Arachidonate epoxygenase / epoxide hydrolase (WP678)

Homo sapiens

The cytochrome P450-dependent formation of polyunsaturated fatty acid epoxides is an important biochemical pathway creating mediators of inflammation and blood pressure regulation. Once formed these compounds can be incorperated into phospholipid membrance, and released by the action of phospholipase A2. The epoxides of arachidonic acid, i.e. the epoxyeicosatrieneoic acid or EETs, are putative endothelial derived hyperpolarization factors which increase the open state probability of Ca++ sensitive K+ channels, leading to vasodilation in arteriolar beds. The 11(12)-EET in particular appears to have potent functions in vasodilation, and are inhibitors of NFKb dependent inflammatory signalling, and PAI-1 activity. The 5(6)-EET appears unique, in that its metabolic transformation through cyclooxygenase activities produces potent vasoconstrictors. With the exception of the 5(6)-EET, these epoxy fatty acids are good substrates for the soluble epoxide hydrolase. Hydrolytic tranformation to vicinal diols eliminates vasoactive actions, however these vicinal diols have been reported to have other biological activites, including PPAR-alpha activation. Recent development of inhibitors of the soluble epoxide hydrolase are proving to have potent anti-inflammatory, anti-hypertensive, and anti-nociceptive properties. Reports of enzyme catalyzed glutathione-conjugates of the epoxy fatty acids have been reported, but the activity and relavance of these potential metabolic products are unknown to date.


Martijn Van Iersel , Chris Evelo , John W. Newman , Thomas Kelder , Alex Pico , Kristina Hanspers , Christine Chichester , Denise Slenter , Eric Weitz , and Egon Willighagen


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Homo sapiens



Pathway Ontology

metabolic pathway of secondary metabolites arachidonic acid metabolic pathway


Label Type Compact Identifier Comment
11,12-DiHETrE Metabolite hmdb:HMDB0002314
14(15)-EpETrE Metabolite hmdb:HMDB0004264
5(6)-Epoxy-PGE1 Metabolite pubchem.compound:53481368
5,6-DiHETrE Metabolite hmdb:HMDB0002343
8(9)-EpETrE Metabolite hmdb:HMDB0002232
5(6)-EpETrE Metabolite hmdb:HMDB0002190
11(12)-EpETrE Metabolite hmdb:HMDB0010409
8,9-DiHETrE Metabolite hmdb:HMDB0002311
14,15-DiHETrE Metabolite hmdb:HMDB0002265
Arachidonic acid Metabolite hmdb:HMDB0001043
CYP2C9 GeneProduct ncbigene:1559
EPHX2 GeneProduct ncbigene:2053
COX GeneProduct ncbigene:9377
EPHX2 GeneProduct ncbigene:2053
EPHX2 GeneProduct ncbigene:2053
CYP2C8 GeneProduct ncbigene:1558
GST3 GeneProduct ncbigene:2950
COX GeneProduct ncbigene:1351
CYP2J2 GeneProduct ensembl:ENSG00000134716
EPHX2 GeneProduct ncbigene:2053 5(6)-EpETrE is a poor sEH substrate
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