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Gastrointestinal system
Published in Jagdish M. Gupta, John Beveridge, MCQs in Paediatrics, 2020
Jagdish M. Gupta, John Beveridge
Enteropeptidase converts trypsinogen to trypsin as well as procolipase to colipase, which activates lipase. Insufficiency causes malabsorption. Although starch contains many molecules of carbohydrate it has a low osmotic effect and therefore malabsorption due to amylase deficiency does not usually cause diarrhoea. Fat globules are found in the stools as fat remains insoluble in water (and is not absorbed) in the absence of bile salts. Ten percent of neuroblastomas secrete vasoactive intestinal peptide (VIP) which causes secretory diarrhoea. Peripheral neuritis in abetalipoproteinaemia is due to vitamin E malabsorption.
SBA Answers and Explanations
Published in Vivian A. Elwell, Jonathan M. Fishman, Rajat Chowdhury, SBAs for the MRCS Part A, 2018
Vivian A. Elwell, Jonathan M. Fishman, Rajat Chowdhury
The pancreatic enzymes degrade proteins, carbohydrates, lipids, and nucleic acids. The pancreatic proteolytic enzymes, trypsin and chymotrypsin, are secreted as inactive proenzymes that require activation in the small intestine. Enterokinase (enteropeptidase), an enzyme secreted by the duodenal mucosa, activates trypsinogen to form trypsin; trypsin then activates chymotrypsinogen to form chymotrypsin and other proenzymes into active enzymes. Trypsin can also activate trypsinogen; therefore once some trypsin is formed, there is an autocatalytic chain reaction. By releasing the enzymes as inactive zymogens that become activated far from their site of origin, this mechanism prevents autodigestion of the pancreas.
Liver, Gallbladder, and Exocrine Pancreas
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Russell C. Cattley, James A. Popp, Steven L. Vonderfecht
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).
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].
The discovery and development of transmembrane serine protease 2 (TMPRSS2) inhibitors as candidate drugs for the treatment of COVID-19
Published in Expert Opinion on Drug Discovery, 2022
Christiana Mantzourani, Sofia Vasilakaki, Velisaria-Eleni Gerogianni, George Kokotos
Trypsin-like serine proteases are proteolytic enzymes of the serine protease family that catalyze the cleavage of peptide bonds, showing specificity for basic amino acids. They have been found to be crucial in physiological processes, such as blood coagulation, immunity, and digestion. The study of serine proteases has led to the identification of a group of enzymes that are anchored to the membrane either by C-terminal (Type I) or N-terminal (Type II) transmembrane domains [18]. The TTSP or Type II subgroup of serine proteases consists of 17 members in humans. The hepsin/TMPRSS (transmembrane protease/serine) subfamily includes 7 members, namely, hepsin, TMPRSS2, TMPRSS3, TMPRSS4, TMPRSS5, MSPL (mosaic serine protease large-form), and enteropeptidase [19].
Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy
Published in Expert Opinion on Pharmacotherapy, 2023
Akiva Rosenzveig, Neil Garg, Shiavax J. Rao, Amreen K. Kanwal, Arjun Kanwal, Wilbert S. Aronow, Matthew W. Martinez
Neprilysin inhibitors are indicated in heart failure as well and function by inhibition of the enteropeptidase neprilysin. This enteropeptidase cleaves a multitude of peptides, such as bradykinin, substance P, angiotensin, and endothelin, achieving the desired results of mortality reduction in heart failure patients [75]. Angiotensin receptor neprilysin inhibitors (ARNI) in patients with HCM were analyzed the Sacubitril/Valsartan vs. Lifestyle in hypertrophic cardiomyopathy (SILICOFCM) trial. This ongoing randomized clinical trial enrolled 168 participants and aims to widely establish the possible advantages in functional clinical outcomes and quality of life of this drug class vs lifestyle interventional adjustments [75].