ABSTRACT
The role of enteropeptidase and trypsin in the process by which pancreatic proteolytic zymogens are converted into active enzymes has been investigated in the past, using purified enzymes and proenzymes of animal origin. In the present study, we wanted to study this process under conditions which come near to the physiological situation, which prevails in the human duodenum and upper small intestine. Patients and Methods: Duodenal contents were collected from 2 patients with intestinal enteropeptidase deficiency. The samples expressed no tryptic activity and were used as the source of zymogens. Enteropeptidase or trypsin was added to these samples and the process of zymogen activation was followed by measuring trypsin and chymotrypsin activities. Results: When exogenous trypsin was added to the duodenal contents of patients with enteropeptidase deficiency, having no tryptic activity, activation of intrinsic trypsinogen was not observed. When purified porcine or human enteropeptidase was added to the same samples of duodenal contents, this resulted in a rapid, dose-dependent activation of trypsinogen followed by the activation of chymotrypsinogen. Conclusion: The study underlines the key role of enteropeptidase in the cascade process, which leads to the presence of active proteolytic enzymes in the human small intestine. The results also explain why patients with congenital deficiency of enteropeptidase are unable to activate trypsinogen by alternative pathways and therefore suffer from a severe disturbance of protein digestion with failure to thrive at young age, hypoproteinemia, and anemia.
