Intestinal Exopeptidase

There are two main classes of proteolytic digestive enzymes (proteases), with different specificities for the amino acids forming the peptide bond to be hydrolyzed. Endopeptidases hydrolyze peptide bonds between specific amino acids throughout the molecule. They are the first enzymes to act, yielding a larger number of smaller fragments, eg, pepsin in the gastric juice and trypsin, chymotrypsin, and elastase secreted into the small intestine by the pancreas. Exopeptidases catalyze the hydrolysis of peptide bonds, one at a time, fi"om the ends of polypeptides. Carboxypeptidases, secreted in the pancreatic juice, release amino acids from rhe free carboxyl terminal, and aminopeptidases, secreted by the intestinal mucosal cells, release amino acids from the amino terminal. Dipeptides, which are not substrates for exopeptidases, are hydrolyzed in the brush border of intestinal mucosal cells by dipeptidases. 

The end product of the action of endopeptidases and exopeptidases is a mixmre of free amino acids, di- and tripeptides, and oligopeptides, all of which are absorbed. Free amino acids are absorbed across the intestinal mucosa by sodium-dependent active transport. There are... 

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-... 

These proteolytic enzymes are all endopeptidases, which hydrolyse links in the middle of polypeptide chains. The products of the action of these proteolytic enzymes are a series of peptides of various sizes. These are degraded further by the action of several peptidases (exopeptidases) that remove terminal amino acids. Carboxypeptidases hydrolyse amino acids sequentially from the carboxyl end of peptides. They are secreted by the pancreas in proenzyme form and are each activated by the hydrolysis of one peptide bond, catalysed by trypsin. Aminopeptidases, which are secreted by the absorptive cells of the small intestine, hydrolyse amino acids sequentially from the amino end of peptides. In addition, dipeptidases, which are structurally associated with the glycocalyx of the entero-cytes, hydrolyse dipeptides into their component amino acids. 

Proteins are first denatured by the stomach s hydrochloric acid (see p. 270), making them more susceptible to attack by the endopeptidases (proteinases) present in gastric and pancreatic juice. The peptides released by endopeptidases are further degraded into amino acids by exopeptidases. Finally, the amino acids are resorbed by the intestinal mucosa in cotransport with Na"" ions (see p. 220). There are separate transport systems for each of the various groups of amino acids. 

The luminal surface of the intestine contains aminopeptidase—an exopeptidase that repeatedly cleaves the N-terminal residue from oligopeptides to produce free amino acids and smaller peptides. 

Carboxyl-terminal amino acid residues can be identified using exopeptidases called carboxypeptidase A and B. These are enzymes normally found in mammalian small intestine. Carboxypeptidase A causes the removal of amino acids, other than proline and basic amino acids, from the C terminus of peptides and proteins. The C-terminal amino acid appears first, followed by the next in line, and so forth. Carboxypeptidase B removes basic amino acids from the C termini of peptides and proteins. 

Protein digestion begins in the stomach, where a proenz5nme called pepsinogen is secreted, autocatalytically converted to Pepsin A, and used for the first step of proteolysis. However, most proteolysis takes place in the duodenum as a consequence of enzyme activities secreted by the pancreas. All of the serine proteases and the zinc peptidases of pancreatic secretions are produced in the form of their respective proenzymes. These proteases are both endopeptidase and exopeptidase, and their combined action in the intestine leads to the production of amino acids, dipeptides, and tripeptides, all of which are taken up by enterocytes of the mucosal wall. How preoteolytic enzymes are regulated ... 

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. 

Aminopeptidases are exopeptidases produced by intestinal cells that cleave one amino acid at a time from the iV-terminal end of peptides. 

Exopeptidases prodnced by intestinal epithelial cells act within the bmsh border and also within the cell. Aminopeptidases, located on the brush border, cleave one amino acid at a time from the amino end of peptides. Intracellular peptidases act on small peptides that are absorbed by the cells. 

The intestinal mucosa secretes an alkaline, watery juice containing several enzymes. This secretion mixes with pancreatic juice and bile to form the intestinal juice. The succus entericus, a pure intestinal secretion, is a thin liquid consisting of water, bicarbonate, and a few enzymes. Among the enzymes found in the intestinal secretion are exopeptidase, aminopeptidase, amylase, maltase, invertase, lactase, lipase, and entero-kinase, which activates trypsinogen. 

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. 

Exopeptidases Aminopeptidase Dipeptidase Intestinal mucosa Intestinal mucosa Terminal —NHs+ Dipeptides... 

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