Epoxide hydrolases

Biochemistry and molecular biology

Adrian J. Fretland, Curtis John Omiecinski

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

Epoxides are organic three-membered oxygen compounds that arise from oxidative metabolism of endogenous, as well as xenobiotic compounds via chemical and enzymatic oxidation processes, including the cytochrome P450 monooxygenase system. The resultant epoxides are typically unstable in aqueous environments and chemically reactive. In the case of xenobiotics and certain endogenous substances, epoxide intermediates have been implicated as ultimate mutagenic and carcinogenic initiators Adams et al. (Chem. Biol. Interact. 95 (1995) 57-77) Guengrich (Properties and Metabolic roles 4 (1982) 5-30) Sayer et al. (J. Biol. Chem. 260 (1985) 1630-1640). Therefore, it is of vital importance for the biological organism to regulate levels of these reactive species. The epoxide hydrolases (E.C. 3.3.2.3) belong to a sub-category of a broad group of hydrolytic enzymes that include esterases, proteases, dehalogenases, and lipases Beetham et al. (DNA Cell Biol. 14 (1995) 61-71). In particular, the epoxide hydrolases are a class of proteins that catalyze the hydration of chemically reactive epoxides to their corresponding dihydrodiol products. Simple epoxides are hydrated to their corresponding vicinal dihydrodiols, and arene oxides to trans-dihydrodiols. In general, this hydration leads to more stable and less reactive intermediates, however exceptions do exist. In mammalian species, there are at least five epoxide hydrolase forms, microsomal cholesterol 5,6-oxide hydrolase, hepoxilin A3 hydrolase, leukotriene A4 hydrolase, soluble, and microsomal epoxide hydrolase. Each of these enzymes is distinct chemically and immunologically. Table 1 illustrates some general properties for each of these classes of hydrolases. Fig. 1 provides an overview of selected model substrates for each class of epoxide hydrolase.

Original languageEnglish (US)
Pages (from-to)41-59
Number of pages19
JournalChemico-Biological Interactions
Volume129
Issue number1-2
DOIs
StatePublished - Dec 1 2000

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Epoxide Hydrolases
Biochemistry
Molecular biology
Epoxy Compounds
Molecular Biology
Hydrolases
Xenobiotics
Hydration
Oxides
Oxygen Compounds
Esterases
Enzymes
Mixed Function Oxygenases
Lipase
Metabolism
Cytochrome P-450 Enzyme System
Peptide Hydrolases
Cholesterol
Oxidation
DNA

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Fretland, Adrian J. ; Omiecinski, Curtis John. / Epoxide hydrolases : Biochemistry and molecular biology. In: Chemico-Biological Interactions. 2000 ; Vol. 129, No. 1-2. pp. 41-59.
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Epoxide hydrolases : Biochemistry and molecular biology. / Fretland, Adrian J.; Omiecinski, Curtis John.

In: Chemico-Biological Interactions, Vol. 129, No. 1-2, 01.12.2000, p. 41-59.

Research output: Contribution to journalArticle

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