Pancreatic zymogens

RC Delisle, U Hopfer. (1986). Electrolyte permeabilities of pancreatic zymogen granules Implications for pancreatic secretion. Am J Physiol 250 G489-G496. 

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. 

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.

Gaisano HY, Sheu L, Foskett JK et al. (1994) Tetanus toxin light chain cleaves a vesicle-associated membrane protein (VAMP) isiform 2 in rat pancreatic zymogen granules and inhibits enzyme secretion. J. Biol. Chem. 269 17062-6. 

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. 

Pancreatic zymogen granule protein GP2 Paraoxonase parathyroid hormone Parathyroid hormone-related protein PASP... 

Our current knowledge of the intracellular sequence of events regarding the formation of pancreatic zymogen granules is largely a result of the investigative efforts of Palade and his co-workers. In a classic electron microscopic radioautographic study, Caro and Palade (1964) followed the uptake and intracellular distribution of a pulse label of tritiated leucine. The label was administered intravenously to rats sub-... 

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