Fer Maude, Dréano Yvonne, Lucas Danièle, Corcos Laurent, Salaün Jean-Pierre, Berthou François, Amet Yolande
Laboratoire de Biochimie EA948, Faculté de Médecine, 22 Av Camille Desmoulins, CS 93837, 29238 BREST Cedex 3, France.
Arch Biochem Biophys. 2008 Mar 15;471(2):116-25. doi: 10.1016/j.abb.2008.01.002. Epub 2008 Jan 11.
Epoxidation and hydroxylation of arachidonic acid (AA) are both catalyzed by cytochromes P450s (CYPs). The oxidized metabolites are known to be involved in the regulation of vascular tone and renal function. By using a panel of 15 human recombinant CYPs, this study demonstrates that other polyunsaturated long-chain fatty acids (PUFA-LC), especially the omega3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are also epoxidised. The regioselectivity of epoxidation of four PUFA-LC by CYPs was investigated. Among the several CYPs tested, CYP2C9/2C19 and 1A2 were the most efficient in EPA and DHA epoxidations. It ensued that 10muM of these two omega3 fatty acids decreased by more than 80% and 60%, respectively, the formation by CYP2C9 of AA-epoxidised derivatives. These findings suggest that some physiological effects of omega3 fatty acids may be due to a shift in the generation of active epoxidised metabolites of AA through CYP-mediated catalysis.
花生四烯酸（AA）的环氧化和羟基化均由细胞色素P450（CYPs）催化。已知氧化代谢产物参与血管张力和肾功能的调节。通过使用一组15种人类重组CYPs，本研究表明其他多不饱和长链脂肪酸（PUFA-LC），尤其是ω-3脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），也会被环氧化。研究了CYPs对四种PUFA-LC环氧化的区域选择性。在测试的几种CYPs中，CYP2C9/2C19和1A2在EPA和DHA环氧化中效率最高。结果表明，10μM的这两种ω-3脂肪酸分别使CYP2C9形成的AA环氧化衍生物减少了80%以上和60%以上。这些发现表明，ω-3脂肪酸的一些生理效应可能是由于通过CYP介导的催化作用，AA活性环氧化代谢产物的生成发生了转变。
