Document Detail


EH3 (ABHD9): the first member of a new epoxide hydrolase family with high activity for fatty acid epoxides.
MedLine Citation:
PMID:  22798687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epoxide hydrolases are a small superfamily of enzymes important for the detoxification of chemically reactive xenobiotic epoxides and for the processing of endogenous epoxides that act as signaling molecules. Here, we report the identification of two human epoxide hydrolases: EH3 and EH4. They share 45% sequence identity, thus representing a new family of mammalian epoxide hydrolases. Quantitative RT-PCR from mouse tissue indicates strongest EH3 expression in lung, skin, and upper gastrointestinal tract. The recombinant enzyme shows a high turnover number with 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET), as well as 9,10-epoxyoctadec-11-enoic acid (leukotoxin). It is inhibited by a subclass of N,N'-disubstituted urea derivatives, including 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, 1-cyclohexyl-3-dodecylurea, and 1-(1-acetylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea, compounds so far believed to be selective inhibitors of mammalian soluble epoxide hydrolase (sEH). Its sensitivity to this subset of sEH inhibitors may have implications on the pharmacologic profile of these compounds. This is particularly relevant because sEH is a potential drug target, and clinical trials are under way exploring the value of sEH inhibitors in the treatment of hypertension and diabetes type II.
Authors:
Martina Decker; Magdalena Adamska; Annette Cronin; Francesca Di Giallonardo; Julia Burgener; Anne Marowsky; John R Falck; Christophe Morisseau; Bruce D Hammock; Artiom Gruzdev; Darryl C Zeldin; Michael Arand
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-12
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-07     Completed Date:  2013-01-29     Revised Date:  2013-10-10    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2038-45     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
8,11,14-Eicosatrienoic Acid / analogs & derivatives,  metabolism
Animals
Epoxide Hydrolases / antagonists & inhibitors,  chemistry,  metabolism*
Epoxy Compounds / metabolism
Humans
Metabolic Detoxication, Drug
Mice
Mice, Inbred C57BL
Phylogeny
Stearic Acids / metabolism
Xenobiotics / metabolism
Grant Support
ID/Acronym/Agency:
GM-31278/GM/NIGMS NIH HHS; P01 DK038226/DK/NIDDK NIH HHS; R01 ES002710/ES/NIEHS NIH HHS; R01-ES-002710/ES/NIEHS NIH HHS; R01-HL-059699/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Epoxy Compounds; 0/Stearic Acids; 0/Xenobiotics; 2443-39-2/9,10-epoxystearic acid; 7324-41-6/8,11,14-Eicosatrienoic Acid; 81276-03-1/14,15-epoxy-5,8,11-eicosatrienoic acid; EC 3.3.2.-/EH3 protein, human; EC 3.3.2.-/EH4 protein, human; EC 3.3.2.-/Epoxide Hydrolases
Comments/Corrections

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