N-oxidation and S-oxidation as well as oxidative O-, S-, and N-dealkylation of substrates are catalysed by CYPs. These monooxygenation reactions sometimes result in dimerisation, isomerisation or cyclisation of the substrate. Human cytochrome P450 isoenzymes are described by 57 genes and products of their expression are different in specificity. For instance CYP51A1 is crucial for sterol biosynthesis, whereas CYP7A1, 7B1 and 39A1 take part in synthesis of bile acids and CYP46A1 in metabolism of cholesterol. Therapeutic agents are metabolised mainly by CYP3A4, 2D6, 2C9 and 2C19. In addition, CYP2E1 takes part in metabolism of ethyl alcohol and CYP1A1/2 in activation of carcinogens. Metabolism of xenobiotics seems to be the defence mechanism against toxic effects of strange chemicals, whereas, it is also the way of drug activation and detoxication.
细胞色素P450酶（CYPs）属于在所有生物中都能找到的血红素蛋白。在真核细胞中，它们负责内源性脂质的生物合成和转化以及包括治疗药物在内的外源性物质的代谢。CYPs催化底物的C-氧化（羟基化、环氧化、过氧化）、N-氧化和S-氧化以及氧化O-、S-和N-脱烷基反应。这些单加氧反应有时会导致底物的二聚化、异构化或环化。人类细胞色素P450同工酶由57个基因描述，其表达产物在特异性上有所不同。例如，CYP51A1对甾醇生物合成至关重要，而CYP7A1、7B1和39A1参与胆汁酸的合成，CYP46A1参与胆固醇的代谢。治疗药物主要由CYP3A4、2D6、2C9和2C19代谢。此外，CYP2E1参与乙醇的代谢，CYP1A1/2参与致癌物的激活。外源性物质的代谢似乎是抵御外来化学物质毒性作用的防御机制，然而，它也是药物激活和解毒的方式。
