Topic
Trypsin 1
About: Trypsin 1 is a research topic. Over the lifetime, 28 publications have been published within this topic receiving 869 citations. The topic is also known as: TRP1 & TRY1.
Papers
TL;DR: Irrespective of the aetiology, mutations in the PRSS1 gene are not associated with chronic pancreatitis, including HP, and the N34S mutation in the SPINK1 gene shows a significant correlation in these patients.
Abstract: Background and aims: Mutations in the cationic trypsinogen (protease, serine, 1 (trypsin 1); PRSS1) gene are causally associated with recurrent acute and chronic pancreatitis. We investigated whether mutations in the PRSS1 gene are associated with hereditary and non-hereditary pancreatitis. As a modifier role has been proposed for trypsin inhibitor (serine protease inhibitor, Kazal type I; SPINK1) mutations, the role of SPINK1 mutations in these patients was also analysed.
Subjects and methods: The coding regions of PRSS1 and SPINK1 genes were sequenced in 290 controls and 198 patients, of whom 120 were diagnosed as idiopathic (ICP), 41 as alcoholic (ACP), and 37 as hereditary pancreatitis (HP). Twenty four unaffected relatives of HP probands were also analysed and genotype-phenotype correlations and statistical analyses were performed.
Results: No mutations in the PRSS1 gene were detected in any of the patients, including HP patients, while the N34S mutation was observed in the SPINK1 gene in the majority of HP patients (73%). Similarly, 26.8% of ACP (11 of 41) and 32.5% (39 of 120) of ICP patients also had SPINK1 mutations. The N34S mutation was observed in both homozygous and heterozygous conditions. In comparison, only 2.76% of the control population had the N34S allele (p<0.001). The P55S mutation was observed in one ICP and one ACP patient, and in three normal individuals. Genotype-phenotype correlations did not suggest any significant difference in the age of onset, severity of disease, or pancreatic endocrine insufficiency in patients with or without mutated SPINK1 and irrespective of the allelic status of N34S SPINK1.
Conclusions: Irrespective of the aetiology, mutations in the PRSS1 gene are not associated with chronic pancreatitis, including HP. In contrast, the N34S mutation in the SPINK1 gene shows a significant correlation in these patients. A comparable phenotype in terms of age of onset, diabetes mellitus, and other phenotypic features in patients with or without SPINK1 mutations and N34S homozygotes and heterozygotes suggests that there may still be involvement of other genetic or environmental factors.
121 citations
TL;DR: Four differently charged trypsins were purified from pyloric caeca of Atlantic salmon and for the first time a cationic isoform (isoelectric point above 9.3) has been isolated from a marine species.
Abstract: Four differently charged trypsins were purified from pyloric caeca of Atlantic salmon ( Salmo salar ). The isoelectric points of three anionic isoforms were 4.70, 4.60, and 4.55 (anionic trypsin I, II and III, respectively). And for the first time a cationic isoform (isoelectric point above 9.3) has been isolated from a marine species. The apparent molecular weights of all four isoforms were about 25 kDa as determined by SDS-PAGE. The salmon enzymes were inhibited by serine proteinase inhibitors in general and also by specific trypsin inhibitors. Anionic trypsin I and the cationic isoform were further examined. Anionic trypsin 1 showed the typical cold-adaptation features, low pH and temperature stability (also lower Gibb's free energy of GdnHCl-induced unfolding) and high catalytic efficiency as compared to the mammalian trypsins. The cationic isoform did not show these features, but resembled the mammalian trypsins.
103 citations
TL;DR: The most unexpected feature of the human trypsin 1 structure is in the phosphorylated state of tyrosine residue 151 in the present X-ray study, which strengthens the outstanding clustering of highly negative or highly positive electrostatic surface potentials.
79 citations
TL;DR: The two human anionic trypsinogens 1 and 2 were purified from human pancreatic juice by gel filtration on Sephadex G-100 and by chromatography on DEAE-cellulose and the reactions of the trypsins with chicken ovomucoid, Ascaris lumbricoides, human sperm and blood plasmatrypsin inhibitors were studied.
Abstract: The two human anionic trypsinogens 1 and 2 were purified from human pancreatic juice by gel filtration on Sephadex G-100 and by chromatography on DEAE-cellulose. After activation of their respective zymogens by porcine enterokinase, human trypsins 1 and 2 were studied for their reaction with a wide variety of proteinase inhibitors. Kunitz pancreatic trypsin inhibitor and human pancreatic secretory trypsin inhibitor completely inhibited both human trypsins at a stoichiometric inhibitor-to-enzyme ratio of one to one. In contrast, bovine pancreatic secretory trypsin inhibitor (Kazal's inhibitor) failed to inhibit either human trypsin. The inhibition of both human trypsins by porcine pancreatic secretory trypsin inhibitor was demonstrated. The reactions of the trypsins with chicken ovomucoid, Ascaris lumbricoides (type suis), human sperm and blood plasma trypsin inhibitors were studied. The most striking difference between the two human trypsins was the reaction with soybean trypsin inhibitor (Kunitz). Trypsin 2 was completely inhibited in a one-to-one molar ratio while trypsin 1 was poorly inhibited.
The presence of a prekallikrein in human pancreatic juice is dicussed.
78 citations
TL;DR: Findings have been confirmed in the European population, as reported by Aparisi et al in this issue of Gut, who describe a small series within a larger group of patients with non-alcoholic chronic pancreatitis, which is highly likely to include patients with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK1) which both increase the risk of chronic pancitis.
Abstract: Autoimmune pancreatitis is recognised worldwide as a T cell mediated, organ specific disease characterised by lymphocytic infiltration of the exocrine parenchyma with fibrosis and autoantibodies, including to carbonic anhydrase II. Increasing use of biopsy at endoscopic ultrasound may permit more frequent diagnosis without resection, but if doubt remains as to the presence of neoplasia, resection is preferable
During the five decades after Hashimoto described struma lymphomatosa of the thyroid gland featuring diffuse lymphocytic infiltration, fibrosis, and parenchymal atrophy,1 autoimmunity became increasingly recognised, such that when similar histological changes were described affecting the pancreas, an autoimmune mechanism was postulated.2 Autoimmune pancreatitis then remained among a number of plausible explanations for the appreciable minority of patients with chronic pancreatitis who give no history of alcohol abuse.3 More recently, Japanese workers again took up the baton, describing series of patients who had undergone pancreatic resection for suspected neoplasia but whose histology demonstrated lymphocytic infiltration of the exocrine parenchyma, with periductular and interlobular fibrosis.4,5 Further study demonstrated a T cell predominance to the infiltrate,5 autoantibodies directed against carbonic anhydrase II,6 an enzyme present in pancreatic as well as salivary ductal epithelium, and frequently high serum levels of IgG4.7 These findings have been confirmed in the European population, as reported by Aparisi et al in this issue of Gut ,8 who describe a small series within a larger group of patients with non-alcoholic chronic pancreatitis (see page 703) . Although not stated, such a group is highly likely to include patients with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)9 and serine protease inhibitor Kazal type 1 (SPINK1)10 which both increase the risk of chronic pancreatitis, as well as mutations of cationic trypsinogen (protease, serine, 1 (trypsin 1): PRSS1) which cause hereditary …
50 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2014 | 1 |
| 2011 | 1 |
| 2009 | 1 |
| 2008 | 1 |
| 2006 | 1 |
| 2005 | 1 |