Activation zymogen

BLOOD CLOTTING. The formation of blood clots is the result of a series of zymogen activations (Figure 15.5). The amplification achieved by this cascade of enzymatic activations allows blood clotting to occur rapidly in response to injury. Seven of the clotting factors in their active form are serine proteases ... 

Fig. 2.3. Schematic representation of consecutive zymogen activation reactions (cascade). Following initiation by a physiological signal ( ), the zymogens X, Y, and Z are sequentially activated. The resulting peptidases (Xa and Ya) are inactivated by specific inhibitors (Ix and Iy) to limit their action (modified from [20a]).

Stennicke, H. R., and Salvesen, G. S., 2000, Caspases - controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta 1477 299-306. 

The self-activating process for converting an inactive catalyst, I, to its active form, A. Such processes typically display a discernible lag-phase followed by accelerated conversion of I to A. Zymogen activation can display autocatalysis, as exemplified by the conversion of pepsinogen to active pepsin at low pH. Many growth processes can also be described via an autocatalysis curve. 

SOLVENT EFFECTS ZWiTTERGENTS DETERGENTS MICELLE ZWITTERION ZYMOGEN Zymogen activation,... 

During blood clot formation a complex cascade of zymogen activation occurs, whereby each currently activated zymogen activates the subsequent zymogen. For details one is referred to text books. 

Interactions between serine proteases are common, and substrates of serine proteases are usually other serine proteases that are activated from an inactive precursor [66]. The involvement of serine proteases in cascade pathways is well documented. One important example is the blood coagulation cascade. Blood clots are formed by a series of zymogen activations. In this enzymatic cascade, the activated form of one factor catalyzes the activation of the next factor. Very small amounts of the initial factors are sufficient to trigger the cascade because of the catalytic nature of the process. These numerous steps yield a large amplification, thus ensuring a rapid and amplified response to trauma. A similar mechanism is involved in the dissolution of blood clots. A third important example of the coordinated action of serine proteases is the intestinal digestive enzymes. The apoptosis pathway is another important example of coordinated action of other types of proteases. 

Several enzymes are synthesized as larger inactive precursor forms called proenzymes or zymogens. Activation of zymogens involves irreversible hydrolysis of one or more peptide bonds. 

Hyal-1, an acid-active lysosomal enzyme, was the first somatic hyaluronidase to be isolated and characterized.191,192 It is a 57 kDa single polypeptide glycoprotein that also occurs in a processed 45 kDa form, the result of two endoprotease reactions. The resulting two chains are bound by disulfide bonds. This is not a zymogen-active enzyme relationship, since the two isoforms have similar specific activities. Why two forms should occur is unknown. Only the larger form is present in the circulation, while both isoforms occur in urine,193 in tissue extracts, and in cultured cells. Why an acid-active hyaluronidase should occur in plasma is not clear. Some species do not have detectable enzymatic activity in their circulation,194 but an inactive 70 kDa precursor form of the enzyme is present in such sera, detectable by Western blot (L. Shifrin, M. Neeman, and R. Stern, unpubl. data). Hyal-1 is able to utilize HA of any size as substrate, and generates predominantly tetrasaccharides. 

Question What is the actual sequence of chemical events involved in zymogen activation ... 

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... 

Biochemical control systems (i.e., zymogens, activators, etc.). It is in this area that large advances should be forthcoming in the next decade or so. The sophisticated selective breakdowns of proteins to form functional products are among the most important biochemical control reactions found in tissues. 

Several vital processes rely on clan PA peptidases. Chief among them are blood coagulation and the immune response, which involve cascades of sequential zymogen activation. In both systems, the chymotrypsin-fold peptidase domain is combined with one more associated protein domains, including apple, CUB, EGF, fibronectin, kringle, sushi, and von Willebrand factor domains. These protein domains are on the N-terminus as an extension of the propeptide segment of the peptidase. Such a trend of N-terminal-associated domains in the SIA peptidase family is common across all forms of life. The domain architecture pairs well with the zymogen activation mechanism, which liberates the proper N-terminus to enable catalytic activity. Often, the associated protein domains remain attached to... 

Blood Clotting Is Accomplished by a Cascade of Zymogen Activations... 

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.

Zymogen activation. When very low concentrations of pepsinogen are added to acidic media, how does the halftime for activation depend on zymogen concentration ... 

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