Zymogen-enzyme transformations

Cross-Linkages Following Fibrin Clotting. The molecular events leading to formation of a stable fibrin clot include a cascade of interrelated zymogen-enzyme transformations as described above in Figure 2. The final proteolytic step in this process is the action of thrombin on fibrinogen as shown in Equation 6 ... 

Before turning to the strategy adopted in our work, a few of the characteristics of the two proteins are reviewed. The physical and chemical properties of these proteins have been discussed in detail 11, 14). As first shown by Langley, pepsin is present in its inactive form, pepsinogen, in the gastric mucosa. At acid pH, the zymogen is transformed by an autocat-alytic reaction into pepsin, a proteolytic enzyme with an activity optimum at pH 2.0 and a wide specificity 9, 10, 19). Pepsin is rapidly inactivated above pH 6.0, whereas pepsinogen is stable at neutrality 1 If). 

From the increase in the pro-rennet content of mucous membranes by dr3ung, it may be conduded that a dehydration takes place which transforms the rennet into pro-enzyme. Experiments of Effront have confirmed the retrogression of rennet into prorennet. It is to a phenomenon of the same order that must be attributed the diminution of activity which is observed in fresh rennet during the first two months of its preservation. (Note. — According to some authors the reaction zymogen— enzyme is considered non-reversible. — Ed.]... 

Schematic diagrams of the amino acid sequences of chymotrypsin, trypsin, and elastase. Each circle represents one amino acid. Amino acid residues that are identical in all three proteins are in solid color. The three proteins are of different lengths but have been aligned to maximize the correspondence of the amino acid sequences. All of the sequences are numbered according to the sequence in chymotrypsin. Long connections between nonadjacent residues represent disulfide bonds. Locations of the catalytically important histidine, aspartate, and serine residues are marked. The links that are cleaved to transform the inactive zymogens to the active enzymes are indicated by parenthesis marks. After chymotrypsinogen is cut between residues 15 and 16 by trypsin and is thus transformed into an active protease, it proceeds to digest itself at the additional sites that are indicated these secondary cuts have only minor effects on the enzymes s catalytic activity. (Illustration copyright by Irving Geis. Reprinted by permission.)...

Plasminogen activator is another protease that increases in many cell types after neoplastic transformation (20). This enzyme activates the zymogen plasminogen to the protease plasmin. Plasmin is a protease of broad specificity and high local proteolytic activity can be achieved in the vicinity of the transformed cells. 

Zymogens, also called proenzymes, are enzyme precursors. These proenzymes are said to be activated when (hey are transformed to the enzyme. Activation usually involves catalytic action by some proteolytic enzyme. Occasionally, the activators merely effect a reorganization of the tertiary structure (conformation) of the protein so that the groups involved within the reactive center become functional (i.c.. iin-mtLSked). 

Allosteric interactions control the behavior of proteins through reversible changes in quaternary structure, but this mechanism, effective though it may be, is not the only one available. A zymogen, an inactive precursor of an enzyme, can be irreversibly transformed into an active enzyme by cleavage of covalent bonds. 

The appearance and increase of cyclopenase activity (D 8.4.2) during conidiospore maturation in Penicillium cyclopium cannot be prevented by cycloheximide (D 3.3.7), an inhibitor of translation, in concentrations which suppress protein biosynthesis. This indicates that a proenzyme exists which is formed during an earlier stage of development. The mechanism of transformation of the cyclopenase proenzyme into active cyclopenase is still unclear. In similar cases, however, e.g., the activation of prochitin synthase in Saccharomyces cerevisiae and of a phenol oxidase zymogen (C 2.3.1) in the hemolymph of Calliphora larvae, the active enzyme is formed by proteolytic processing of a proteinogen. 

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