INSERM, U613, ECLA unit, Brest, F-29200, France.
J Lipid Res. 2010 May;51(5):1125-33. doi: 10.1194/jlr.M003061. Epub 2009 Nov 25.
Cytochromes P450 (CYPs) metabolize polyunsaturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., omega6 in AA or omega3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefin of AA (omega6), EPA (omega3), or DHA (omega3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs.
细胞色素 P450(CYPs)代谢多不饱和长链脂肪酸(PUFA-LC)生成几类含氧代谢物。最近我们利用人重组 CYP 发现 CYP1A1、-2C19、-2D6、-2E1 和 -3A4 主要为羟化酶,而 CYP1A2、-2C8、-2C9 和 -2J2 分别为花生四烯酸(AA)、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)的主要环氧化酶。值得注意的是,这些多不饱和脂肪酸的最后一个双键,即 AA 的ω6 或 EPA 和 DHA 中的ω3,优先被环氧化。在这项研究中,我们通过与从立体选择性细菌 CYP102A1 F87V 获得的 PUFA-LC 环氧化物立体异构体进行比较,对该环氧化反应的立体选择性进行了表征。AA(ω6)、EPA(ω3)或 DHA(ω3)的最后一个烯烃的环氧化立体选择性在 CYP 同工酶之间存在差异,但 EPA 和 DHA 的立体选择性相似。这些数据为肝 CYP 生成的多不饱和脂肪酸环氧化物对映异构体提供了更多的见解。