Role of Epoxide Hydrolases in Lipid Metabolism

Overview

Journal Biochimie

Specialty Biochemistry

Date 2012 Jun 23

PMID 22722082

Citations 34

Authors

Christophe Morisseau

Affiliations

Soon will be listed here.

Abstract

Epoxide hydrolases (EH), enzymes present in all living organisms, transform epoxide-containing lipids to 1,2-diols by the addition of a molecule of water. Many of these oxygenated lipid substrates have potent biological activities: host defense, control of development, regulation of blood pressure, inflammation, and pain. In general, the bioactivity of these natural epoxides is significantly reduced upon metabolism to diols. Thus, through the regulation of the titer of lipid epoxides, EHs have important and diverse biological roles with profound effects on the physiological state of the host organism. This review will discuss the biological activity of key lipid epoxides in mammals. In addition, the use of EH specific inhibitors will be highlighted as possible therapeutic disease interventions.

Citing Articles

Peroxisomal core structures segregate diverse metabolic pathways.

Backer N, Ast J, Martorana D, Renicke C, Berger J, Mais C Nat Commun. 2025; 16(1):1802.

PMID: 39979331 PMC: 11842775. DOI: 10.1038/s41467-025-57053-9.

Bromination and conversion of tetrahydro-1H-indene to bisoxirane with a new approach: synthesis, structural characterization by spectroscopic and theoretical methods, and biological analysis supported by DFT and docking.

Yilmaz R, Erkan S, Okten S, Tutar A, Sahin E Turk J Chem. 2024; 47(6):1459-1478.

PMID: 38544714 PMC: 10965191. DOI: 10.55730/1300-0527.3628.

Molecular responses of agroinfiltrated Nicotiana benthamiana leaves expressing suppressor of silencing P19 and influenza virus-like particles.

Hamel L, Tardif R, Poirier-Gravel F, Rasoolizadeh A, Brosseau C, Giroux G Plant Biotechnol J. 2023; 22(5):1078-1100.

PMID: 38041470 PMC: 11022802. DOI: 10.1111/pbi.14247.

The Cholesterol-5,6-Epoxide Hydrolase: A Metabolic Checkpoint in Several Diseases.

de Medina P, Ayadi S, Diallo K, Bunay J, Pucheu L, Soules R Adv Exp Med Biol. 2023; 1440:149-161.

PMID: 38036879 DOI: 10.1007/978-3-031-43883-7_8.

Engineering lanthipeptides by introducing a large variety of RiPP modifications to obtain new-to-nature bioactive peptides.

Fu Y, Xu Y, Ruijne F, Kuipers O FEMS Microbiol Rev. 2023; 47(3).

PMID: 37096385 PMC: 10373908. DOI: 10.1093/femsre/fuad017.

References

Morisseau C, Goodrow M, Dowdy D, Zheng J, Greene J, Sanborn J . Potent urea and carbamate inhibitors of soluble epoxide hydrolases. Proc Natl Acad Sci U S A. 1999; 96(16):8849-54. PMC: 17696. DOI: 10.1073/pnas.96.16.8849. View

Newman J, Morisseau C, Harris T, Hammock B . The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci U S A. 2003; 100(4):1558-63. PMC: 149871. DOI: 10.1073/pnas.0437724100. View

Rudberg P, Tholander F, Thunnissen M, Haeggstrom J . Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms. J Biol Chem. 2001; 277(2):1398-404. DOI: 10.1074/jbc.M106577200. View

Newman J, Morisseau C, Hammock B . Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog Lipid Res. 2005; 44(1):1-51. DOI: 10.1016/j.plipres.2004.10.001. View

Cronin A, Decker M, Arand M . Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase. J Lipid Res. 2011; 52(4):712-9. PMC: 3284163. DOI: 10.1194/jlr.M009639. View

Marowsky A, Burgener J, Falck J, Fritschy J, Arand M . Distribution of soluble and microsomal epoxide hydrolase in the mouse brain and its contribution to cerebral epoxyeicosatrienoic acid metabolism. Neuroscience. 2009; 163(2):646-61. DOI: 10.1016/j.neuroscience.2009.06.033. View

van Loo B, Kingma J, Arand M, Wubbolts M, Janssen D . Diversity and biocatalytic potential of epoxide hydrolases identified by genome analysis. Appl Environ Microbiol. 2006; 72(4):2905-17. PMC: 1448995. DOI: 10.1128/AEM.72.4.2905-2917.2006. View

Kaneko-Ishino T, Kuroiwa Y, Miyoshi N, Kohda T, Suzuki R, Yokoyama M . Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization. Nat Genet. 1995; 11(1):52-9. DOI: 10.1038/ng0995-52. View

Arand M, Hallberg B, Zou J, Bergfors T, Oesch F, van der Werf M . Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site. EMBO J. 2003; 22(11):2583-92. PMC: 156771. DOI: 10.1093/emboj/cdg275. View

10.

Fulton D, Falck J, McGiff J, Carroll M, Quilley J . A method for the determination of 5,6-EET using the lactone as an intermediate in the formation of the diol. J Lipid Res. 1998; 39(8):1713-21. View

11.

Wijekoon C, Goodwin P, Valliani M, Hsiang T . The role of a putative peroxisomal-targeted epoxide hydrolase of Nicotiana benthamiana in interactions with Colletotrichum destructivum, C. orbiculare or Pseudomonas syringae pv. tabaci. Plant Sci. 2011; 181(2):177-87. DOI: 10.1016/j.plantsci.2011.05.004. View

12.

JACOBS M, van den Wijngaard A, Pentenga M, Janssen D . Characterization of the epoxide hydrolase from an epichlorohydrin-degrading Pseudomonas sp. Eur J Biochem. 1991; 202(3):1217-22. DOI: 10.1111/j.1432-1033.1991.tb16493.x. View

13.

Wagner K, Inceoglu B, Hammock B . Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception. Prostaglandins Other Lipid Mediat. 2011; 96(1-4):76-83. PMC: 3215909. DOI: 10.1016/j.prostaglandins.2011.08.001. View

14.

Morisseau C, Schebb N, Dong H, Ulu A, Aronov P, Hammock B . Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids. Biochem Biophys Res Commun. 2012; 419(4):796-800. PMC: 3313618. DOI: 10.1016/j.bbrc.2012.02.108. View

15.

Decker M, Arand M, Cronin A . Mammalian epoxide hydrolases in xenobiotic metabolism and signalling. Arch Toxicol. 2009; 83(4):297-318. DOI: 10.1007/s00204-009-0416-0. View

16.

Bahl C, Morisseau C, Bomberger J, Stanton B, Hammock B, OToole G . Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site features of an epoxide hydrolase virulence factor. J Bacteriol. 2010; 192(7):1785-95. PMC: 2838060. DOI: 10.1128/JB.01348-09. View

17.

Kachroo A, Kachroo P . Fatty Acid-derived signals in plant defense. Annu Rev Phytopathol. 2009; 47:153-76. DOI: 10.1146/annurev-phyto-080508-081820. View

18.

Li Y, Beisson F . The biosynthesis of cutin and suberin as an alternative source of enzymes for the production of bio-based chemicals and materials. Biochimie. 2009; 91(6):685-91. DOI: 10.1016/j.biochi.2009.03.016. View

19.

Khlebodarova T, Gruntenko N, Grenback L, Sukhanova M, Mazurov M, Rauschenbach I . A comparative analysis of juvenile hormone metabolyzing enzymes in two species of Drosophila during development. Insect Biochem Mol Biol. 1996; 26(8-9):829-35. DOI: 10.1016/s0965-1748(96)00043-4. View

20.

Morisseau C, Inceoglu B, Schmelzer K, Tsai H, Jinks S, Hegedus C . Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J Lipid Res. 2010; 51(12):3481-90. PMC: 2975720. DOI: 10.1194/jlr.M006007. View