Irreversible zymogens

Factor XIII. Factor XIII circulates in the blood as a zymogen composed of two pairs of different polypeptide chains designated A and B. Inert Factor XIII has a molecular weight of 350,000 daltons and is converted to its active transglutaminase form in the presence of thrombin and calcium. Activated Factor XIII, Xllla, induces an irreversible amide exchange reaction between the y-glutamine and S-lysine side chains of adjacent fibrin... 

For some enzymes, an inactive precursor called a zymogen is cleaved to form the active enzyme. Many proteolytic enzymes (proteases) of the stomach and pancreas are regulated in this way. Chymotrypsin and trypsin are initially synthesized as chymotrypsinogen and trypsinogen (Fig. 6-33). Specific cleavage causes conformational changes that expose the enzyme active site. Because this type of activation is irreversible, other... 

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. 

There are two general types of covalent modification of enzymes that regulate their activity. These are the irreversible activation of inactive enzyme precursors, the zymogens, and the reversible interconversion of active and inactive forms of an enzyme. 

Proteolysis is another way to control enzymatic activity, although unlike phosphorylation, the change in activity is irreversible. Many proteases are synthesized as inactive precursors (zymogens) that have to be cleaved by proteolysis to become active. These precursors include proteases that are secreted into digestive tracts or lysosomes, the catalytic active P subunits in the eukaryotic 20 S proteosome that are activated by... 

Proteolytic activation. The enzymes controlled by some of these mechanisms cycle between active and inactive states. A different regulatory motif is used to irreversibly convert an inactive enzyme into an active one. Many enzymes are activated by the hydrolysis of a few or even one peptide bond in inactive precursors called zymogens or proenzymes. 

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... 

Nonallosterlc mechanisms for regulating protein activity Include proteolytic cleavage, which irreversibly converts inactive zymogens into active enzymes, compartmentation of proteins, and signal-Induced modulation of protein synthesis and degradation. 

This includes both reversible changes like phosphorylation of specific serines in the enzymes of glycogen metabolism and irreversible changes like zymogen activation by proteolysis in digestion and blood clotting. These mechanisms are considered in more detail below. 

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. 

A zymogen is converted to the active form by the irreversible cleavage of specific peptide bonds in the protein. 

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