Exopeptidases, 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-... 

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. 

While all proteases convert proteins to amino acids, each enzyme acts on a particnlar section of the protein. Endopeptidases hydrolyze peptide bonds that are adjacent to specific amino acid side chains, thns converting long protein chains into many shorter peptides. The exopeptidases hydrolyze peptide bonds at either the carboxyl- or amino-terminal ends of these peptides. The endopeptidases, therefore, prodnce more snbstrates for the exopeptidases so that the rate of protein digestion accelerates almost like a chain reaction and then declines as the hydrolytic processes approach completion. 

The oligopeptides formed by the action of the endopeptidases are broken down into their constituent amino acids by the action of the exopeptidases. The carboxypeptidase of the pancreas splits amino acids one by one from the C-terminus so that, by the time they reach the absorbing cells of the small intestine, the dietary proteins have been converted into a mixture of amino acids and small peptides. The mucosal cells which contain both aminopeptidases and dipeptidase take up the small peptides which are then hydrolysed either within the brush border or in the layer immediately beneath it. Thus the final stages of protein digestion, like those of carbohydrates, are intracellular. Under normal circumstances no peptides pass across the mucosa to enter the bloodstream. 

Liver flukes also possess cathepsin C and LAP exopeptidases that are orthologous to the schistosome enzymes. These exopeptidases most likely complete the digestive process to yield free dipeptides and amino acids, respectively, from peptides generated by endoprote-olytic cysteine protease activity on host proteins. Both cathepsin C and LAP have been immunolocalized to gastrodermal cells (Carmona et al., 1994 Acosta et al., 1998 J.P. Dalton, unpublished data). 

In addition, in living systems, most biochemical reactions, including ATP hydrolysis, take place during the catalysis of enzymes. The catalytic action of enzymes allows the hydrolysis of proteins, fats, oils, and carbohydrates. As an example, one may consider proteases, enzymes that aid digestion by hydrolyzing peptide bonds in proteins. They catalyze the hydrolysis of interior peptide bonds in peptide chains, as opposed to exopeptidases, another class of enzymes, that catalyze the hydrolysis of terminal peptide bonds, liberating one free amino acid at a time. 

Most dietary proteins are known not to be absorbed in humans as intact forms. Instead, they are usually broken down into amino acids or di- and tripeptides first in the GI tract. The stomach secretes pepsinogen, which is converted to the active protease pepsin by the action of acid. Pepsins, which are most active at pH 2-3, hydrolyze partially digested dietary proteins. The partially digested dietary proteins are further broken down by proteolytic enzymes (peptidases) produced by the pancreas and secreted in the duodenum of the small intestine. The peptidases that break the internal peptide linkages are known as endopeptidases, whereas those that attack the terminal, or end, groups of amino acids are called exopeptidases. 

Carboxypeptidase A Bovine pancreas 34,500 1 C-terminal exopeptidase involved in digestion of proteins Zn functions in catalysis as a Lewis acid. 

In enzymic digestions, the structures of the released peptides will, of course, depend upon the specificity of the particular protease. Often the peptides exhibit a very undesirable bitter flavor. For example, Fujimaki et al. (22) have characterized seven bitter peptides in peptic hydrolysates of soybean proteins. Almost all the bitter peptides had leucine at the N or C termini, and the bitterness of the peptides could be reduced by treatment with exopeptidases such as carboxypeptidase A. 

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