Cytosolic epoxide hydrolase in humans: development and tissue distribution

Area of Science:

• Biochemistry
• Pharmacology
• Toxicology

Background:

• Cytosolic epoxide hydrolase (sEH) is an enzyme involved in the metabolism of epoxides, which are reactive intermediates.
• Understanding sEH activity in different human tissues is crucial for assessing potential toxicological and pharmacological implications.

Purpose of the Study:

• To quantify and compare cytosolic epoxide hydrolase activity in various human fetal and adult tissues.
• To investigate the substrate specificity of sEH using trans-stilbene oxide.

Main Methods:

• Measurement of epoxide hydrolase activity using trans-stilbene oxide as a substrate.
• Analysis of enzyme activity in human adult livers (n=41), fetal livers (n=40), placentas (n=17), and fetal/adult lungs, kidneys, and gut.
• Quantification of trans-stilbene glycol formation rates (pmol/min per mg protein).

Main Results:

• Cytosolic epoxide hydrolase activity was detected in all investigated human fetal and adult tissues.
• Adult livers exhibited the highest activity (303.2 +/- 73.2 pmol/min per mg protein), significantly exceeding fetal liver activity (55.2 +/- 89.6 pmol/min per mg protein).
• Significant variations in sEH activity were observed across different fetal and adult extrahepatic tissues, with adult kidneys showing higher activity than adult lungs and urinary bladder.

Conclusions:

• Cytosolic epoxide hydrolase is widely distributed in human fetal and adult tissues, indicating its broad physiological relevance.
• Enzyme activity levels differ substantially between developmental stages and specific organs, suggesting tissue-specific roles and potential for differential drug metabolism or toxicity.
• The findings provide a foundational dataset for further research into the role of sEH in human health and disease.