SPECIFIC EXPRESSION OF ES46.5K, A NOVEL MICROSOMAL ESTERASE, IN THE MOUSE-LIVER AND ITS CATALYTIC ACTIVITY FOR XENOBIOTIC AMIDE AND ESTERS

ES46.5K, a novel esterase, was found in mouse hepatic microsomes. The enzyme catalyzed hydrolysis of 2-acetylaminofluorene and cannabinoid e sters. In latter case, the enzyme regioselectively hydrolyzed acetates of 11-hydroxy-Delta(8)-tetrahydrocannabinol. Western immunoblotting a nalysis demonstrated that none of immune-reactive proteins against ES4 6.5K were present in hepatic microsomes from rats, guinea-pigs, monkey s and humans. Rabbit hepatic microsomes contained an immune-reactive p rotein, although molecular weight of the protein was rather high (50 k Da) by SDS-PAGE. Esterase activity stained after PAGE demonstrated tha t ES46.5K retained at origin. Hepatic microsomes of above animal speci es contained several activity bands on the PAGE, while only mouse hepa tic microsomes exhibited significant activity at origin. In mice, live r was only an organ containing ES46.5K by analyzing Western immunoblot ting. These results indicate that distribution of ES46.5K is quite dif ferent from known carboxylesterases, and suggest that the enzyme has s ome role in the biotransformation of xenobiotic amide and esters.