Proteinases, zymogens

The pancreatic enzyme it stored and secreted as a proenzyme with an additional seven residues at the N-tcmiinus, The proenzyme serves, like the other pancreatic proteinase zymogens, to prevent aotodigestion of the pancreatic cells. Upon secretion into the gastrointestinal tract, trypsin cleaves off these seven residues to produce the enzymatic form with full activity on insoluble substrates. On monomeric substrates, however, there is little difference between the catalytic activity of the proenzyme and of the activated enzyme [34],... 

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). 

Normally, thrombin is present in the blood as an inactive proenzyme (see p. 270). Prothrombin is activated in two different ways, both of which represent cascades of enzymatic reactions in which inactive proenzymes (zymogens, symbol circle) are proteolytically converted into active proteinases (symbol sector of a circle). The proteinases activate the next proenzyme in turn, and so on. Several steps in the cascade require additional protein factors (factors 111, Va and Villa) as well as anionic phospholipids (PL see below) and Ca "" ions. Both pathways are activated by injuries to the vessel wall. 

The digestive enzymes trypsin, chymotrypsin, elastase, and proteinase E are related serine proteases. All three are synthesized in the pancreas which secretes 5-10 g per day of proteins, mostly the inactive proenzymes (zymogens) of digestive enzymes.191,192... 

Pepsin (EC 3.4.23.1) is a typical aspartic proteinase produced in the gastric mucosa of vertebrates as a zymogen form [10], This enzyme has been extensively characterized, and its three-dimensional structure has been determined at high resolution. Porcine pepsin, in particular, has been studied as model to analyze the structure-function relationship of the aspartic proteinases. Although the aspartic proteinases including mammalian and fungal enzymes are quite similar in their three-dimentional structures, there are drastic differences in the catalytic properties, especially in substrate specificities. 

There are a number of potential ways by which ROIs released from inflammatory cells may also indirectly effect structure and function of connective tissue. Oxidants may compromise connective tissue integrity through the activation of proteinases secreted in latent form (i.e. as zymogens) (see Fig. 2). 

Although the favoured candidate for physiological activation of MMPs is through the classical zymogen activation by proteolysis, oxidative activation may be critical under certain pathological conditions (e.g., specifically at inflammatory foci) (see Fig. 2). Since there is considerable variation in the ability of proteinases to activate MMPs, the oxidative route may be more... 

Proteinase precursors, also called zymogens or proenzymes, become catalytically active enzymes upon specific proteolytic cleavage. The precursor molecules circulate as inactive forms that do not exhibit enzymatic activity. The activation processes are irreversible. Extensive structural similarities are found among all proteinase precursors. The regions of the molecules that express proteinase activity after activation are found in the C-terminal one-half to one-third of each molecule. The portion of each precursor... 

A multitude of bacterial pathogen proteins have been characterized and crystallized recently. Amongst them, cofactors of human serine proteinases or their zymogens... 

Hiramatsu R, Aikawa J, Horinouchi S et al. (1989) Secretion by yeast of the zymogen form of Mucor rennin, an aspattic proteinase of Mucor pusillus, and its conversion to the mature form. The J Biol Chem 264(28) 16862-16866... 

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