Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency.

The activities of pancreatic enzymes decrease during their passage from the duodenum to the terminal ileum, but degradation rates of individual enzymes are different. Whereas lipase activity is lost most rapidly, proteases and amylase are more stable. The mechanism by which lipase activity is destroyed is proteolysis, mainly by the action of chymotrypsin. This mechanism is also operative in patients with chronic exocrine pancreatic insufficiency. It explains why fat malabsorption develops earlier compared with protein or starch malabsorption. The substitution of lipase is also more difficult than that of other enzymes, because it is more rapidly destroyed by proteases. Conversely, inactivation of proteases improves intraluminal activity of lipase not only in healthy individuals but also in patients with chronic pancreatitis. Other factors that contribute to problems in lipase substitution therapy include acid-peptic destruction of unprotected enzyme preparations and unphysiological particle sizes of enteric-coated capsules or pellets. Recent data suggest that the adaptation of the diameter of enteric-coated pancreatin micropellets into the range that permits gastric emptying in synchronicity with the meal improves their digestive efficacy.