Pancreatic zymogens, activation

KW Gasser, J DiDomineco, UH Hopfer. (1988). Secretagogues activate chloride transport pathways in pancreatic zymogen granules. Am J Physiol 254 G93-G99. 

AP is initiated by premature activation of pancreatic zymogens (inactive enzymes) within the acinar cells, pancreatic ischemia, or pancreatic duct obstruction. 

Release of zymogens The release and activation of the pancreatic zymogens is mediated by the secretion of cholecystokinin and secretin, two polypeptide hormones of the digestive tract (see p. 174). 

Fig. 5. The central role of trypsin in activating the pancreatic zymogens.

The enzyme that initiates the activation of all major pancreatic zymogens in the small intestine is... 

In the duodenum, the pancreatic zymogens, trypsinogen, chymotrypsinogen, proelastase and procarboxypeptidase are converted into active enzymes by enteropeptidase and trypsin, as shown in Fig. 15-6. The activation of all the zymogens involves cleavage of peptide bonds and removal of peptides, enabling conformational changes and formation of a functional active site. 

H-5) Pancreatitis. Pancreatic lipase is a lipolytic enzyme that releases fatty acids from glycerides. It, as well as proteolytic enzymes produced by the pancreas, are normally, as a cell-protective measure, kept in inactive (zymogen) form in h.e pancreatic cell. Pancreatitis can activate these enzymes with resultant pancreatic damage. 

Figure 10.34. Zymogen Activation by Proteolytic Cleavage. Enteropeptidase initiates the activation of the pancreatic zymogens by activating trypsin, which then activates other zymogens. Active enzymes are shown in yellow zymogens are shown in orange.

D) Trypsin activates enteropeptidase, which is needed to activate the other pancreatic zymogens. 

Ans. The pancreas secretes an array of proteolytic zymogens which must be activated in the small intestine by trypsin, itself secreted as a pancreatic zymogen, trypsinogen. It is pKJSsible for this zymogen to be prematurely activated to trypsin within the pancreas. However, the pancreas also secretes a specific trypsin inhibitor which binds strongly to and inactivates any trypsin prematurely activated. 

Explain why the new carboxyl-terminal residues of the polypeptide chains produced during the activation of pancreatic zymogens are usually Arg or Lys. 

Because trypsin is the common activator of the pancreatic zymogens, its specificity for Arg-X and Lys-X peptide bonds wifi produce Arg and Lys carboxyf-terminaf residues. 

Autolysis of the pancreas can occur when zymogens are activated in the pancreas before being released into the duodenum. Acute pancreatitis can result from the initial injury to the zymogen-producing cells, which is followed by neutrophil invasion of the pancreas, and that ends in further activation of enzymes within the pancreas. This cascade of events can be destructive to the pancreas and harmful to the patient. 

Chymotrypsin has also been utilized to promote debridement, as well as the reduction of soft tissue inflammation. It is also used in some opthalmic procedures, particularly in facilitating cataract extraction. It is prepared by activation of its zymogen, chymotrypsinogen, which is extracted from bovine pancreatic tissue. 

To prevent self-digestion, the pancreas releases most proteolytic enzymes into the duodenum in an inactive form as proenzymes (zymogens). Additional protection from the effects of premature activation of pancreatic proteinases is provided by proteinase inhibitors in the pancreatic tissue, which inactivate active enzymes by complex formation (right). 

Promotes self-cleavage of pancreatic proteases from their inactive zymogen forms to active enzymes. 

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