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

Yosuke Isobe, Mai Itagaki, Yuko Ito, Satoko Naoe, Kotoe Kojima, Mitsunori Ikeguchi, Makoto Arita

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number7954
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Eicosapentaenoic Acid
Cytochrome P-450 Enzyme System
Protein Isoforms
Oxygenases
Acids
Metabolic Networks and Pathways
Catalytic Domain
Anti-Inflammatory Agents
Genome
Lipids
Enzymes

ASJC Scopus subject areas

  • General

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Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid. / Isobe, Yosuke; Itagaki, Mai; Ito, Yuko; Naoe, Satoko; Kojima, Kotoe; Ikeguchi, Mitsunori; Arita, Makoto.

In: Scientific Reports, Vol. 8, No. 1, 7954, 01.12.2018.

Research output: Contribution to journalArticle

Isobe, Yosuke ; Itagaki, Mai ; Ito, Yuko ; Naoe, Satoko ; Kojima, Kotoe ; Ikeguchi, Mitsunori ; Arita, Makoto. / Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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