Enzyme precursors

Complement is not a single protein but comprises a group of functionally linked proteins that interact with each other to provide mar of the effector functions of humoral immunity and inflammation. Most of the components of the system are present in the serum as proenzymes, i.e. enzyme precursors. Activation of a complement molecule occurs as a result of proteolytic cleavage of the molecule, which in itself confers proteolytic activity on the molecule. Thus, many components of the system serve as the substrate of a prior component and, in turn, activate a subsequent component. This pattern of sequential activation results in the system being called the complement cascade. ... 

Some Enzymes and Other Proteins Are Regulated by Proteolytic Cleavage of an Enzyme Precursor... 

The activation of enzyme precursors is likely to be of central importance. A significant fraction of the total SCCE present in the stratum corneum is in the form of inactive proenzyme.53,54 A change in the ratio of precursor to active enzyme may be expected to cause marked changes in the rate of corneodesmosomal degradation. In vitro pro-SCCE can be activated by pancreatic trypsin.39 As mentioned earlier SCTE has been suggested to act as an SCCE activator, but this remains to be elucidated. It is possible that SCCE is just one of a number of enzymes constituting a proteolytic cascade in the stratum corneum, in which one enzyme serves as activator of another enzyme. 

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. 

Enzyme Precursor Ion Scan Result (Da) Matching Sequence... 

Zymogens have been considered to be inactive precursors of enzymes and the activation process to involve the generation of a catalytic or substrate binding site or both 44). Recently, Behnke and Vallee (50) found that the spectral properties of cobalt-substituted procarboxypeptidase A closely resemble those of the cobalt enzyme. Since these spectra were believed to be peculiar to enzymatically active proteins (5i), they investigated the intrinsic catalytic activity of the cobalt zymogen. Remarkably, with certain substrates, cobalt procarboxypeptidase was found to have as much activity, and in some cases even more than the native enzyme. These observations, as well as those of others (52), have questioned the entire concept of zymogens as inactive enzyme precursors. 

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). 

Table V. Extracellular Calcium Enzymes and Enzyme Precursors...

Pepsinogen is called a zymogen or inactive enzyme precursor, which is activated by the enzymatic action of trace amounts of pepsin already present in the stomach. Activation is achieved by the removal of a small terminal peptide. Pepsin attacks the peptide bonds of amino acids possessing hydrophobic side groups, which reduces proteins to mbttures of smaller peptides. Other enzymatic hydrolases which are found in the small intestine are also secreted as zymogens, and are activated by similar processing. 

Three mechanisms of cellular control over enzyme activity exist. One method involves the synthesis of enzyme precursors called zymogens, which are activated when needed by the ceU. The second mechanism relies on the binding of small molecules (modulators), which increase or decrease enzyme activity. Genetic control of enzyme synthesis, the third method, regulates the amount of enzyme available. 

Figure 30-2. Representation of the chain conformation of the enzyme precursor chymotrypsinogen. The molecule has five disulfide cross-link bridges. The histidine and serine residues, drawn in black, form the active center of the molecule. The molecule transforms into the active enzyme, chymotrypsin, when the chain is broken at the position of the black rings to the left in the diagram. (After H. Neurath.)...

Bovine trypsinogen and chymotrypsinogen. These two digestive enzyme precursors have single chains of 229 and 245 residues, respectively. 

In secondary metabolism the intracellular location of enzymes, precursors, intermediates, and products is also strictly controlled. This makes possible... 

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