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)

The activation of canine anionic and cationic trypsinogen by enterokinase, trypsin, thrombin, plasmin and extracts from canine granulocytes were studied in vitro. Enterokinase activates both trypsinogens about 1000 times faster than trypsin. The enterokinase-catalyzed activation is not inhibited by the main serum protease inhibitors, alpha-macroglobulin and alpha 1-antitrypsin. alpha-Macroglobulin cannot inhibit the activation of the trypsinogens by trypsin but this reaction is completely inhibited by alpha 1-antitrypsin. The results are discussed in relation to the pathogenesis of acute pancreatitis.
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PMID:Studies on the activation of canine trypsinogens in vitro. 9 42

A specific radioimmunoassay has been developed for human pancreatic cationic trypsin. The assay has been employed for the determination of immunoreactive forms of pancreatic cationic trypsin in blood. The trypsin employed as radioiodinated tracer in the assay was inactivated with tosyl-L-lysine chloromethyl ketone (TLCK) to prevent binding of the tracer to the serum inhibitors while maintaining its immunoreactivity. The average normal serum level determined was 26 ng/ml, with a range of 12--41 ng/ml. Eight of nine patients with acute pancreatic inflammation had at least a 15-fold elevation of total serum immunoreactive cationic trypsin. Cationic trypsinogen and cationic trypsin bound to alpha1-antitrypsin cross-react strongly in the radioimmunoassay. Thus it is possible to measure these potential molecular forms of cationic trypsin in serum. When normal human serum was fractionated on Sephadex G-200, all of the immunoreactive material eluted as a single peak of approximately 23,000 mol wt. No cationic trypsin could be detected in association with alpha1-antitrypsin or alpha2-macroglobulin. The 23,000-mol-wt peak was definitively shown to contain trypsinogen by affinity chromatography and by activation with human enteropeptidase. The identification of cationic trypsinogen in blood implies that the zymogen is secreted into the circulation by the pancreas rather than entering the bloodstream via absorption from the intestine.
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PMID:Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay. 43 51

The activation of human trypsinogens 1 and 2 by porcine enterokinase at pH 5.6 shows that the two human zymogens are equivalent substrates for this enzyme and that both proteins are activated faster than the cationic bovine trypsinogen. At pH 8.0 and in the presence of 20 mM calcium the two human trypsinogens are activated by either human trypsin at the same rate but the affinity of both trypsins is higher for trypsinogen 1 than for trypsinogen 2. Two Ca2+ binding sites are identified in the two human zymogens and their pK(Ca2+) values determined. For trypsinogen 1 the values are respectively of 2.8 and 3.3 for the primary and secondary Ca2+ binding sites, and for trypsinogen 2 of 3.4 and 2.7. These values are markedly different from those obtained for bovine cationic trypsinogen, especially in the case of trypsinogen 1. These results point out a different degree of saturation of the calcium binding sites of the 2 human zymogens that must exist in physiological conditions, suggesting different biological activities of the two trypsinogens.
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PMID:Comparative studies on the mechanism of activation of the two human trypsinogens. 50 71

Human pancreatic cationic trypsinogen has been purified to homogenity from an acetone powder of pancreatic tissue. After an initial ion exchange chromatography step on sulfopropyl (SP)-Sephadex at pH 2.6, cationic trypsinogen was separated from the majority of trypsin activity by passage through an affinity column of lima bean trypsin inhibitor-agarose at high ionic strength. The zymogen was then further purified by affinity chromatography on the same material at low ionic strength. Highly purified trypsinogen was resolved from containing chymotrypsinogen by ion exchange chromatography on SP-Sephadex at pH 6.0. The purified zymogen was shown to be homogeneous by polyacrylamide gel electrophoresis at pH 2.1 and at pH 4.3 as well as by discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The autoactivation of human trypsinogen was investigated at pH 5.6 and at pH 8.0. The rate of autoactivation of the human zymogen is rapid at pH 5.6 and is maximal in approximately 1 mM Ca2+. These results are in marked contrast to those previously reported for autoactivation of bovine trypsinogen, which is extremely slow at pH 5.6 and which shows a dependence on at least 50 mM Ca2+ for maximum rate of activation (MacDonald, M. R., AND Kunitz, M. (1941) J. Gen. Physiol. 25, 53-73).
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PMID:Human cationic trypsinogen. Purification, characterization, and characteristics of autoactivation. 63 97

A cDNA clone encoding an anionic form of bovine trypsinogen was isolated from a pancreatic cDNA library. The corresponding 855-nucleotide mRNA contains a short 5' noncoding region of 8 nucleotides and a long 3' noncoding region of 56 nucleotides in addition to a poly(A) tail of at least 50 nucleotides. The deduced amino acid sequence for the anionic pretrypsinogen (247 residues) includes the N-terminal 15-amino-acid signal peptide followed by an 8-amino-acid activation peptide. The zymogen (232 residues) contains an additional C-terminal serine, compared with the amino acid sequence of bovine cationic trypsinogen. The identity between the anionic and cationic forms of bovine trypsinogen (65%) is lower than that existing between the anionic protein and other mammalian anionic trypsinogens (73-85%), suggesting that trypsin gene duplication in mammals occurred prior to the evolutionary events responsible for the species divergence. Bovine pancreatic anionic trypsin possesses all the key amino acids characteristic of the serine protease family.
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PMID:Isolation and nucleotide sequence of cDNA clone for bovine pancreatic anionic trypsinogen. Structural identity within the trypsin family. 170 Nov 47

Urine cytology and blood lymphocyte blastogenesis were evaluated as indicators of allograft rejection in a porcine pancreatic transplantation model. The percentage of activated lymphocytes and/or blasts was significantly increased during the rejection phase. Positive cytology was present in all rejection episodes. An increased thymidine uptake of blood lymphocytes and a decreased uridine/thymidine uptake quotient were seen prior to the onset of rejection. The reported dissociation of anionic and cationic trypsin levels in serum and urine after transplantation was not seen after simple urinary diversion of the pancreatic juice. This supports the hypothesis that a decreased synthesis of cationic trypsinogen compared with anionic trypsinogen occurs after porcine pancreatic transplantation.
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PMID:Early indicators of allograft rejection in a porcine pancreatic transplantation model. 187 58

Circulating concentrations of digestive enzymes, certain lysosomal hydrolases and protease inhibitors were measured in 19 heavy smokers and 13 non-smokers before (basal) and at 15, 30, and 60 minutes after a single intravenous injection of secretin (75 CU). In smokers, basal serum amylase and immunoreactive pancreatic elastase 2 (IRE2) concentrations were about 100% and 25% higher respectively, than in the non-smokers, whereas, no differences were observed in basal immunoreactive cationic trypsinogen (IRCT) concentrations and in acid phosphatase and beta-glucuronidase activities between the two groups. Furthermore, a single injection of secretin to cigarette smokers significantly increased serum amylase, IRCT and IRE2 by 155%, 200%, and 100%, respectively when compared with their corresponding basal levels. No such increment was observed in the non-smokers. In addition, there were no significant differences in serum trypsin or elastase inhibitory capacity or immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin levels between smokers and non-smokers. The levels and inhibitory capacity of these protease inhibitors was also not affected by secretin injection. These data suggest that cigarette smoking enhances the responsiveness of the exocrine pancreas to a physiological stimulus such as secretin, with resultant substantial increase in the concentrations of pancreatic hydrolases in blood.
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PMID:Raised serum concentrations of pancreatic enzymes in cigarette smokers. 243 81

A simple method for the purification of anionic and cationic trypsinogen and trypsin from human pancreatic juice applying affinity chromatography on aprotinin coupled Sepharose is described together with the N-terminal amino acid sequences for both trypsinogens. In addition, enzyme-linked immunoabsorbent assay (ELISA) methods for the determination of anionic and cationic trypsin-like immunoreactivity (irAT and irCT) are described. Normal serum levels are 21.3 +/- 7.4 micrograms/l and 27.8 +/- 9.0 microgram/l for irAT and irCT respectively and the accuracy of these assays is 6-10%. In our population, the normal ratio between irCT and irAT in serum is 1.36 +/- 0.42. In normal serum trypsin-like immunoreactivity consists solely of trypsinogen. In acute pancreatitis there is an increase over normal of both irAT and irCT with a proportionally greater increase in irAT than irCT. Similar changes are also found in uremic patients.
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PMID:Immunoreactive anionic and cationic trypsin in human serum. 259 66

Incubation at 37 degrees C of human cationic trypsinogen purified by PAGE electrophoresis, results in development of proteolytic activity (enzyme Y) capable of rapidly degrading cationic and anionic trypsinogens to inert products. Enzyme Y appears to be a serine protease with a molecular weight of about 20,000 daltons and is different from any of the known pancreatic enzymes. The active enzyme may be derived from trypsinogen itself or a hitherto unrecognized precursor contaminating the trypsinogen fraction used in this work. Appearance of enzyme Y activity seems to be associated with the presence of traces of free trypsin. Enzyme Y possesses insignificant or no activity when tested with a variety of synthetic trypsin, chymotrypsin and other protease substrates. It is not inactivated by the specific trypsin and chymotrypsin inhibitors TLCK and TPCK, but its activity is reduced gradually by increasing concentrations of pancreatic secretory trypsin inhibitor. Ca2+ concentrations greater than 3 mM strongly inhibit enzyme Y, and diisopropylfluorophosphate completely inactivates it. The enzyme is stable when incubated at pH 1.9 and 37 degrees C for 30 min and its activity is not abolished by treatment with Hg2+. When added to pancreatic juice with low inhibitor content it causes rapid inactivation of zymogens without significant release of active enzymes or reduction of pancreatic trypsin inhibitor. Its physiological role may be perceived as a second line of defense against premature intrapancreatic activation of zymogens. Enzyme Y activity may be generated when trypsin inhibitor, the first line of defense, is sufficiently depleted by complex formation with inappropriately released trypsin to permit dissociation of a small amount of trypsin from this complex. This in turn may lead to activation of enzyme Y and inactivation of the zymogens of pancreatic proteases.
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PMID:A possible zymogen self-destruct mechanism preventing pancreatic autodigestion. 316 6

We evaluated the behavior of serum cationic trypsinogen (SCT), an enzyme of solely pancreatic origin, in 30 patients with chronic pancreatitis and 25 healthy subjects as a control, after secretin and bombesin stimulation. After both the stimulations, serum cationic trypsinogen is unable to distinguish between the healthy control subjects and the patients with chronic pancreatitis. On the other hand, after secretin, the enzyme is able to separate chronic pancreatitis patients with different levels of exocrine function insufficiency. It does so with a greater statistical significance than that obtained by the rapid injection of bombesin and equal to that of trypsin into the duodenal juice during duodenal intubation. For these reasons, as well as the absence of any side-effects, secretin is preferred to bombesin stimulation in the evaluation of the exocrine pancreatic function in patients with chronic pancreatitis.
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PMID:Different responses of serum cationic trypsinogen to secretin and bombesin in normal subjects and patients with chronic alcoholic pancreatitis. 343 9


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