RGD Reference Report - Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase. - Rat Genome Database

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Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase.

Authors: Cronin, Annette  Decker, Martina  Arand, Michael 
Citation: Cronin A, etal., J Lipid Res. 2011 Apr;52(4):712-9. doi: 10.1194/jlr.M009639. Epub 2011 Jan 7.
RGD ID: 21201254
Pubmed: PMID:21217101   (View Abstract at PubMed)
PMCID: PMC3284163   (View Article at PubMed Central)
DOI: DOI:10.1194/jlr.M009639   (Journal Full-text)

Hepoxilins are lipid signaling molecules derived from arachidonic acid through the 12-lipoxygenase pathway. These trans-epoxy hydroxy eicosanoids play a role in a variety of physiological processes, including inflammation, neurotransmission, and formation of skin barrier function. Mammalian hepoxilin hydrolase, partly purified from rat liver, has earlier been reported to degrade hepoxilins to trioxilins. Here, we report that hepoxilin hydrolysis in liver is mainly catalyzed by soluble epoxide hydrolase (sEH): i) purified mammalian sEH hydrolyses hepoxilin A₃ and B₃ with a V(max) of 0.4-2.5 μmol/mg/min; ii) the highly selective sEH inhibitors N-adamantyl-N'-cyclohexyl urea and 12-(3-adamantan-1-yl-ureido) dodecanoic acid greatly reduced hepoxilin hydrolysis in mouse liver preparations; iii) hepoxilin hydrolase activity was abolished in liver preparations from sEH(-/-) mice; and iv) liver homogenates of sEH(-/-) mice show elevated basal levels of hepoxilins but lowered levels of trioxilins compared with wild-type animals. We conclude that sEH is identical to previously reported hepoxilin hydrolase. This is of particular physiological relevance because sEH is emerging as a novel drug target due to its major role in the hydrolysis of important lipid signaling molecules such as epoxyeicosatrienoic acids. sEH inhibitors might have undesired side effects on hepoxilin signaling.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ephx2Ratepoxide metabolic process involved_inIDA PMID:21217101UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ephx2Ratepoxide hydrolase activity enablesIDA PMID:21217101UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Ephx2  (epoxide hydrolase 2)


Additional Information