title: Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism.
abstract: Polyunsaturated fatty acids (PUFA) are oxidized by cytochrome P450 epoxygenases to PUFA epoxides which function as potent lipid mediators. The major metabolic pathways of PUFA epoxides are incorporation into phospholipids and hydrolysis to the corresponding PUFA diols by soluble epoxide hydrolase. Inhibitors of soluble epoxide hydrolase stabilize PUFA epoxides and potentiate their functional effects. The epoxyeicosatrienoic acids (EETs) synthesized from arachidonic acid produce vasodilation, stimulate angiogenesis, have anti-inflammatory actions, and protect the heart against ischemia-reperfusion injury. EETs produce these functional effects by activating receptor-mediated signaling pathways and ion channels. The epoxyeicosatetraenoic acids synthesized from eicosapentaenoic acid and epoxydocosapentaenoic acids synthesized from docosahexaenoic acid are potent inhibitors of cardiac arrhythmias. Epoxydocosapentaenoic acids also inhibit angiogenesis, decrease inflammatory and neuropathic pain, and reduce tumor metastasis. These findings indicate that a number of the beneficial functions of PUFA may be due to their conversion to PUFA epoxides. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".
authors.affiliation: Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Electronic address: spectora@mail.nih.gov.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Spector
authors.affiliation: Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hee-Yong
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004194:Disease; D004852:Epoxy Compounds / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes; D015398:Signal Transduction
chemical_list: D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System
keywords: Arachidonic acid (AA); Docosahexaenoic acid (DHA); Eicosapentaenoic acid (EPA); Epoxydocosapentaenoic acid (EpDPE); Epoxyeicosatetraenoic acid (EpETE); Epoxyeicosatrienoic acid (EET)
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