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. In the context of rat biology, it is also sometimes called monitor peptide.
Structure
Rat monitor peptide is composed of 61 amino acids (compared to 56 in humans) with a molecular weight of approximately 6500 daltons and is basic (PI = 9.0), acid stable, and heat resistant. It is only found in the zymogen granules of pancreatic acinar cells.
Function
SPINK functions as a competitive inhibitor of trypsin, which is a protease that can activate other proteases. It has been shown to prevent premature activation of pancreatic enzymes.
Monitor peptide binds to intestinal epithelial cells and induces CCK-release, which enhances pancreatic secretion in the presence of nutritional protein in the duodenum. When all nutritional protein is digested, monitor peptide is bound by trypsin and subsequently degraded, resulting in decreasing CCK-release and a reduction of pancreatic secretion.
Similar to CCK-releasing peptide (CCK-RP, homologous to DBI), it is trypsin sensitive and stimulates CCK release. It is possible that it also stimulates the growth of intestinal epithelial cells.
In rats
In addition to its role as a trypsin inhibitor, in rats it has also been found to stimulate the release of CCK from the enteroendocrine cells of the small intestine, and it has been called "monitor peptide" in this context. CCK then acts on the gallbladder to release bile and on the pancreas to release digestive enzymes, which help to further break down the food. This coordinated response helps to ensure efficient digestion and absorption of nutrients.
Clinical significance
Mutations in SPINK1 has been associated with hereditary pancreatitis and tropical pancreatitis. Trypsinogen is normally created and stored an inactive zymogen of trypsin in the pancreas, but occasionally will autoactivate itself. PSTI serves to cleave prematurely activated trypsin to prevent the enzyme from causing cellular damage to the organ. Without the function of PSTI, the pancreas is subject to repeated episodes of damage.
It has also been associated with prostate cancer.
History Monitor peptide was discovered in 1984 when it was purified from rat bile-pancreatic juice and the peptide sequence was elucidated.
See also Kazal-type serine protease inhibitor domain Pancreatitis
References
Further reading