Hereditary Pancreatitis
Dongyou Liu in Handbook of Tumor Syndromes, 2020
The PRSS1 gene on chromosome 7q34 spans 12.8 kb and encodes a 247 aa, 26.5 kDa cationic trypsinogen (or trypsinogen-1, an inactive form of trypsin), which is a member of the trypsin family of serine proteases. Secreted by the pancreas, trypsinogen is cleaved of an eight-amino-acid trypsinogen activation peptide (TAP) by enterokinase to form active trypsin in the small intestine. TAP may be also cleaved by trypsin in the presence of calcium and association with a binding site formed in the activation region. The resultant active (mature) trypsin is an endopeptidase that cleaves peptide chains following a lysine or arginine, and converts inactive zymogens produced by the pancreas into active digestive enzymes in the duodenum upon food exposure. A second calcium-binding site in trypsinogen as well as trypsin may be occupied by calcium, which prevents trypsin degradation by trypsin on the autolysis site (Arg-122), and by chymotrypsin C (CTRC) at Leu-81 within the calcium binding site [9].
Intestinal Absorption Of Macromolecules In The Adult *
Károly Baintner in Intestinal Absorption of Macromolecules and Immune Transmission from Mother to Young, 2019
The raw soybean meal does not contain toxins in the classical sense; however, if fed, its antinutritive factors suppress growth and animal production below the level predicted by its nutrient content. Protease inhibitors are the antinutritive factors of highest significance in the soybean, being responsible for approximately 40% of the total antinutritive effect if fed alone;837 the remaining 60% cannot be accounted for. Possible the different antinutritive factors act synergistically in sequence. The first step is the passage of the relatively resistant inhibitors through the stomach. Information about the passage of other antinutritive factors is lacking. The inhibitors suppress the activity of pancreatic proteases in the gut, especially the activity of trypsin. The lectin of the kidney bean (Phaseolus vulgaris) is able to bind to the glycocalyx and to damage the enterocytes;716, 717 a similar lectin (soyin) is found in the soybean and in most other legumes. Overgrowth of intestinal bacteria may add to the harmful effect. Urea passing from body fluids into the gut lumen across the leaky epithelium is split by bacterial and soybean ureases, releasing cytotoxic ammonia. In the last step highly antigenic storage proteins or antinutritive factors may be absorbed, e. g., urease or lipoxi-genase. The latter enzyme converts arachidonic acid to vasoactive prostanoids. The effect may be highest in insects who feed on 100% bean and have a primitive digestive system. Experimental proofs relating the absorption of antinutritive factors are lacking.
Liver, Gallbladder, and Exocrine Pancreas
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Secretion of pancreatic juice is the result of a complex interaction of neural, humoral, and paracrine mediators and the role played by each mediator varies from species to species (Pandiri 2014). In rodents, CCK secreted from the upper small intestine acts on the acinar cells of the pancreas via their CCKA receptor (CCKAR) to cause release of zymogen granules that are rich in pancreatic proenzymes. CCK also augments the action of secretin on pancreatic ducts to cause secretion of bicarbonate-rich fluid. Cholinergic stimulation also acts on acinar cells to cause the release of zymogen granules, and this effect appears to be mediated through vagal nerve stimulation. The enzymes of the pancreas are secreted as inactive proenzymes into the duodenum, where the intestinal brush border enzyme, enteropeptidase (enterokinase), converts trypsinogen to its active form. Trypsin can also activate trypsinogen; therefore, once trypsin is formed, there is an autocatalytic chain reaction. Trypsin subsequently converts other secreted pancreatic enzymes such as proelastase, procarboxypeptidases, and chymotrypsinogens to their active forms (Ganong 1991; Longnecker and Wilson 2002). Given the autocatalytic capacity of trypsin and its ability to activate other proenzymes in zymogen granules, it is not surprising that intra-acinar activation of trypsinogen to trypsin is signficant in the pathogenesis of acute pancreatitis (Dawra et al. 2011; Geldof et al. 1992).
A Method for Eliminating Fibroblast Contamination in Mouse and Human Primary Corneal Epithelial Cell Cultures
Published in Current Eye Research, 2023
Zhong Chen, Xiaowen Lu, Namratha Mylarapu, Sanjana Kuthyar, Om Sakhalkar, Mitchell A. Watsky
Fibroblast contamination of CEC cultures has been a problem for ophthalmic researchers for a long time. To solve this problem, in the present study, we examined several methods to find an optimal one. Trypsin is a serine digestive protease derived from porcine pancreas with the ability to cleave peptides on the c-terminal side of lysine and arginine amino acid residues. This feature allows it to efficiently induce cell dissociation by breaking down the proteins that facilitate cell adhesion.24 EDTA is a chelating agent with the ability to sequester metal ions such as calcium and magnesium. Trypsin-EDTA solution is a mixture of trypsin and EDTA, commonly used for dissociating cells from culture dish and tissue. Garcia-Posadas reported in a purification experiment of primary human conjunctival epithelial cell cultures, that after 5 min of contact with trypsin-EDTA, all the fibroblasts were detached, whereas most of the epithelial cells remained attached to the culture dish surface.8 In our present study, CEC treatment with trypsin-EDTA worked effectively for purification of both primary hCEC and mCEC cultures, along with purposefully mixed CEC and CSC cell cultures. We found that 210 s of trypsin-EDTA treatment was ideal for treating these cells, as observed by light microscopy and immunofluorescence staining.
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
The pancreas produces trypsinogen, an inactive precursor of trypsin. Trypsinogen is then secreted into the duodenum through the pancreatic duct. Once in the small intestine, the trypsinogen is activated by the enzyme enteropeptidase via proteolytic cleavage [54,55]. Trypsin is an endopeptidase and breaks peptide bonds down via a serine catalysis mechanism at an optimal pH of 7.5–8.5 [56]. The salmon calcitonin is a small peptide of 32 amino acids with a molecular weight of 3,432 Da and is a more potent analog of human calcitonin [57]. The salmon calcitonin was incubated with 0.5 μM trypsin in a sodium acetate (50 mM) buffer and it was completely degraded in 15 min [58]. The human granulocyte colony stimulating factor (G-CSF) is a major cytokine regulator of neutrophilic granulocytes and is able to stimulate the growth of neutrophil colonies from human bone marrow progenitor cells with a molecular weight of about 30,000 Da [59]. The incubation of 100 ug/ml of G-CSF with 1 ug/ml of trypsin revealed that G-CSF was susceptible to trypsin digestion and had about 30% intact protein at 4 h incubation [60].
Trypsinogen and chymotrypsinogen: potent anti-tumor agents
Published in Expert Opinion on Biological Therapy, 2021
Aitor González-Titos, Pablo Hernández-Camarero, Shivan Barungi, Juan Antonio Marchal, Julian Kenyon, Macarena Perán
The pancreas plays a very important role in the digestive function through the secretion of several enzymes necessary for the degradation of nutrients. These enzymes are secreted by acinar cells as zymogens (inactive forms also known as (pro)enzymes) [3]. Once secreted, they are transferred to the small intestine where they are activated. The most studied zymogens are Trypsinogen and Chymotrypsinogen. In the case of Trypsinogen, it is activated to Trypsin in the small intestine by enterokinase. Once activated, it is capable of activating the rest of the pancreatic zymogens, including Chymotrypsinogen into Chymotrypsin [4]. A failure in the production of these proteins can cause poor absorption of nutrients, the most common diseases that lead to exocrine pancreatic insufficiency are chronic pancreatitis and cystic fibrosis [5].
Related Knowledge Centers
- Digestive System
- Enzyme
- Hydrolysis
- Pancreas
- Protein
- Serine Protease
- Trypsinogen
- Zymogen
- Small Intestine
- Pa Clan of Proteases
- Digestive System