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. 2020 Aug 26;11:1233. doi: 10.3389/fphar.2020.01233

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Copyright © 2020 Smith, Roque, Ching, Fulton, Rao and Reader

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The cytochrome P450 epoxygenase pathway creates a series of regioisomeric epoxyeicosatrienoic acids (EETs) or hydroperoxyeicosatetraenoic (HETEs). Arachidonic acid (AA) is metabolized by the CYP ω-hydroxylases to 7-, 10-, 12-, 13-, 15-, 16-, 17-, 18-, 19-, and 20-HETEs. HETEs can bind to PPAR intracellularly or bind their receptor on the plasma membrane surface. EETs are metabolized by soluble epoxide hydrolase (sEH) to form the corresponding fatty acid diols. 5,6-EET and 8,9-EET are also substrates for COX-1 and COX-2 forming ct-8,9-E-11-HET and ct-8,9-E-15-HET. EETs can also signal through their cognate receptors.