Dipeptidase, intestinal

Dipeptidase Intestinal epithelium The bond joining two amino acids to form a dipeptide ... 

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

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 intestinal mucosal peptidases are distributed in the brush border and cytosol of the absorptive cell. There are, however, distinct differences between the brush border and cytosolic peptidases [75], The tetrapeptidase activity is associated exclusively with the brush border enzyme. Furthermore, brush border peptidases exhibit more activity against tripeptides than dipeptides, whereas the cytosolic enzymes show greater activity against dipeptides. Studies have demonstrated that more than 50% of dipeptidase activity was detected in the cytosol [76] and just 10% in the brush border membrane [77]. The brush border enzymes include... 

O Noren, H Sjostrom, L Josefsson. Studies on a soluble dipeptidase from pig intestinal mucosa. I. Purification and specificity. Biochem Biophys Acta 327 446-456, 1973. 

M Das, AN Radhakrishnan. Substrate specificity of a highly active dipeptidase purified from monkey small intestine. Biochem J 128 463-465, 1972. 

O Noren, E Dabelsteen, H Sjostrom, L Josefsson. Histological localization of two dipeptidases in the pig small intestine and liver, using immunofluorescence. Gastroenterology 72 87-92, 1977. 

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. 

Radhakrishnan, A. N. 1977. Intestinal dipeptidases and dipeptide transport in the monkey and in man. In Peptide Transport and Hydroly i iba Foundation Symposium, -359. New York Elsevier Science Publishers. 

Around 40% of the LMW fraction is absorbed from the small intestine in the rat (14). A part of the fraction may thus be present in the epithelial cells at the time of intracellular peptide hydrolysis. The effect of the LMW fraction on the activity of two cytosol enzymes, present in a preparation from hog intestine, is shown in Table III. Glycylleucine dipeptidase, which has a broad specificity (15), was inhibited at 0.7 mg/ml of the fraction, while proline cTTpeptidase, which catalyzes the hydrolysis of X-PRO (16), was not. 

Pepsin and the pancreatic proteases catalyze the conversion of dietary protein to peptides and amino acids. The aminopeptidases and the dipeptidases in the intestinal mucosa almost complete the hydrolysis of the peptides to amino acids, but some peptides, especially those containing glutamate, pass into the gut mucosal cells with the free amino acids. The aminopeptidases remove amino acids from the N-terminus of a peptide. 

Breakdown of ingested proteins occurs in the gastrointestinal tract by digestive enzymes pepsin from the stomach trypsin, chymotrypsin, and carboxypeptidase from the pancreas aminopeptidases and dipeptidases from the small intestinal wall. (Dipeptidases work on dipeptides. Aminopeptidase attacks the amino end of a peptide chain whereas carboxypeptidase attacks the carboxyl end of a peptide). Such digestion is certainly vital as 10 of the amino acids are essential, having to be acquired in the diet. 

One of the earliest suggestions that total enzymatic hydrolysis was possible came from the studies of Frankel (1916), who showed that over 90 % of the bonds in several proteins could be broken when proteolysis with pepsin, trypsin, and chymotrypsin was followed by prolonged hydrolysis with the erepsin preparation of Cohnheim (1901). The recognition in later years of several peptidases in intestinal exti acts which will specifically act upon bonds that are not susceptible to the endopoptidases (Bcrg-mann, 1942) probably accounts for these obseiwations. The specific peptidases such as prolidase, iminodipeptidase (prolinase), glycylglycine dipeptidase, tripeptidase, and leucine aminopeptidase, whi( h are present in mucosa, attack many of the bonds that resist the action of endopoptidases. 

Luminal and Membrane Metabolism of Peptides and Proteins. In meaningful studies on peptide and protein drug absorption in the small intestine, it is prerequisite to distinguish among cavital, membrane contact, and intracellular drug metabolism.Cavital metabolism takes place in the lumen of the small intestine by enzymes such as trypsin, chymotrypsin, carboxypepti-dase, and elastase, which are secreted by the pancreas. Membrane contact metabolism is carried out by aminopeptidases lo-calized on the brush border membrane. Intracellular metabolism occurs inside of the cells. The known intra-celluar enzymes are cytoplasmic peptidases, prolidase, dipeptidase, and tripeptidase.A more detailed dis-cussion of this topic is presented in section Intestinal Absorption Barriers, later. 

Aminopeptidases, dipeptidases, and tripeptidases are associated with the intestinal epithelial cells. 

Digestive enzymes produced by the intestinal epithelial cells (aminopep-tidases, dipeptidases, and tripeptidases) cleave the small peptides to amino acids. 

Erepsin an outdated term for the amino- and dipeptidases secreted by the mucous membranes of the small intestine. Thipeptidases are not included in the erepsin complex, but are present in the mucous membrane itself. 

Dipeptidases - Dipeptide hydrolases 3.4.13 Small intestine Dipeptides... 

Lindberg T. 1966. Intestinal dipeptidases Characterization, development and distribution of intestinal dipeptidases of the human foetus. Clin Sci 30 505-515. 

Glycyl-irLeudne Dipeptidase. Glycyl-L-leucine dipeptidase has been found in various mammalian tissues. It is named for the only sensitive simple peptide the only other known substrates are the N-methyl derivative, sarcosyl-L-leucine, and jS-alanyl-L-leucine which are split slowly. This activity is of interest because of the differences in metal activation shown by enzymes from different sources. Enzymes from rabbit muscle and hog intestinal mucosa were found to be activated by Mn++. Similar activities from human uterus and rat muscle were activated instead by Zn++. Both types of enzyme are inactivated by Ca++, which can be removed by phosphate buffers to leave active enzymes. ... 

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. 

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