EH3 (ABHD9)

The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides

Martina Decker, Magdalena Adamska, Annette Cronin, Francesca Di Giallonardo, Julia Burgener, Anne Marowsky, J R Falck, Christophe Morisseau, Bruce D. Hammock, Artiom Gruzdev, Darryl C. Zeldin, Michael Arand

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2038-2045
Number of pages8
JournalJournal of Lipid Research
Volume53
Issue number10
DOIs
StatePublished - Oct 2012

Fingerprint

Epoxide Hydrolases
Epoxy Compounds
Fatty Acids
Forensic Anthropology
Detoxification
Upper Gastrointestinal Tract
Xenobiotics
Enzymes
Medical problems
Type 2 Diabetes Mellitus
Urea
Skin
Clinical Trials
Tissue
Hypertension
Derivatives
Polymerase Chain Reaction
Lung
Molecules
Acids

Keywords

  • Blood pressure
  • Diabetes type II
  • Epoxyeicosatrienoic acid
  • Pain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Decker, M., Adamska, M., Cronin, A., Di Giallonardo, F., Burgener, J., Marowsky, A., ... Arand, M. (2012). EH3 (ABHD9): The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides. Journal of Lipid Research, 53(10), 2038-2045. https://doi.org/10.1194/jlr.M024448

EH3 (ABHD9) : The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides. / Decker, Martina; Adamska, Magdalena; Cronin, Annette; Di Giallonardo, Francesca; Burgener, Julia; Marowsky, Anne; Falck, J R; Morisseau, Christophe; Hammock, Bruce D.; Gruzdev, Artiom; Zeldin, Darryl C.; Arand, Michael.

In: Journal of Lipid Research, Vol. 53, No. 10, 10.2012, p. 2038-2045.

Research output: Contribution to journalArticle

Decker, M, Adamska, M, Cronin, A, Di Giallonardo, F, Burgener, J, Marowsky, A, Falck, JR, Morisseau, C, Hammock, BD, Gruzdev, A, Zeldin, DC & Arand, M 2012, 'EH3 (ABHD9): The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides', Journal of Lipid Research, vol. 53, no. 10, pp. 2038-2045. https://doi.org/10.1194/jlr.M024448
Decker, Martina ; Adamska, Magdalena ; Cronin, Annette ; Di Giallonardo, Francesca ; Burgener, Julia ; Marowsky, Anne ; Falck, J R ; Morisseau, Christophe ; Hammock, Bruce D. ; Gruzdev, Artiom ; Zeldin, Darryl C. ; Arand, Michael. / EH3 (ABHD9) : The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides. In: Journal of Lipid Research. 2012 ; Vol. 53, No. 10. pp. 2038-2045.
@article{7d7237dc8d3a41b687ce0fa823a927da,
title = "EH3 (ABHD9): The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides",
abstract = "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.",
keywords = "Blood pressure, Diabetes type II, Epoxyeicosatrienoic acid, Pain",
author = "Martina Decker and Magdalena Adamska and Annette Cronin and {Di Giallonardo}, Francesca and Julia Burgener and Anne Marowsky and Falck, {J R} and Christophe Morisseau and Hammock, {Bruce D.} and Artiom Gruzdev and Zeldin, {Darryl C.} and Michael Arand",
year = "2012",
month = "10",
doi = "10.1194/jlr.M024448",
language = "English (US)",
volume = "53",
pages = "2038--2045",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

TY - JOUR

T1 - EH3 (ABHD9)

T2 - The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides

AU - Decker, Martina

AU - Adamska, Magdalena

AU - Cronin, Annette

AU - Di Giallonardo, Francesca

AU - Burgener, Julia

AU - Marowsky, Anne

AU - Falck, J R

AU - Morisseau, Christophe

AU - Hammock, Bruce D.

AU - Gruzdev, Artiom

AU - Zeldin, Darryl C.

AU - Arand, Michael

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - Blood pressure

KW - Diabetes type II

KW - Epoxyeicosatrienoic acid

KW - Pain

UR - http://www.scopus.com/inward/record.url?scp=84866150711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866150711&partnerID=8YFLogxK

U2 - 10.1194/jlr.M024448

DO - 10.1194/jlr.M024448

M3 - Article

VL - 53

SP - 2038

EP - 2045

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 10

ER -