Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily

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Item Type:	Article
Title:	Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily
Creators Name:	Barbosa-Sicard, E., Markovic, M., Honeck, H., Christ, B., Muller, D.N. and Schunck, W.H.
Abstract:	CYP2C enzymes epoxidize arachidonic acid (AA) to metabolites involved in the regulation of vascular and renal function. We tested the hypothesis that eicosapentaenoic acid (EPA), a n-3 polyunsaturated fatty acid, may serve as an alternative substrate. Human CYP2C8 and CYP2C9, as well as rat CYP2C11 and CYP2C23, were co-expressed with NADPH-CYP reductase in a baculovirus/insect cell system. The recombinant enzymes showed high EPA and AA epoxygenase activities and the catalytic efficiencies were almost equal comparing the two substrates. The 17,18-double bond was the preferred site of EPA epoxidation by CYPs 2C8, 2C11, and 2C23. 17(R),18(S)-Epoxyeicosatetraenoic acid was produced with an optical purity of about 70% by CYPs 2C9, 2C11, and 2C23 whereas CYP2C8 showed the opposite enantioselectivity. These results demonstrate that EPA is an efficient substrate of CYP2C enzymes and suggest that n-3 PUFA-rich diets may shift the CYP2C-dependent generation of physiologically active eicosanoids from AA- to EPA-derived metabolites.
Keywords:	CYP2C11, CYP2C23, CYP2C8, CYP2C9, Cytochrome P450, Eicosanoid, Eicosapentaenoic Acid, Epoxidation, N-3 Polyunsaturated Fatty Acid, Animals, Rats
Source:	Biochemical and Biophysical Research Communications
ISSN:	0006-291X
Publisher:	Academic Press
Volume:	329
Number:	4
Page Range:	1275-1281
Date:	22 April 2005
Official Publication:	https://doi.org/10.1016/j.bbrc.2005.02.103
PubMed:	View item in PubMed

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