Procarboxypeptidase inactive precursor

The inactive precursors are called trypsinogen, pepsinogen, chymotrypsino-gen, and procarboxypeptidase. These precursors are converted to the active enzymes by hydrolytic cleavage of a few specific peptide bonds under the influence of other enzymes (trypsin, for example, converts chymotrypsinogen to chymotrypsin). The digestive enzymes do not appear to self-destruct, probably because they are so constructed that it is sterically impossible to fit a part of one enzyme molecule into the active site of another. In this connection, it is significant that chymotrypsin attacks denatured proteins more rapidly than natural proteins with their compact structures of precisely folded chains. 

Carboxypeptidases A and B are formed by the hydrolytic action of trypsin upon inactive precursors, procarboxypeptidases. These zymogens are synthesized in the pancreas from which they can be isolated (88). Depending on the preparation method, different forms of carboxypeptidase A are produced, varying in the N-terminal region (89). 

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. 

In 1936, Anson (127) crystallized what is now called carboxypeptidase A from autolyzed bovine pancreas and noted that fresh pancreas did not contain the active enzyme, but an inactive precursor now named procarboxypeptidase A. It has been reported in the preceding sections that pancreatic juices of other species also contain large amounts of procarboxypeptidase A which can be separated by chromatography on DEAE-cellulose at pH 8.0 in a buffer of increasing molarity. 

Carboxypeptidaae. Carboxypeptidase occurs in extracts of pancreas. The pancreas contains an inactive precursor of the enzyme, a zymogen. In the case of carboxypeptidase the precursor has been partially purified. The accumulation of zymogens seems to be characteristic for those proteolytic enzymes that are secreted. In neutral solutions procarboxypeptidase is converted to active carboxypeptidase by the action of other enzymes present in the crude extracts. The mechanism of this activation is not completely known, although it appears that the reaction involves splitting of peptide bonds by other proteolytic enzymes. 

Procarboxypeptidase is the inactive precursor of the pancreatic exopeptidase which hydrolyses the peptide bonds joining the amino acid in the C-terminal position to the rest of the chain. 

Carboxypeptidases may be found in the kidney and spleen, but occur in the digestive juice in particularly large amounts. One carboxypeptidase has been purified to the crystalline stage it has a molecular weight of 34,000 and contains zinc. It is secreted from the pancreas in the form of an inactive precursor (procarboxypeptidase) with a molecular weight of 90,000. 

The proteases are secreted as inactive zymogens the active site of the enzyme is masked by a small region of its peptide chain, which is removed by hydrolysis of a specific peptide bond. Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells trypsin can then activate chymotrypsinogen to chymotrypsin, proelas-tase to elastase, procarboxypeptidase to carboxypepti-dase, and proaminopeptidase to aminopeptidase. 

Propnrteins inactive protein precirtsots, which are activated by the removal (a highly specific reaction) of a peptide sequence. Exarrtples are various Secretory enzymes (see) (procarboxypeptidase, proelas-tase, prothrombin, etc.) hormone precursors (proinsulin, proparathormone, etc.), peptide toxins (promelli-tin, etc.) and Zymogens (see). 

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