Metabolism of eicosapentaenoic and docosahexaenoic acids by recombinant human cytochromes P450.

Abstract:

: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.

journal_name

Arch Biochem Biophys

authors

Fer M,Dréano Y,Lucas D,Corcos L,Salaün JP,Berthou F,Amet Y

doi

10.1016/j.abb.2008.01.002

subject

Has Abstract

pub_date

2008-03-15 00:00:00

pages

116-25

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(08)00004-0

journal_volume

471

pub_type

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