Arachidonate Epoxygenase / Epoxide Hydrolase (Homo sapiens)

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Description

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.

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Fatty Acid Epoxygenase
 
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Bibliography

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History

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CompareRevisionActionTimeUserComment
71506view19:21, 17 October 2013MaintBotremoved data source from nodes without identifier
67058view10:00, 26 June 2013Christine ChichesterOntology Term : 'arachidonic acid metabolic pathway' added !
63166view20:24, 8 May 2013MaintBotUpdating GPML version
59189view19:02, 22 February 2013MaintBotUpdated Ensembl data source
44962view12:48, 6 October 2011MartijnVanIerselOntology Term : 'metabolic pathway of secondary metabolites' added !
41165view23:41, 1 March 2011MaintBotRemoved redundant pathway information and comments
38950view00:05, 25 September 2010KhanspersChanged layout
38949view00:02, 25 September 2010Khanspers
33404view14:48, 30 November 2009MaintBotRemoved group label
30254view04:39, 25 July 2009AlexanderPicoModified categories
29908view12:13, 9 June 2009Thomasupdated ensembl references
29111view05:25, 3 April 2009JwnewmanModified description
29110view05:12, 3 April 2009JwnewmanPeriodical save, work in progress
28979view15:33, 19 March 2009EveloCorrecte COX annotation to something that *might* be right
28976view13:22, 19 March 2009EveloSpecify description
28975view13:18, 19 March 2009EveloPeriodical save, work in progress
28974view13:08, 19 March 2009EveloPeriodical save, work in progress
28973view12:45, 19 March 2009MartijnVanIerselNew pathway

External references

View all...
NameTypeDatabase referenceComment
Glutathionyl-HETrEsMetabolite
Arachidonic acidMetaboliteHMDB01043 (HMDB)
8,9-DiHETrEMetaboliteHMDB02311 (HMDB)
14(15)-EpETrEMetaboliteHMDB04264 (HMDB)
5,6-DiH-PGF1aMetabolite
CYP2C9GeneProduct1559 (Entrez Gene)
5(6)-Epoxy-PGE1Metabolite
11(12)-EpETrEMetaboliteHMDB10409 (HMDB)
Phosphotidyl-EpETrEsMetabolite
8(9)-EpETrEMetaboliteHMDB02232 (HMDB)
CYP2J2GeneProductENSG00000134716 (Ensembl)
5(6)-EpETrEMetaboliteHMDB02190 (HMDB)
CYP2C8GeneProduct1558 (Entrez Gene)
11,12-DiHETrEMetaboliteHMDB02314 (HMDB)
COXGeneProduct9377 (Entrez Gene)
EPHX2GeneProduct2053 (Entrez Gene)
GST3GeneProduct2950 (Entrez Gene)
14,15-DiHETrEMetaboliteHMDB02265 (HMDB)
CatalystGeneProduct
5,6-DiHETrEMetaboliteHMDB02343 (HMDB)
COXGeneProduct1351 (Entrez Gene)
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