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Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid.

ABSTRACT: Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed genome-wide screening of mouse cytochrome P450 (CYP) isoforms to explore enzymes involved in omega-3 oxygenation of EPA. As a result, 5 CYP isoforms (mouse Cyp1a2, 2c50, 4a12a, 4a12b, and 4f18) were selected and identified to confer omega-3 epoxidation of EPA to yield 17,18-epoxyeicosatetraenoic acid (17,18-EpETE). Stereoselective production of 17,18-EpETE by each CYP isoform was confirmed, and molecular modeling indicated that chiral differences stem from different EPA binding conformations in the catalytic domains of respective CYP enzymes.

SUBMITTER: Isobe Y

PROVIDER: S-EPMC5962638 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid.

Isobe Yosuke Y Itagaki Mai M Ito Yuko Y Naoe Satoko S Kojima Kotoe K Ikeguchi Mitsunori M Arita Makoto M

Scientific reports 20180521 1

Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed genome-wide screening of mouse cytochrome P450 (CYP) isoforms to explore enzymes involved in omega-3 oxygenation of EPA. As a result, 5 CYP isoforms (mouse Cyp1a2, 2c50, 4a12a, 4a12b, and 4f18) were selec ...[more]

PMID: 29784972

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