Tissue distribution and ontogenic development

EPHX1 protein levels have been detected in a wide variety of tissues, including the liver, small intestine, kidney, lung, and urinary bladder. However, significant catalytic activities for styrene oxide hydrolysis were only demonstrated in the liver, lungs, kidneys, and gut.90 EPHX2 has been detected in all tissues studied except the bile ducts, glomeruli, and the thyroid, and appears to be most abundantly expressed in the hepatocytes, endocrine, proximal tubules in the kidney, and the lymph nodes.37 Expression of EPHX2 in the pituitary gland could be significant for drug metabolism because the pituitary lacks a blood-brain barrier but contains a high concentration of drug-metabolizing enzymes compared to other regions of the brain.

In the liver and adrenal gland, the activity of EPHX1 was three times higher than that observed in the kidney and lung and could be observed as early as 8 weeks' gestation (Table 4). At 22 weeks, EPHX1 activity had increased to about half that observed in adult liver. EPHX2 is also expressed in the fetus, although fewer ontogenic studies have focused on this isoform. EPHX2 activity was demonstrated as early as 14 weeks in fetal liver with no change in activity occurring with time.25 Adult hepatic activity of EPHX2 was fivefold higher than that observed in the fetus. However, additional studies are needed to examine the change in activity between 30 weeks' gestation and 30 years of age. EPHX2 is also observed in extrahepatic fetal tissue, including the kidney, adrenal glands, intestine, and lungs, but developmental expression in these tissues was less evident.90

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