Arachidonate epoxygenase / epoxide hydrolase (WP1000)

Bos taurus

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.


Egon Willighagen , Martina Summer-Kutmon , and Eric Weitz


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Bos taurus



Pathway Ontology

metabolic pathway of secondary metabolites arachidonic acid metabolic pathway


Label Type Compact URI Comment
11,12-DiHETrE Metabolite hmdb:HMDB0002314
14(15)-EpETrE Metabolite hmdb:HMDB0004264
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 ensembl:ENSBTAG00000020375 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1559
EPHX2 GeneProduct ensembl:ENSBTAG00000015241 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2053
COX5A GeneProduct ensembl:ENSBTAG00000017267 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9377
CYP2C8 GeneProduct ensembl:ENSBTAG00000020375 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1558
GSTP1 GeneProduct ensembl:ENSBTAG00000003548 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2950
COX8A GeneProduct ensembl:ENSBTAG00000004920 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1351
CYP2J2 GeneProduct ensembl:ENSBTAG00000013693 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000134716
EPHX2 GeneProduct ensembl:ENSBTAG00000015241 5(6)-EpETrE is a poor sEH substrate
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2053


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