Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily
| Autor: | Wolf-Hagen Schunck, Horst Honeck, Marija Markovic, Eduardo Barbosa-Sicard, Baghat Christ, Dominik N. Müller |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Epoxygenase
Stereochemistry Biophysics Spodoptera Biology Cytochrome P-450 CYP2J2 Biochemistry Catalysis Cell Line Substrate Specificity Cytochrome P-450 CYP2C8 chemistry.chemical_compound Cytochrome P-450 Enzyme System Animals Humans Protein Isoforms Cytochrome P450 Family 2 CYP2C8 Molecular Biology CYP2C9 Chromatography High Pressure Liquid Cytochrome P-450 CYP2C9 chemistry.chemical_classification Cytochrome P450 Stereoisomerism Cell Biology Eicosapentaenoic acid Rats Kinetics Enzyme Eicosapentaenoic Acid Steroid 16-alpha-Hydroxylase Eicosanoid chemistry biology.protein lipids (amino acids peptides and proteins) Arachidonic acid Aryl Hydrocarbon Hydroxylases |
| Zdroj: | Biochemical and Biophysical Research Communications. 329:1275-1281 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.02.103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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