Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function.
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 Ca(2+) 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 beta-oxidation, and the accumulation of partial beta-oxidation products increases when sEH is inhibited. Some functional effects of EETs occur through activation of either the guanine nucleotide binding protein Galphas 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.
Spector
Arthur A
AA
Department of Biochemistry, 4-403 Bowen Science Building, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. arthur-spector@uiowa.edu
Fang
Xiang
X
Snyder
Gary D
GD
Weintraub
Neal L
NL
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007473:Ion Channels; D007668:Kidney / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism
D001685:Biological Factors; D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D007473:Ion Channels; D010743:Phospholipids; C067410:endothelium-dependent hyperpolarization factor; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid