|Trypsin-1 tetramer, human according to PDB 2RA3|
Existing structural: , ,
|Properties of human protein|
|Mass / length primary structure||224 amino acids|
|Isoforms||single-chain / double-chain|
|Gene names||; TRY1|
B06 AA07 D03 BA01 M09 AB52
|EC, category||serine protease,|
|Substrate||Arginine, lysine bonds in peptides|
Human trypsin is a mixture of three digestive enzymes that break down proteins in the small intestine and belong to the peptidases : trypsin-1 ( cationic trypsin, two thirds), trypsin-2 ( anionic trypsin, about one third) and trypsin-4 ( mesotrypsin , a few percent) ). Many similar enzymes in mammals, insects, fish and fungi also have the name trypsin.
Lack of trypsin-1 in humans leads to malnutrition due to protein deficiency . The cause can be a mutation in the TRY1 gene . Another consequence of such a mutation is hereditary pancreatitis , in which the body's own trypsin-1 cannot be broken down and the pancreas digests it. Mutation in the gene for trypsin-2 can contribute to chronic pancreatitis.
The proteases trypsin, chymotrypsin and carboxypeptidases are secreted from the pancreas as inactive zymogen precursors . The intestinal enzyme enteropeptidase , which is bound to the intestinal epithelium , controls the conversion of the precursor trypsinogen to trypsin. Trypsin activates itself ( positive feedback ) and converts chymotrypsinogen, proelastase as well as procarboxypeptidase and other inactive enzymes into their active forms (chymotrypsin, elastase and carboxypeptidase).
Trypsin is one of the endopeptidases that cleave proteins at certain points. Trypsin is a serine protease . Trypsin selectively splits peptide bonds according to the intestinal region according to the basic amino acids lysine , arginine and also according to modified cysteine . Proteinases are not specialized in certain proteins, but in certain amino acid sequences (structural features) within the proteins; this is important for the digestive process , as otherwise a specific enzyme would be required in the small intestine for each protein that occurs.
The pepsin released by the stomach wall has a similar function and effect .
Trypsin has a pH -Optimum 8 to 8.5. It is a widespread misconception that trypsin has an optimal pH level for the small intestine. However, the pH value in the small intestine is in the acidic to weakly alkaline range.
Enzyme in inflammatory processes
The effect of trypsin in the form of maggot therapy was noticed early on by Ambroise Paré , Dominique-Jean Larrey and William Stevenson Baer (1872–1931). Then an extract of the maggots was made, which, according to A. Läwn, had no effect.
In 1857 trypsin was discovered as such by Lucien Corvisart (1824–1882) and named in 1867 by Wilhelm Kühne . Since 1955 it has been used for inflammation of the oropharynx , nose and upper respiratory tract .
The proteolytic property of trypsin was observed in 1836 by Johannes Evangelista Purkinje and Seligmann Simon Pappenheim (1775–1840) and in 1856 by Claude Bernard . Lucien Corvisart began several experiments with the pancreatic secretions of dogs and sheep in 1857 in order to describe the effect more precisely.
In 1862 Alexander Jakulowitsch Danilewski was able to isolate the trypsin for the first time by rubbing it with sand and diatomaceous earth and then floating it in collodion . And in 1875 Rudolf Heidenhain (1834–1897) recognized that it was in the cells of the pancreas . It got its name from Wilhelm Kühne in 1876 .
In 1902 , Ernest Henry Starling and William Maddock Bayliss proved that the hormone secretin is responsible for the secretion of the pancreas. Emil Abderhalden (1877–1950), V. Hemtiquez and V Hemtiquez showed that trypsin and pepsin are two different enzymes Frankel in the years 1912–1916 each independently of one another.
In 1941, McClean and Hale found out that, among other things, trypsin has the ability to stop the progression of bacterial infection in a tissue by inactivating bacterial hyaluronidase . In combination with antibiotics, it was successfully used against local inflammation. There are records on this from Greuer and Hess from 1954.
In 1906 trypsin was used by John Beard in neoplasms and wrote down his results in the work "The Enzyme Treatment of Cancer" in 1911. At the same time, the intratumoral injection performed by Ferdinand Blumenthal , William Allan Pusey and PT Hald also resulted in the softening of tumors . British doctors had preparations manufactured industrially and treated other patients with them. Here, however, there was no effect, since the enzymes lose their activity when stored at room temperature , which was not yet known at the time, and this therapeutic approach was therefore discarded.
In cell culture laboratories , trypsin is used to detach adherent cells from the bottom of the culture dishes or to isolate cells. As long as the cells are not treated with trypsin for too long, they will not be damaged and only the extracellular proteins will be broken down.
In pharmaceutical terms , trypsin is now only used in combination preparations. Examples are Alphintern, Phlogenzym and Wobenzym N.
The activity of trypsin can be demonstrated by N -Benzoyl- D , L -arginine- p -nitroanilide (BAPNA). BAPNA is cleaved by the trypsin on the arginine, and p -nitroaniline is formed . The resulting increase in the concentration of p -nitroaniline can be followed spectroscopically at a wavelength of 405 nm .
- OMIM: Trypsin-1
- Tibor Sipos, Joseph R. Merkel: Effect of calcium ions on the activity, heat stability, and structure of trypsin . In: Biochemistry . tape 9 , no. 14 , 1970, pp. 2766-2775 , doi : 10.1021 / bi00816a003 .
- Laurence A. Moran: On the meaning of pH optima for enzyme activity. In: Sandwalk. December 9, 2014, accessed November 23, 2016 .
- J. Fallingborg: Intraluminal pH of the human gastrointestinal tract . In: Danish Medical Bulletin . tape 46 , no. 3 , 1999, ISSN 0907-8916 , p. 183-196 , PMID 10421978 .
- L. Ovesen, F. Bendtsen, U. Tage-Jensen, NT Pedersen, BR Gram, SJ Rune: Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency . In: Gastroenterology . tape 90 , no. 4 , 1986, pp. 958-962 , PMID 3949122 .
- Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2nd, revised and expanded edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2005, ISBN 978-3-8047-2113-5 , p. 110 .
- GTG bands (G-bands by trypsin using Giemsa). Institute for Human Genetics at Jena University Hospital , accessed on March 14, 2011.
- Jennifer McDowall / Interpro: Protein Of The Month: Trypsin and Chymotrypsin. (engl.)