PURIFICATION AND INITIAL CHARACTERIZATION OF MICROSOMAL EPOXIDE HYDROLASE FROM THE HUMAN ADRENAL-GLAND

Microsomal epoxide hydrolase from the human adrenal gland was purified to a high degree of homogeneity in 10% overall yield using sequential chromatography on DE-52, FPLC Mono Q and FPLC Superose columns. The fact that the overall purification was only 7.3-fold indicates that approx. 14% of the total microsomal protein consisted of this enzyme, a uniquely high value. The human adrenal enzyme was found to resemble rat liver microsomal epoxide hydrolase closely in a number of respects, including molecular weight, N-terminal amino-acid sequence and response to low-molecular weight ligands. However, rabbit antibodies directed against human adrenal microsomal epoxide hydrolase crossreacted only weakly with the corresponding rat liver protein. The relatively high levels of microsomal epoxide hydrolase in the human adrenal gland suggest that this enzyme may be of particular importance in this tissue. However, very little cytochrome P-450-catalyzed metabolism of xenobiotics has been demonstrated in the human adrenal and our present results speak against the involvement of microsomal epoxide hydrolase in the steroid metabolism of this gland. Thus, the function of this enzyme in the human adrenal is enigmatic.