Post-transcriptional regulation of human microsomal epoxide hydrolase

Elizabeth M. Laurenzana, Christopher Hassett, Curtis J. Omiecinski

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36 Scopus citations


Microsomal epoxide hydrolase (mEH) is a key biotransformation enzyme that is variably expressed in humans. Genetic polymorphisms in the mEH gene have been identified that result in amino acid substitutions in the corresponding enzyme. Results of expression analyses of the mEH allelic variants in vitro suggest that the mutations do not affect the specific activity of the mEH enzyme, but may alter post-transcriptional regulation of mEH. To identify potential post-transcriptional mechanisms that influence mEH expression, the translational efficiency, mRNA half-life, and protein half-life of mEH allelic variants were determined. Constructs encoding each of the four mEH alleles were transcribed in vitro and translated. No differences were detected in the rate of protein synthesis among the variant transcripts, indicating that the previously characterized coding region polymorphisms do not appear to affect translational efficiency. mEH variant RNA half-lives were determined in transfected COS-1 cells, but no differences in decay rates were apparent among the polymorphic constructs. Half-lives of the polymorphic mEH proteins were determined in transiently transfected COS-I cells treated with the protein synthesis inhibitor cycloheximide. Calculated protein half-lives were: Y113/H139, 15.2 h; H113/H139, 10.7 h, Y113/H139, 16.9 h and H113/R139, 16.0 h. The protein half-lives calculated for the polymorphic variants exhibited the same rank order as mEH protein and activity levels determined previously from expression experiments in vitro and therefore suggest that polymorphic amino acid substitution may result in altered protein stability. However, the differences noted were not statistically significant at the P < 0.05 level, and therefore additional study is required to firmly establish causative relationships.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
Issue number2
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)


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