Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
Isobe Y, Itagaki M, Ito Y, Naoe S, Kojima K, Ikeguchi M, Arita M
Scientific reports · 34 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- Japan Society for the Promotion of Science
- University or hospital
- RIKEN
- Grants
- Japan Society for the Promotion of Science (15H04648); Japan Society for the Promotion of Science (KAKENHI JP15H05897); Japan Society for the Promotion of Science (15H05898); Japan Society for the Promotion of Science (JP15H05897); Japan Society for the Promotion of Science (15H05897)
Based on 2 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-05-15 · Sci Rep · vol. 8 · issue 1 · p. 7954
- Publisher
- Nature Portfolio
- Cited
- 38 citations · more than 83% of similar papers · 1.9× the field average
- References
- 52 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Eicosanoids and Hypertension Pharmacology · Fatty Acid Research and Health · Alcohol Consumption and Health Effects
- Keywords
- Eicosapentaenoic acid, Cytochrome P450, CYP1A2, Gene isoform, Biochemistry, Enzyme, Chemistry, Cytochrome, Biology, Fatty acid, Gene, Polyunsaturated fatty acid
- MeSH
- animals, humans, mice, cytochrome p-450 enzyme system, fatty acids, omega-3, protein conformation, oxidation-reduction, stereoisomerism
7 authors
From JP
- Yosuke Isobe · correspondingRIKEN Center for Integrative Medical Sciences; Yokohama City University
- Mai ItagakiRIKEN Center for Integrative Medical Sciences; Yokohama City University
- Yuko ItoNational Institute of Advanced Industrial Science and Technology; Yokohama City University
- Satoko NaoeRIKEN Center for Integrative Medical Sciences
- Kotoe KojimaRIKEN Center for Integrative Medical Sciences; Yokohama City University
- Mitsunori IkeguchiYokohama City University
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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