Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two monoclonal antibodies (Mab) raised against human pancreatic trypsin 1, Mab G6 and A8, were previously isolated and characterized. The two Mab which recognize trypsinogen 1 are found to inhibit the activation of trypsinogen 1 by enterokinase. The inhibition of activation by the two Mab is concentration-dependent, rapid and virtually complete with Mab G6. Activation of trypsinogen 2 is totally inhibited by Mab G6, while Mab A8 has no effect on the activation of trypsinogen 2. The two monoclonal antibodies have opposite effects on the proteolytic activity of trypsin 1; Mab G6 increases proteolytic activity while Mab A8 inhibits trypsin activity by as much as 40%. This inhibition is concentration dependent but cannot account for the complete inhibition of activation of trypsinogen 1. Neither monoclonal antibody significantly inhibits the esterolytic activity of either form of human trypsin. Western-blot analysis of the reactivity of the two monoclonal antibodies with trypsinogens of various species shows that only Mab G6 cross-reacts with dog trypsinogen.
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PMID:Monoclonal antibodies to human pancreatic trypsin 1 inhibit the activation of human trypsinogens 1 and 2. 137 Dec 52

Proteinase species secreted by 10 human gastric carcinoma cell lines were analyzed by gelatin zymography and immunoblotting. These cell lines were classified into the following three groups with respect to proteinase secretion: cell lines secreting mainly gelatinases A and/or B; those secreting multiple types of serine proteinases; and those scarcely secreting these enzymes. Two cell lines of the second group, STKM-1 and MKN28, hardly secreted metalloproteinases but secreted the following four types of serine proteinases: (a) two trypsin-like enzymes (M(r) 26,000 and 24,000 in proenzyme forms); (b) a tissue kallikrein-like enzyme (M(r) 150,000 in a complex form); (c) a plasmin-like enzyme (M(r) 70,000); and (d) a plasminogen activator (urokinase-type, M(r) 57,000, from STKM-1 and tissue-type, M(r) 70,000, from MKN28). The M(r) 70,000 plasmin-like enzyme was also detected at lower levels in the conditioned media of four other cell lines (MKN1, MKN45, NUGC-3, and KATO III). The M(r) 24,000 proenzyme of the trypsin-like enzyme was purified from the serum-free conditioned medium of STKM-1. The proenzyme was activated by enterokinase treatment or autolytically by incubation at neutral pH, decreasing its apparent molecular weight from 24,000 to 23,000 on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The activated enzyme extensively degraded fibronectin, laminin, and gelatins and to lesser extents type I, III, IV, and V collagens at 30 degrees C. These results suggest that the matrix serine proteinases may play a major role in the matrix degradation by some kinds of human cancer cells.
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PMID:Multiple secretion of matrix serine proteinases by human gastric carcinoma cell lines. 138 87

An electrophoretic technique for the determination of enterokinase activity is described. The natural substrate trypsinogen is hydrolysed in the presence of soybean trypsin inhibitor. Under the conditions of assay, neither the trypsin inhibitor nor the trypsin-trypsin inhibitor complex are detected. Enterokinase activity can be determined in biological materials such as duodenal aspirates without any interference from trypsin activity. A significant correlation exists between the present technique and a spectrophotometric technique by which the liberation of trypsin activity is used to determine enterokinase activity.
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PMID:Determination of enterokinase activity by measuring the disappearance of trypsinogen. 139 26

Proteins with trypsin-like immunoreactivity (first detected by a specific immunoenzymatic assay) were isolated from CAPAN-1 and CFPAC-1 cell culture-conditioned media by chromatography on an immunoadsorbent prepared with a polyclonal antibody directed against trypsin 1. The adsorbed proteins were devoid of free trypsin activity but trypsin activity was present after enterokinase activation demonstrating that the immunoreactive trypsin present in cell supernatants corresponds to trypsinogens. When characterised by Western blotting using a monoclonal antibody directed against human trypsin 1 two protein bands corresponding to trypsinogen 1 (23 kDa) and trypsinogen 2 (25 kDa) gave a positive reaction. These results demonstrate the presence of trypsinogens 1 and 2 in CAPAN-1 and CFPAC-1 cells and in their culture-conditioned media.
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PMID:Characterization of trypsinogens 1 and 2 in two human pancreatic adenocarcinoma cell lines; CFPAC-1 and CAPAN-1. 175 57

Bovine enterokinase (enteropeptidase) is a serine protease and functions as the physiological activator of trypsinogen. The enzyme has a heavy chain (115 kD) covalently linked to a light or catalytic subunit (35 kD). The amino acid composition showed that the light chain has nine half-cystine residues (four as intramolecular disulfides) and that one half-cystine was in a disulfide link between the light and heavy subunits. The amino-terminal 27 residues of the S-vinylpyridyl derivative of the light chain were determined by gas-phase Edman degradation. The sequence has homologies with other serine proteases containing one or two chains. The homologies suggest that the catalytic subunit has the same three-dimensional structure and, therefore, the same mechanism of enzymatic action as pancreatic chymotrypsin, trypsin, and elastase. The presence of the conserved amino-terminal activation peptide sequence (IVGG) shows that enterokinase must have a zymogen precursor and that the two-chain enzyme arises from limited proteolysis during posttranslational processing.
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PMID:The amino-terminal sequence of the catalytic subunit of bovine enterokinase. 179 6

Pretreatment of the purified jack bean inhibitor with enterokinase activated human pancreatic preparation for 1 hr decreased its inhibitory capacity against crystalline bovine alpha-chymotrypsin by 30% but did not affect its trypsin inhibitory activity. Preincubation of the inhibitor with bovine chymotrypsin for 60 min resulted in partial loss of the inhibitory potency. Complex formation studies by gel chromatography on Sephadex G-100 indicated that the trypsin-inhibitor and chymotrypsin-inhibitor complexes dissociated to release inactivated inhibitor and active proteinases. Gel chromatography of the inhibitor in presence of 1.5 M ammonium sulphate indicated that the inhibitor showed a tendency to aggregate without loss of biological activity. However, in 4.2 M salt medium after 3 hr, antichymotryptic activity was lost completely without any effect on antitryptic activity. Treatment with methylamine, a nucleophile, caused a greater loss of antichymotryptic activity. Trinitrobenzene sulphonate and ethylacetamidate, the amino group modifiers, affected only the antichymotryptic activity. Treatment with ninhydrin, a specific arginine modifier, at pH 9.0 abolished the antitryptic activity whereas only 50% of the antichymotryptic activity was lost. Diethylpyrocarbonate, a histidine reagent, also decreased only the antitryptic activity. Modification of tryptophan and cysteine residues of the inhibitor had no effect on its inhibitory potency. Treatment with mercaptoethanol and sodium borohydride caused nearly 50% loss of antitryptic and antichymotryptic activities. Chloramine-T, a reagent that modifies methionine residues, inactivated the inhibitor.
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PMID:Chemical modification and complex formation studies with jack bean proteinase inhibitor. 181 77

It has been proposed that modulation of cholecystokinin (CCK) release by proteinases, proteinase inhibitors and protein is mediated by a pancreatic secretory trypsin inhibitor (PSTI), also called monitor peptide, in the rat. When human [125I]-PSTI was incubated with fasting small bowel juice or activated pancreatic juice greater than 88% of tracer eluted from gel chromatography in the characteristic position of hydrolysed PSTI. However, when the small bowel juice had been pre-incubated with soybean trypsin inhibitor 3 g/l, casein 5 g/l or lactalbumin 30 g/l, the hydrolysis of PSTI diminished so that 95%, 32%, and 33% respectively, now eluted in the characteristic position of free (i.e. intact and not bound to an enzyme) PSTI. When [125I]-PSTI was incubated with pure trypsin, chymotrypsin, elastase or enterokinase greater than 95% of tracer eluted in the position of PSTI-enzyme complex. Incubation of PSTI with trypsin plus one other enzyme was required to produce hydrolysis. The degree of protection of PSTI from hydrolysis in duodenal juice produced by these substances correlates with their affects on CCK release. Our findings support the hypothesis that PSTIs mediate the modulation of CCK release by intraluminal proteinases, proteinase inhibitors and proteins.
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PMID:Interactions of pancreatic secretory trypsin inhibitor in small intestinal juice: its hydrolysis and protection by intraluminal factors. 209 78

A global kinetic analysis of the mechanisms of the trypsinogen activation by enterokinase and trypsin is presented. The kinetic equations of both the transient-phase and the steady-state of these mechanisms are presented. In addition, we here derive the corresponding kinetic equations for the case in which the condition of rapid equilibrium prevails and we propose a kinetic data analysis. The significance of this approach to the treatment of other zymogen activation processes is discussed.
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PMID:Kinetics of the trypsinogen activation by enterokinase and trypsin. 221 4

Effects of FUT-175 on the pancreatic enzymes in vitro and in vivo in the enterokinase-induced experimental acute pancreatitis were investigated, and they were compared with those of gabexate and aprotinin. In in vitro experiments, FUT-175 inhibited the pancreatic protease activities 10 to 100 times more potently than gabexate. Furthermore, FUT-175 inhibited the enterokinase activity. Unlike aprotinin, FUT-175 inhibited alpha 2-macroglobulin bound trypsin activity as well as free trypsin. In in vivo experiments, at doses of 0.5-50 micrograms/kg/min, FUT-175 suppressed the elevated protease activities in the experimental acute pancreatitis more potently than gabexate. Differently from the action of aprotinin, FUT-175 suppressed trypsin activities both in the pancreas and in the plasma to the same extent. Furthermore, FUT-175 reduced the mortality of rats in the experimental acute pancreatitis in a dose-dependent manner. These data strongly support that FUT-175 is clinically useful in the therapy of acute pancreatitis.
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PMID:Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. 242 60

Serum immunoreactive trypsin (IRT) concentrations are elevated in newborn children with cystic fibrosis (CF) and subsequently fall, in most cases, to values below normal. To evaluate the molecular form(s) of IRT present in serum, we have performed serum activation by enterokinase and have measured serum IRT before and after activation. This approach is based on the postulate that enterokinase converts trypsinogen into trypsin, and this trypsin would then be mainly trapped by alpha 2-macroglobulin, thus escaping the assay. This assumption was confirmed in the 28 controls studied, where the mean percentage (+/- S.D.) of IRT recovery after serum activation was 13.7 +/- 2.9. Previous inhibition of alpha 2-macroglobulin by methylamine raised the recovery over 85%, confirming that most of the serum IRT present in controls was in the form of trypsinogen. Identical results were obtained in the serum of 10 obligate heterozygotes and in 57 out of 80 CF patients. In 23 CF patients the mean percentage of IRT recovery after serum activation was 41.6 +/- 17.6. Gel-filtration studies were performed on the sera of the CF patients showing an abnormal increase in the IRT recovery after serum activation. We could demonstrate that IRT was distributed in two fractions: one eluted with the Mr 25,000 protein as usually found in controls and other CF sera, and the other eluted with the Mr 75,000 protein corresponding to a complex of trypsin with alpha 1-proteinase inhibitor. These results show that, in these sera, active trypsin has been directly released in blood. These findings suggest that in some patients with CF, subclinical attacks of acute pancreatitis may occur.
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PMID:Behaviour of serum immunoreactive trypsin after serum activation by enterokinase in normal and cystic fibrosis patients. Evidence of a trypsin-alpha 1-proteinase inhibitor complex in some cystic fibrosis patients. 248 Aug 20


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