Trypsinogen, protein digestion

Protein digestion occurs in two stages endopeptidases catalyse the hydrolysis of peptide bonds within the protein molecule to form peptides, and the peptides are hydrolysed to form the amino acids by exopeptidases and dipeptidases. Enteropeptidase initiates pro-enzyme activation in the small intestine by catalysing the conversion of trypsinogen into trypsin. Trypsin is able to achieve further activation of trypsinogen, i.e. an autocatalytic process, and also activates chymotrypsinogen and pro-elastase, by the selective hydro-... 

For trypsinogen activation, enteropeptidase (enterokinase, EC 3.4.21.9) [23] is a key enzyme for mammalian protein digestion. The selective cleavage site of trypsinogen by enteropeptidase initiates Lys6-Ile7 bond. Then trypsin (EC 3.4.21.4) activates other zymogens. Thus, the formation of trypsin by enteropeptidase is the master activation step. 

Dietary proteins, with very few exceptions, are not absorbed rather they must be digested into amino acids, or di- and tripeptides. Protein digestion begins in the stomach, where proenzyme pepsinogen is autocatalytically converted to pepsin A. Most proteolysis takes place in the duodenum via enzymes secreted by the pancreas, including trypsinogen, chymotrypsinogen and pro-carboxypeptidase A. These serine and zinc proteases are produced in the form of their respective proenzymes they are both endopeptidase and exopeptidase, and their combined action leads to the production of amino acids, dipeptides and tripeptides. 

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. 

The zymogen trypsinogen is cleaved to form trypsin by enteropeptidase (a protease, formerly called enterokinase) secreted by the brush-border cells of the small intestine. Trypsin catalyzes the cleavages that convert chymotrypsinogen to the active enzyme chymotrypsin, proelastase to elastase, and the procarboxypeptidases to the car-boxypeptidases. Thus, trypsin plays a central role in digestion because it both cleaves dietary proteins and activates other digestive proteases produced by the panaeas. 

The pancreas synthesizes and stores the zymogens in secretory granules. The pancreas also synthesizes a secretory trypsin inhibitor. The need for the inhibitor is to block any trypsin activity that may occur from accidental trypsinogen activation. If the inhibitor were not present, trypsinogen activation would lead to the activation of all of the zymogens in the pancreas, which would lead to the digestion of intracellular pancreatic proteins. Such episodes can lead to pancreatitis. 

The partly digested material passes next into the small intestine where the process of digestion is carried on by the substances present in the intestinal juice and the pancreatic juice. The latter contains amylopsin and trypsinogen. When the latter comes into contact with the enzyme enterokinase of the intestinal juice trypsin is formed. This enzyme, in the presence of the alkali in the intestinal juice, causes the hydrolysis of all forms of proteins. Unlike pepsin it causes the hydrolysis to proceed essentially to the complete splitting of the molecule to amino-acids. The juice secreted by the small intestine contains the proteolytic enzyme erepsin, which, with a few exceptions, induces the hydrolysis of only the derived proteins to amino-acids. 

A digestive enzyme formed in the small intestine when another enzyme, enterokinase, acts on trypsinogen, an inactive secretion of the pancreas. Trypsin cleaves polypeptides or proteins at peptide bonds adjacent to the amino acids aigin-ine or lysine. 

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