Last updated
Other names
  • H-Ala-Pro-Phe-Asp-Asp-Asp-Asp-Lys-OH
  • L-Alanyl-L-prolyl-L-phenylalanyl-L-alpha-aspartyl-L-alpha-aspartyl-L-alpha-aspartyl-L-alpha-aspartyl-L-lysine
3D model (JSmol)
MeSH D08.622.885
PubChem CID
  • C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N
Molar mass 921.915 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Trypsinogen ( /ˌtrɪpˈsɪnəən,-ˌɛn/ [1] [2] ) is the precursor form (or zymogen) of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by enteropeptidase, which is found in the intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine.



Trypsinogen is the proenzyme precursor of trypsin. Trypsinogen (the inactive form) is stored in the pancreas so that it may be released when required for protein digestion. The pancreas stores the inactive form trypsinogen because the active trypsin would cause severe damage to the tissue of the pancreas. Trypsinogen is released by the pancreas into the second part of the duodenum, via the pancreatic duct, along with other digestive enzymes. [3]

Activation of trypsinogen

Trypsinogen is activated by enteropeptidase (also known as enterokinase). Enteropeptidase is produced by the mucosa of duodenum and it cleaves the peptide bond of trypsinogen after residue 15, which is a lysine. The N-terminal peptide is discarded, and a slight rearrangement of the folded protein occurs. The newly formed N-terminal residue (residue 16) inserts into a cleft, where its α-amino group forms an ion pair with the aspartate near the active site serine, and results in the conformational rearrangement of other residues. The amino group of Gly 193 orientates itself into the correct position, which completes the oxyanion hole in active site, thereby activating the protein. [4] Since trypsin also cleaves the peptide bond after an arginine or a lysine, it can cleave other trypsinogen, and the activation process therefore becomes autocatalytic.

Safeguards against trypsinogen activation

Trypsin is produced, stored and released as the inactive trypsinogen to ensure that the protein is only activated in the appropriate location. Premature trypsin activation can be destructive and may trigger a series of events that lead to pancreatic self-digestion. In normal pancreas, around 5% of trypsinogens are thought to get activated[ citation needed ], therefore there are a number of defenses against such inappropriate activation. Trypsinogen is stored in intracellular vesicles in the pancreas called zymogen granules whose membranous walls are thought to be resistant to enzymatic degradation. A further safeguard against inappropriate trypsin activation is the presence of inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and serine protease inhibitor Kazal-type 1 (SPINK1), which binds to any trypsin formed. Trypsin autocatalytic activation of trypsinogen is also a slow process due to the presence of a large negative charge on the conserved N-terminal hexapeptide of trypsinogen, which repels the aspartate on the back of trypsin's specificity pocket. [5] Trypsin may also inactivate other trypsin by cleavage.

Serum trypsinogen

Serum trypsinogen is measured using a blood test. High levels are seen in acute pancreatitis and cystic fibrosis.[ citation needed ]

Trypsinogen isoforms

Three isoforms of trypsinogens may be found in human pancreatic juice. These are the cationic, anionic, and meso trypsinogen, and they account for 23.1%, 16%, and 0.5% of total pancreatic secretory proteins, respectively. [6] Other forms of trypsinogen have been found in other organisms.


The inappropriate activation of trypsinogen in the pancreas can lead to pancreatitis. Some type of pancreatitis may be associated with mutant forms of trypsinogen. A mutation at Arg 117, a trypsin-sensitive site, in cationic trypsinogen has been implicated in hereditary pancreatitis, a rare form of early-onset genetic disorder. Arg 117 may be a fail-safe mechanism by which trypsin, when activated within the pancreas, may become inactivated, and loss of this cleavage site would result in a loss of control and permit autodigestion resulting in pancreatitis. [7] Other mutations have also been found that are linked to pancreatitis. [8]

Related Research Articles

Chymotrypsin Digestive enzyme

Chymotrypsin (EC, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenum, where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side chain of the amino acid N-terminal to the scissile amide bond (the P1 position) is a large hydrophobic amino acid (tyrosine, tryptophan, and phenylalanine). These amino acids contain an aromatic ring in their side chain that fits into a hydrophobic pocket (the S1 position) of the enzyme. It is activated in the presence of trypsin. The hydrophobic and shape complementarity between the peptide substrate P1 side chain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing leucine and methionine at the P1 position.

Proteolysis Breakdown of proteins into smaller polypeptides or amino acids

Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, but may also occur by intra-molecular digestion.

Trypsin Family of digestive enzymes

Trypsin is a serine protease from the PA clan superfamily, found in the digestive system of many vertebrates, where it hydrolyzes proteins. Trypsin is formed in the small intestine when its proenzyme form, the trypsinogen produced by the pancreas, is activated. Trypsin cuts peptide chains mainly at the carboxyl side of the amino acids lysine or arginine. It is used for numerous biotechnological processes. The process is commonly referred to as trypsin proteolysis or trypsinization, and proteins that have been digested/treated with trypsin are said to have been trypsinized. Trypsin was discovered in 1876 by Wilhelm Kühne and was named from the Ancient Greek word for rubbing since it was first isolated by rubbing the pancreas with glycerin.

Pancreas Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins, and fats in food entering the duodenum from the stomach.

Protease Enzyme that cleaves other proteins into smaller peptides

A protease is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism, and cell signaling.


Chymotrypsinogen is an inactive precursor (zymogen) of chymotrypsin, a digestive enzyme which breaks proteins down into smaller peptides. Chymotrypsinogen is a single polypeptide chain consisting of 245 amino acid residues. It is synthesized in the acinar cells of the pancreas and stored inside membrane-bounded granules at the apex of the acinar cell. Release of the granules from the cell is stimulated by either a hormonal signal or a nerve impulse, and the granules spill into a duct leading into the duodenum.

A zymogen, also called a proenzyme, is an inactive precursor of an enzyme. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in Golgi bodies, where a specific part of the precursor enzyme is cleaved in order to activate it. The inactivating piece which is cleaved off can be a peptide unit, or can be independently folding domains comprising more than 100 residues. Although they limit the enzyme's ability, these N-terminal extensions of the enzyme or a “prosegment” often aid in the stabilization and folding of the enzyme they inhibit.

Serine protease Class of enzymes

Serine proteases are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serine proteases fall into two broad categories based on their structure: chymotrypsin-like (trypsin-like) or subtilisin-like.

Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption by the body. Digestive enzymes are found in the digestive tracts of animals and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining the stomach, in the pancreatic juice secreted by pancreatic exocrine cells, and in the secretions of cells lining the small and large intestines.

Enteropeptidase Class of enzymes

Enteropeptidase is an enzyme produced by cells of the duodenum and is involved in digestion in humans and other animals. Enteropeptidase converts trypsinogen into its active form trypsin, resulting in the subsequent activation of pancreatic digestive enzymes. Absence of enteropeptidase results in intestinal digestion impairment.

A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins. Trypsin is an enzyme involved in the breakdown of many different proteins, primarily as part of digestion in humans and other animals such as monogastrics and young ruminants. When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.


The drug aprotinin, is a small protein bovine pancreatic trypsin inhibitor (BPTI), or basic trypsin inhibitor of bovine pancreas, which is an antifibrinolytic molecule that inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use was to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; this was confirmed by follow-up studies. Trasylol sales were suspended in May 2008, except for very restricted research use. In February 2012 the European Medicines Agency (EMA) scientific committee reverted its previous standpoint regarding aprotinin, and has recommended that the suspension be lifted. Nordic became distributor of aprotinin in 2012.

Hereditary pancreatitis Medical condition

Hereditary pancreatitis (HP) is an inflammation of the pancreas due to genetic causes. It was first described in 1952 by Comfort and Steinberg but it was not until 1996 that Whitcomb et al isolated the first responsible mutation in the trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35).


A carboxypeptidase is a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide. This is in contrast to an aminopeptidases, which cleave peptide bonds at the N-terminus of proteins. Humans, animals, bacteria and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation.

Pancreatic elastase is a form of elastase that is produced in the acinar cells of the pancreas, initially produced as an inactive zymogen and later activated in the duodenum by trypsin. Elastases form a subfamily of serine proteases, characterized by a distinctive structure consisting of two beta barrel domains converging at the active site that hydrolyze amides and esters amongst many proteins in addition to elastin, a type of connective tissue that holds organs together. Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site. Although the recommended name is pancreatic elastase, it can also be referred to as elastase-1, pancreatopeptidase, PE, or serine elastase.

Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.

Trypsin 1

Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the PRSS1 gene. Trypsin-1 is the main isoform of trypsinogen secreted by pancreas, the others are trypsin-2, and trypsin-3 (meso-trypsinogen).


Pancreatic secretory trypsin inhibitor (PSTI) also known as serine protease inhibitor Kazal-type 1 (SPINK1) or tumor-associated trypsin inhibitor (TATI) is a protein that in humans is encoded by the SPINK1 gene.

PRSS2 Protein-coding gene in the species Homo sapiens

Protease, serine, 2 is a protein that in humans is encoded by the PRSS2 gene.

PRSS3 Protein-coding gene in the species Homo sapiens

Protease, serine, 3 is a protein that in humans is encoded by the PRSS3 gene.


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  2. "Trypsinogen". Unabridged (Online). n.d. Retrieved 2016-01-25.
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