Inhibition of rat liver microsomal bilirubin UDP-glucuronosyltransferase by ursodeoxycholic acid. 1994

E J Sánchez Pozzi, and M G Luquita, and V A Catania, and E A Rodríguez Garay, and A D Mottino
Instituto de Fisiología Experimental, CONICET-U.N.R. Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.

Ursodeoxycholic acid and its endogenous metabolite tauroursodeoxycholic acid inhibited in vitro the microsomal bilirubin UDP-glucuronosyltransferase from rat liver. The magnitude of the inhibition correlated well with the loss of integrity of microsomal vesicles, suggesting that bile salts needed to reach the lumen to exert their inhibitory effects. The endogenous bile acids cholic acid, chenodeoxycholic acid and deoxycholic acid also exhibited inhibitory effects on bilirubin glucuronidation in digitonin-disrupted microsomes. Ursodeoxycholic acid inhibitory capacity was similar to that of chenodeoxycholic acid and deoxycholic acid but greater than that of cholic acid, the major endogenous bile salt. Kinetic studies, performed in detergent-activated preparations, showed that the inhibitions produced by ursodeoxycholic and tauroursodeoxycholic acids were competitive toward both bilirubin and UDP-glucuronic acid. The estimated Ki(app) for both substrates did not differ statistically between ursodeoxycholic and tauroursodeoxycholic acids. Both bile salts were weak inhibitors toward bilirubin but rather strong inhibitors toward UDP-glucuronic acid.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008566 Membranes Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. Membrane Tissue,Membrane,Membrane Tissues,Tissue, Membrane,Tissues, Membrane
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D010744 Phosphoric Monoester Hydrolases A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D004072 Digitonin A glycoside obtained from Digitalis purpurea; the aglycone is digitogenin which is bound to five sugars. Digitonin solubilizes lipids, especially in membranes and is used as a tool in cellular biochemistry, and reagent for precipitating cholesterol. It has no cardiac effects. Digitin
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001647 Bile Acids and Salts Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile

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