Digestive system zymogens

A different type of covalent regulation of enzyme activity is the enzyme-catalysed activation of inactive precursors of enzymes (zymogens) to give catalytically active forms. The best examples are the digestive enzymes, e.g. trypsin. Proteolytic enzymes would digest the inside of the cells that produce the enzyme, so they are produced in an inactive form which is activated to the true enzyme once they have entered the digestive system of the animal. 

A zymogen is an inactive protein that is converted to an active protein by specific proteolysis (hydrolysis of peptide bonds). This mechanism is used when enzymes must be stored in an inactive form ready for rapid activation, as in blood clotting, or when enzymes must be transported in an inactive state from their site of synthesis to their site of action. The use of zymogens by the digestive system is an excellent example of the latter situation. Digestion involves breakdown of the proteins, and other molecules, in food without damaging the host tissues (Fig. 9.1). 

FIGURE 23-24 The endocrine system of the pancreas. In addition to the exocrine cells (see Fig. 18—3b), which secrete digestive enzymes in the form of zymogens, the pancreas contains endocrine tissue, the islets of Langerhans. The islets contain a, /3, and S cells (also known as A, B, and D cells, respectively), each cell type secreting a specific polypeptide hormone. 

Specialized histochemical, immunohistochemical (IHC), and other tissue section-based molecular techniques (e.g., in situ hybridization (ISH)) can be used to better characterize the nature of the injury, cell types affected and its relationship to test article distribution and/or its intended target. The distribution of digestive enzymes or their proenzymes in the zymogen granules of acinar cells can be demonstrated using IHC markers for trypsin, chymotrypsin, carboxypeptidases A and B, lipase, amylase, elastase, DNase, and RNase (Cattley et al., 2013). Cytokeratin IHC markers can be used to differentiate epithelial components of the pancreas, most notably the cells of the ductal system. Amylase and MISTI have used been as IHC markers to confirm acinar cell differentiation experimentally. Trypsinogen activation peptide (TAP), a peptide released from trypsinogen when trypsin is activated, can be used as an IHC marker for intracellular activation... 

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