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 f act that the overall purification was only 7.3-fold indicates that app rox. 14% of the total microsomal protein consisted of this enzyme, a u niquely high value. The human adrenal enzyme was found to resemble rat liver microsomal epoxide hydrolase closely in a number of respects, i ncluding 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 w eakly with the corresponding rat liver protein. The relatively high le vels of microsomal epoxide hydrolase in the human adrenal gland sugges t that this enzyme may be of particular importance in this tissue. How ever, very little cytochrome P-450-catalyzed metabolism of xenobiotics has been demonstrated in the human adrenal and our present results sp eak against the involvement of microsomal epoxide hydrolase in the ste roid metabolism of this gland. Thus, the function of this enzyme in th e human adrenal is enigmatic.