Inhibitory Effect of Bile Acids on the Activity of Human -Glucuronidase at Its Optimal pH

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Abstract
The effect of bile acids on .beta.-glucuronidase activity was studied with centrifuged and dialyzed urines as the source of enzyme and phenolphthalein glucuronide as the substrate. The enzyme activity was measured at 56.degree. in acetate buffer pH 5.2. All unconjugated bile acids tested showed no effect on the enzyme activity, primarily due to their low solubility in water. The glycine and taurine conjugates of cholic acid showed no significant influence on the enzyme. Conjugated deoxycholic and chenodeoxycholic acids were profoundly inhibitory to the enzyme within the physiological range of concentration in bile. Kinetic studies revealed that taurine conjugates of these 2 bile acids were pure competitive inhibitors of the enzyme for the substrate; their glycine conjugates exhibited a mixed competitive and noncompetitive inhibition. Both urine and bile enzymes have an identical narrow pH activity curve; pH and bile acids are 2 major determinants of .beta.-glucuronidase activity in bile, and their alteration may predispose to bilirubin pigment gallstone formation.