Trypsinogen precursor

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. 

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... 

Some of the serine proteases are stored in the pancreas as inactive precursors that may be activated by proteolysis. Trypsinogen, for example, is converted to trypsin by the removal of the N-terminal hexapeptide on the cleavage of the bond between Lys-6 and Ile-7 by enterokinase. Chymotrypsinogen is activated by the tryptic cleavage of the bond between Arg-15 and He-16. (In this case, further proteolysis by the chymotrypsin that is released during the activation leads to the different forms of the enzyme—Figure 16.5.)... 

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. 

Zymogen. An inactive precursor of an enzyme. For example, trypsin exists in the inactive form trypsinogen before it is converted to its active form, trypsin. 

Enterokinase, a brush-border enzyme, activates trypsinogen into trypsin, which in tnm converts a number of precursor pancreatic proteases into their active forms. 

Similar examples of immunochemical isolation of inactive proteins may be found in the isolation of a precursor protein. Such situations are well documented for the zymogen systems such as trypsinogen-trypsin, chy-motrypsinogen-chymotrypsin, and proinsulin-insulin. 

Since the specific activities of pure porcine amylase (23), lipase (16), and trypsinogen (Section III, F) are known, approximate values for the percentage of the three enzymes in pig pancreatic juice can be estimated as stated above. These values are respectively 7.5, 2.5, and 24 % of the total proteins. By taking into account the specific activity of pure pig chymotrypsinogen A (Section III, D), a value of 14% is found for this class of precursors. However, the value is preliminary since the specific activity and the amount of the second chymotrypsinogen of pig are not yet known. 

Figures 10 and 11 show how porcine trypsinogen can be prepared in high yield by chromatography on CM-cellulose. The amino acid composition of this protein is given in Table III, with two sets of values for the bovine precursor. Analytical results have also been obtained with a commercial sample of bovine trypsin (123).

This was found to be the case (Viswanatha et al., 1960). In order to achieve the same degree of oxidation of tryptophan more NBS was required for trypsin than for trypsinogen (Fig. 23). A qualitative explanation may be that trypsin after rearrangement or contraction in the process of enzyme activation has become more compact and the four tryptophan units have become less accessible than in the precursor. 

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