Epoxyeicosatrienoic acids (EETs): Metabolism and biochemical function

Arthur A. Spector, Xiang Fang, Gary D. Snyder, Neal L. Weintraub

Research output: Contribution to journalReview articlepeer-review

426 Scopus citations

Abstract

Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. They modulate ion transport and gene expression, producing vasorelaxation as well as anti-inflammatory and pro-fibrinolytic effects. EETs are incorporated into the sn-2 position of phospholipids and are rapidly mobilized when a cell is treated with a Ca2+ ionophore, suggesting that they may play a role in phospholipid-mediated signal transduction processes. Soluble epoxide hydrolase (sEH) converts EETs to dihydroxyeicosatrienoic acids (DHETs), and inhibition of sEH is a potential approach for enhancing the biological activity of EETs. EETs also undergo chain-elongation and β-oxidation, and the accumulation of partial β-oxidation products increases when sEH is inhibited. Some functional effects of EETs occur through activation of either the guanine nucleotide binding protein Gαs or the Src signal transduction pathways, suggesting that EETs act by binding to membrane receptors. However, other evidence indicates that the modulation of gene expression occurs through an intracellular action of EETs. Because of the diversity of biochemical and functional responses produced by EETs, it is doubtful that a single mechanism or signal transduction pathway can account for all of their actions.

Original languageEnglish (US)
Pages (from-to)55-90
Number of pages36
JournalProgress in Lipid Research
Volume43
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Keywords

  • Chain-elongation
  • Cytochrome P450
  • DHET
  • EDHF
  • EET
  • Epoxide hydrolase
  • Inflammation
  • Ion channels
  • Phospholipid
  • Receptor
  • β-Oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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