Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6α-oxide and certain xenobiotic alkene and arene oxides

Levin, Wayne; Michaud, Dennis P.; Thomas, Paul E.; Jerina, Donald M.

doi:10.1016/0003-9861(83)90439-3

Cited by 79 publications

(14 citation statements)

References 27 publications

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“…As indicated previously, cholesterol oxide hydrolase is a distinct enzyme from oxidosqualene cyclase, as well as from microsomal epoxide hydrolase, the latter being responsible for the metabolism of a wide range of xenobiotic alkene and arene oxides [4,1,5]. Although the cholesterol 5,6 b-oxide is more reactive than the a-oxide upon acid-catalyzed hydration, the a-oxide is a 4.5-fold better substrate than the b-oxide as indicated by values of V max /K m [1].…”

Section: Substrates and Inhibitorsmentioning

confidence: 71%

Epoxide hydrolases: biochemistry and molecular biology

Fretland

Omiecinski

2000

Chemico-Biological Interactions

273

185

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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. 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 A 3 hydrolase, leukotriene A 4 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.

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Section: Substrates and Inhibitorsmentioning

confidence: 71%

Epoxide hydrolases: biochemistry and molecular biology

Fretland

Omiecinski

2000

Chemico-Biological Interactions

273

185

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“…Recently, it was found [14] that in rat liver fractions the microsomal hydration of cholesterol 5,6 a-oxide is catalysed by an epoxide hydrolase which differs markedly from the well-characterized microsomal enzyme. Other studies [15] have shown that cholesterol epoxide is also hydrolysed by rat liver cytosolic fractions; thus, it is tempting to speculate that microsomal cholesterol 5,6 a-oxide hydrolase [14] is actually located in peroxisomes present in the microsomal fractions. In addition, an involve-228 ment of peroxisomes in the cholesterol metabolism has been proposed in [16].…”

Section: Resultsmentioning

confidence: 99%

Epoxide hydrolase activity in isolated peroxisomes of mouse liver

et al. 1983

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“…Microsomal EH catalyzes the hydration of a wide variety of epoxides including xenobiotics (Seidegard and DePierre, 1983). Cholesterol EH is also localized in the microsomes, but-it hydrates compounds related to the 5,6-epoxide of cholesterol (Finley and Hammock, 1988;Levin et aL, 1983). Soluble EH is localized both in the cytosol and in peroxisomes, and it acts on a variety of noncyclic epoxides (Gill et al, 1974;Meijier and DePierre, 1988).…”

Section: Introductionmentioning

confidence: 99%

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

et al. 1994

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SummaryA cDNA (1122 bp) was isolated from a cDNA library prepared from Arabidopais thaliana L. that had been subjected to drought stress for I h. The sequencing of a genomic clone corresponding to the cDNA and Sl mepplng analysis revealed that the cDNA lacked the first 6 bp from its translational start (ATG). The resulting open reading frame encodes a polypaptlde of 321 amino acids, and the calculated molecular weight of this polypeptide is 36 423 De. The deduced amino acid sequence shows a high degree of similarity to C terminal halves of those of soluble epoxide hydrolases (sEHs) of human, mouse and rat, 35.5%, 34.1% and 33.1%, respectively. The cDNA was expressed In Escherichla coil cells, and the expressed protein migrates at 40 kDa when analyzed by SDS-PAGE. The recombinant protein at 40 kDa Is much smaller than the mammalian sEH (58 kDa) but has characteristics of activity and inhibition slmller to the mammalian sEHs when assayed with the substrate trans-stilbene oxide and the inhibitors 4-fluorochalcone oxide (4FCO), (2R,3R)-3-(4-nitrophenyl) glycidol (RRNPG), and (2S,3S)-3-(4-nitrophenyl)glycidol (SSNPG), which indicates that the cDNA did encode a soluble epoxide hydrolese of A. thallana (AtsEH). Drought stress, but not heat or cold stress, slightly Increased the accu-

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Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6α-oxide and certain xenobiotic alkene and arene oxides

Cited by 79 publications

References 27 publications

Epoxide hydrolases: biochemistry and molecular biology

Epoxide hydrolases: biochemistry and molecular biology

Epoxide hydrolase activity in isolated peroxisomes of mouse liver

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

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