0000000000014267

AUTHOR

Michael Knehr

showing 4 related works from this author

Rat and human liver cytosolic epoxide hydrolases: evidence for multiple forms at level of protein and mRNA.

1990

Two forms of human liver cytosolic epoxide hydrolase (cEH) with diagnostic substrate specificity for trans-stilbene oxide (cEHTSO) and cis-stilbene oxide (cEHCSO) have been identified, and cEHCSO was purified to apparent homogeneity. The enzyme had a monomer molecular weight of 49 kDa and an isoelectric point of 9.2. Pure cEHCSO hydrolyzed CSO at a rate of 145 nmole/min/mg. TSO was not metabolized at a detectable level, and like cEHTSO, the enzyme was about three times more active at pH 7.4 than at pH 9.0. Unlike cEHTSO, cEHCSO was efficiently inhibited by 1 mM 1-trichloropropene oxide (90.5%) and 1 mM STO (92%). Similarly, liver cEH purified 541-fold from fenofibrate induced Fischer 344 ra…

Health Toxicology and MutagenesisBiologyCytosolSpecies SpecificityWestern blotmedicineAnimalsHumansRNA MessengerEpoxide hydrolaseEpoxide Hydrolaseschemistry.chemical_classificationmedicine.diagnostic_testImmunochemistryPublic Health Environmental and Occupational HealthDNAMolecular biologyRatsMolecular WeightBlotIsoelectric pointEnzymeLiverBiochemistrychemistryPolyclonal antibodiesMicrosomal epoxide hydrolaseEpoxide Hydrolasesbiology.proteinResearch ArticleEnvironmental Health Perspectives
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Isolation and characterization of a cDNA encoding rat liver cytosolic epoxide hydrolase and its functional expression in Escherichia coli.

1993

A cDNA of 1992 base pairs encoding the complete rat liver cytosolic epoxide hydrolase has been isolated using a polymerase chain reaction-derived DNA fragment (Arand, M., Knehr, M., Thomas, H., Zeller, H. D., and Oesch, F. (1991) FEBS Lett. 294, 19-22) known to represent the 3'-end of the cytosolic epoxide hydrolase mRNA. Sequence analysis revealed an open reading frame of 1662 nucleotides corresponding to 554 amino acids (M(r) = 62,268). The DNA sequence obtained did not display significant homology to the sequences of microsomal epoxide hydrolase or leukotriene A4 hydrolase or to any other DNA included in the EMBL Data Bank (release 32). On Northern blotting of rat liver RNA, a single mRN…

Epoxide hydrolase 2Male1303 BiochemistryBase pairMolecular Sequence DataRestriction Mapping10050 Institute of Pharmacology and Toxicology610 Medicine & healthBiologyBiochemistryLeukotriene-A4 hydrolase1307 Cell BiologyRats Sprague-Dawleychemistry.chemical_compoundCytosolFenofibrateComplementary DNA1312 Molecular BiologyEscherichia coliAnimalsAmino Acid SequenceCloning MolecularEpoxide hydrolaseMolecular BiologyPeroxisomal targeting signalEpoxide HydrolasesBase SequenceCell BiologyDNABlotting NorthernMolecular biologyRatschemistryBiochemistryLiverMicrosomal epoxide hydrolase570 Life sciences; biologyDNAThe Journal of biological chemistry
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An impaired peroxisomal targeting sequence leading to an unusual bicompartmental distribution of cytosolic epoxide hydrolase

1991

AbstractTo gain an understanding of the mechanism by which the subcellular distribution of cytosolic epoxide hydrolase (cEH) is directed, we have analyzed the carboxy terminal region of rat liver cEH by means of cDNA cloning to define the structure of its possible peroxisomal targeting sequence (PTS). Purified cEH was subjected to peptide analysis following endoproteinase Glu-C digestion and HPLC-separation of the fragments. The obtained sequence information was used to perform PCR experiments resulting in the isolation of a 680 bp cDNA clone encoding the carboxy terminus of cEH. The deduced amino acid sequence displays a terminal tripeptide Ser-Lys-Ile which is highly homologous to the PTS…

MaleSignal peptidePTSanimal structures1303 BiochemistryMolecular Sequence DataBiophysics10050 Institute of Pharmacology and Toxicology610 Medicine & healthTripeptideProtein Sorting SignalsBiologyMicrobodiesBiochemistryAmino acid sequence1307 Cell BiologyCytosol1315 Structural Biology1311 GeneticsStructural BiologyComplementary DNAGenetics1312 Molecular BiologyAnimalsCloning MolecularEpoxide hydrolaseMolecular BiologyPeptide sequenceEpoxide Hydrolaseschemistry.chemical_classificationBase SequencecDNA sequenceDNACell BiologyPeroxisomeMolecular biologyRatsIsoenzymesCytosolPCREnzymeLiverchemistryBiochemistrycEH570 Life sciences; biologyPeptide analysis1304 Biophysics
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Epoxide Hydrolase Isoenzymes and their Individual Contribution to the Control of Toxic Metabolites

1991

Epoxides are highly strained three membered cyclic ethers which are formed in vivo by the microsomal cytochrome P450 dependent monooxygenases as intermediates of several important biosynthetic pathways (leukotriene A4, squalene 2, 3-oxide) and as metabolites of numerous xenobiotic compounds containing olefinic or aromatic double bonds. Further transformation of these epoxides may occur by either, rearrangement to phenols, aliphatic aldehydes, or ketones; by cytochrome P450 dependent reduction to the parent compound; or by spontaneous or enzymatic conjugation to gluta-thione. Epoxides may also bind covalently to cellular nucleophiles, such as proteins and nucleic acids thus eliciting carcino…

chemistry.chemical_compoundbiologychemistryBiochemistryLeukotriene A4Microsomal epoxide hydrolaseNucleic acidbiology.proteinCytochrome P450MonooxygenaseEpoxide hydrolaseXenobioticCarcinogen
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