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Human liver cytosolic epoxide hydrolases
L Schladt1, H Thomas, R Hartmann
1Institut für Toxikologie, Universität Mainz, Federal Republic of Germany.
European Journal of Biochemistry
|October 1, 1988
Summary
This study characterized human liver epoxide hydrolases, purifying cytosolic cis-stilbene oxide hydrolase (cEHCSO). Researchers compared substrate hydrolysis and enzyme properties, revealing distinct characteristics for microsomal and cytosolic forms, and identifying cEHCSO
Area of Science:
- Biochemistry
- Enzymology
- Pharmacology
Background:
- Epoxide hydrolases are crucial enzymes involved in xenobiotic and endogenous epoxide metabolism.
- Human liver epoxide hydrolases play a significant role in detoxification pathways.
- Understanding the distinct properties of different epoxide hydrolase isoforms is essential for drug development and toxicology.
Purpose of the Study:
- To characterize human liver epoxide hydrolases, focusing on substrate specificity and enzymatic properties.
- To purify and investigate the biochemical characteristics of cytosolic cis-stilbene oxide hydrolase (cEHCSO).
- To compare human liver epoxide hydrolases with their rat counterparts.
Main Methods:
- Purification of cytosolic cis-stilbene oxide hydrolase (cEHCSO) to homogeneity.
- Substrate hydrolysis assays using various styrene oxides and phenylmethyloxiranes with microsomal and cytosolic fractions.
- Isoelectric focusing, anion-exchange chromatography, gel filtration, and immunochemical analyses.
Main Results:
- Differential substrate hydrolysis patterns were observed between microsomal and cytosolic epoxide hydrolases.
- Purified cEHCSO exhibited distinct properties, including a high isoelectric point (9.2) and molecular mass (49 kDa).
- Immunochemical analysis indicated a relationship between human cEHCSO and rat liver microsomal epoxide hydrolase, but not rat cytosolic forms.
Conclusions:
- Human liver possesses distinct microsomal and cytosolic epoxide hydrolases with differing substrate specificities and biochemical properties.
- Cytosolic cis-stilbene oxide hydrolase (cEHCSO) is a well-defined enzyme with characteristics similar to rat liver microsomal epoxide hydrolase.
- Cytosolic trans-stilbene oxide hydrolase (cEHTSO) is immunochemically distinct from rat epoxide hydrolases, suggesting species-specific differences.