Mechanism of biliary secretion of membranous enzymes: bile acids are important factors for biliary occurrence of gamma-glutamyltransferase and other hydrolases.
To elucidate the mechanism of biliary occurrence of gamma-glutamyl transferase [EC 2.3.2.2] and alkaline phosphatase [EC 3.1.3.1], the effect of bile acids on the biliary level of these enzymes was studied in vivo and in vitro. Following intravenous administration of taurocholate, the activities of both enzymes in rat bile increased markedly with a concomitant increase in the excretion of the bile acid. The biliary levels of these enzymes increased to reach a maximum at 10-20 min after administration of the bile acid and decreased thereafter. Right-side-out oriented rat liver canalicular membrane vesicles which localize gamma-glutamyltransferase, aminopeptidase M and alkaline phosphatase on their outer surface (Inoue, M., Kinne, R., Tran, T., Biempica, L., & Arias, I.M. (1983) J. Biol. Chem. 258, 5183-5188) were prepared. Upon incubation of the vesicles with either intact or heat-treated bile samples, the membranous enzymes were released from the vesicles in a time-dependent manner. Incubation of these vesicles with physiological concentrations of taurocholate also solubilized these enzymes from the membranes. Affinity chromatographic analysis on concanavalin A-Sepharose revealed that the transferase thus solubilized retained the hydrophobic domain responsible for anchoring the enzyme to membrane/lipid bilayers. These results indicate that bile acid(s) excreted into the bile canalicular lumen solubilized these enzymes from the apical membrane surface of the biliary tract cells by their detergent action.
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000201:enzymology* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D018826:CD13 Antigens; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D008297:Male; D010190:Pancreatic Neoplasms / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013656:Taurocholic Acid / Q000378:metabolism / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000302:isolation & purification / Q000378:metabolism*
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D005723:gamma-Glutamyltransferase; D006867:Hydrolases; D000469:Alkaline Phosphatase; D000626:Aminopeptidases; D018826:CD13 Antigens