Role of Bile Acids in the Activation of Trypsinogen by Enterokinase: Disturbance of Trypsinogen Activation in Patients with Intrahepatic Biliary Atresia

Abstract

The effect of bile acids on the activation of trypsinogen by the soluble fraction of rat intestinal homogenates containing enterokinase (EC 3.4.4.8) was studied. Glycodeoxycholate, 2.5 mm, caused a 5.8-fold increase in the velocity of the activation process at low trypsinogen concentrations and a 2-fold increase of the maximal velocity of trypsinogen activation by enterokinase. Sodium taurocholate had a similar effect. The same concentration of glycodeoxycholate caused a decrease of the Michaelis constant for the enterokinase-catalyzed trypsinogen activation: Km was 0.09 mm in the absence of bile acids and fell to 0.015 mm in their presence. The total amount of trypsin formed from a known amount of trypsinogen was also augmented in the presence of bile acids. A similar result was obtained when human pancreatic juice was used as the source of trypsinogen and human small intestinal homogenates as the source of enterokinase. In three children with biliary atresia and no bile acids in the duodenal contents, abnormally low trypsin activities were found before and after stimulation of pancreatic function with pancreozymin-cholecystokinin and secretin. Chymotrypsin activity, however, was normal. Evidence was obtained that trypsinogen activation by enterokinase is incomplete in the absence of bile acids. It is concluded that in the rat and in man bile acids are important for a rapid and complete trypsinogen activation by enterokinase.