Specific expression of ES46.5K, a novel microsomal esterase, in the mouse liver and its catalytic activity for xenobiotic amide and esters

• Published in: Life sciences (1973) 1997, Vol.61 (14), p.1389-1394
• Main Authors: Watanabe, Kazuhito, Kayano, Yuichiro, Matsunaga, Tamihide, Yamamoto, Ikuo, Yoshimura, Hidetoshi
• Format: Article
• Language: English
• Subjects: Adolescent; Amides - metabolism; Amidohydrolases - metabolism; Animals; Blotting, Western; Carboxylic Ester Hydrolases - metabolism; Catalysis; ES46.5K; Esters - metabolism; Female; Guinea Pigs; Humans; Macaca mulatta; Male; Mice; microsomal esterase; Microsomes, Liver - enzymology; Rabbits; Rats; Rats, Sprague-Dawley; Species Specificity; xenobiotic ester metabolism; Xenobiotics - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(97)00684-X

ES46.5K, a novel esterase, was found in mouse hepatic microsomes. The enzyme catalyzed hydrolysis of 2-acetylaminofluorene and cannabinoid esters. In latter case, the enzyme regioselectively hydrolyzed acetates of 11-hydroxy-δ 8-tetrahydrocannabinol. Western immunoblotting analysis demonstrated that none of immune-reactive proteins against ES46.5K were present in hepatic microsomes from rats, guinea-pigs, monkeys and humans. Rabbit hepatic microsomes contained an immuno-reactive protein, although molecular weight of the protein was rather high (50 kDa) by SDS-PAGE. Esterase activity stained after PAGE demonstrated that ES46.5K retained at origin. Hepatic microsomes of above animal species contained several activity bands on the PAGE, while only mouse hepatic microsomes exhibited significant activity at origin. In mice, liver was only an organ containing ES46.5K by analyzing Western immunoblotting. These results indicate that distribution of ES46.5K is quite different from known carboxylesterases, and suggest that the enzyme has some role in the biotransformation of xenobiotic amide and esters.