Trypsin is an enzyme, discovered in 1876 by the German physiologist Willhelm Kuhne, also the originator of the term enzyme. Put simply, trypsin catalyzes the degradation of other proteins, a function known as proteolysis. A member of a large class of metabolic enzymes secreted by the pancreas, trypsin serves as a way for living organisms to degrade proteins in a controllable manner. This function is carried out through trypsin’s catalysis of the hydrolytic reaction, a route of protien degradation by which the splitting of water molecules is used in the cleavage of the peptide bond. In particular, trypsin is highly selective for the positive side chains of the amino acids arginine and lysine. Peptide chains upon which trypsin acts are thus cleaved at the site of these amino acids to produce two smaller peptide chains.
Trypsin, itself being a protein, can also self-degrade in what is known as an autolytic reaction. In a degraded form, trypsin has no proteolytic function. This property of trypsin is vital for its regulation throughout the body, and also for the production of trypsin itself. Due to its degradative function, the body produces and stores trypsin in the form of the inactive protein tripsinogen. When tripsinogen is degraded by active trypsin, more trypsin is produced. The ability to activate and deactivate trypsin on demand allows the biological system it is active within to control its action with precision, both avoiding damage and sufficiently degrading the target proteins. Trypsin levels in feces serve as an important biomarker for pancreatic function in humans.
Composed of over 200 amino acid residues as a single chain polypeptide, trypsin is a large and globular protein with several important structures. Several forms result from the autolysis of trypsinogen, including the single-chain polypeptide beta-trypsin and the two-chained alpha-trypsin. Other forms of trypsin with increasing numbers of the basic chain are possible, but alpha and beta-trypsin are predominant.
A feature known as the catalytic triad is vital to trypsin’s function. The catalytic triad is composed of three amino acid residues, His57, Asp102 and Cys195, and together they compose the active site of trypsin by which it catalyzes the hydrolysis of proteins. There is also a Ca 2+ binding loop present in the protein’s structure, through which Ca 2+ ions can bind to trypsin and change its structure. In vivo, this has the effect of inhibiting Trypsin’s autolysation. Though many organisms produce inhibitors of trypsin in vivo, Ca 2+ binding inhibition is an important facet of trypsin’s regulation in living organims.
The integral biological role of trypsin is demonstrated by the deleterious effects produced by its deficiency. In the genetic disease known as Cystic Fibrosis, there is a disorder of the exocrine glands such as the pancreas. Enzymes responsible for various metabolic roles, including trypsin, are not secreted adequately by the pancreas in this disorder. As a result, poor growth, greasy stools and deficiencies in fat-soluble vitamins are produced. Trypsin also appears to play a role in the disease human hereditary pancreatis. In this disease, it appears to become activated while still stored in the pancreas, resulting in the digestion of pancreatic tissue and possibly death. These two examples, one of insufficient trypsin activity and another of excess activity, illustrate the vital and balanced role that trypsin plays in living organisms as well as the importance of understanding this role.
1. “PRSS1 protease, serine, 1 (trypsin 1)” Entrez Gene. December 2nd, 2008. National Center for Biotechnology Information. December 3rd, 2008. (Used to find the gene’s sequence and other resources.)
2. Worthington, Andrew. “Mutant Rat Trypsin” Department of Biology at Kenyon College.2003. Kenyon College. December 3rd, 2008. (Used for generalized information on the chemistry and biology of trypsin”
3. “UniProtKB/Swiss-Prot entry P07477” Uni-Prot/Swiss-ProtNovember 25, 2008. Universal Protien Resource. December 3rd, 2008. (Resource used for amino acid sequence.)
4. Haubrich, William. “Medical Meanings: A Glossary of Word Origins”American College of Physicians; 2nd edition (November 1, 2003). p. 24 (Resource used for citation of trypsin’s discoverer.)
5. R.Bollbach, M.Becker,H.W.Rotthauwe.”Serum immunoreactive trypsin and pancreatic lipase in cystic fibrosis” European Journal of Pediatrics. 144.2 July, 1985. 167-170. (Used for information about cystic fibrosis and trypsin.)
6. Kasserra, H.P Laidler, K.J. “pH effects on trypsin catalysis” Department of Chemistry, University of Ottawa. December 12, 1968. Canadian Journal of Chemistry. 47, 4021 (1969) (Used for data section)
7. Wang Y, Addess KJ, Chen J, Geer LY, He J, He S, Lu S, Madej T, Marchler-Bauer A, Thiessen PA, Zhang N, Bryant SH. “MMDB: annotating protein sequences with Entrez’s 3D-structure database.”, Nucleic Acids Res. 2007 Jan; 35(Database issue): D298-300. (Resource where molecular structure was obtained.)