Identification and Functional Characterization of Human Soluble Epoxide Hydrolase Genetic Polymorphisms

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Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms.

Human soluble epoxide hydrolase (sEH), an enzyme directing the functional disposition of a variety of endogenous and xenobiotic-derived chemical epoxides, was characterized at the genomic level for interindividual variation capable of impacting function. RNA was isolated from 25 human liver samples and used to generate full-length copies of soluble epoxide hydrolase cDNA. The resulting cDNAs we...

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Polymorphisms in human soluble epoxide hydrolase.

Human soluble epoxide hydrolase (hsEH) metabolizes a variety of epoxides to the corresponding vicinal diols. Arachidonic and linoleic acid epoxides are thought to be endogenous substrates for hsEH. Enzyme activity in humans shows high interindividual variation (e.g., 500-fold in liver) suggesting the existence of regulatory and/or structural gene polymorphisms. We resequenced each of the 19 exo...

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Human microsomal epoxide hydrolase: 5'-flanking region genetic polymorphisms.

Microsomal epoxide hydrolase (mEH) catalyses the hydrolysis of xenobiotic epoxides, including various epoxide derivatives of the procarcinogenic polyaromatic hydrocarbons. Levels of mEH enzymatic activity among different cell types and between individuals within the population vary considerably. Genetic polymorphisms within the structural region of the human mEH gene exist and appear to contrib...

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Functional analysis of human microsomal epoxide hydrolase genetic variants.

Human microsomal epoxide hydrolase (EPHX1) is active in the metabolism of many potentially carcinogenic or otherwise genotoxic epoxides, such as those derived from the oxidation of polyaromatic hydrocarbons. EPHX1 is polymorphic and encodes allelic variation at least two amino acid positions, Y113H and H139R. In a number of recent molecular epidemiological investigations, EPHX1 polymorphism has...

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Microsomal epoxide hydrolase polymorphisms.

Microsomal epoxide hydrolase plays a dual role in the activation and detoxification of carcinogenic compounds. Two polymorphic sites have been described in exons 3 and 4 of the microsomal epoxide hydrolase gene that change tyrosine residue 113 to histidine (Tyr113His) and histidine 139 to arginine (His139Arg), respectively. The exon 3 polymorphism reduces enzyme activity by approximately 50%, w...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2000

ISSN: 0021-9258

DOI: 10.1074/jbc.m001153200