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)

Enterokinase activates trypsinogen very rapidly and is itself resistant to proteolysis and endogenous inhibitors in blood and pancreas. Using a novel one-stage specific catalytic assay capable of detecting enterokinase in the presence of trypsin inhibitors, we have positively identified catalytically active enterokinase in human bile in each of 14 patients studied. Since the presence of active enterokinase in human bile was not explicable by duodeno-biliary reflux, enterokinase must have followed the pathway from gut to blood to liver to bile, previously identified in greater detail experimentally. We suggest that entry into the pancreatic duct system of bile-borne active enterokinase from the common bile duct may trigger necrotising acute pancreatitis.
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PMID:Catalytically active enterokinase in human bile. 638 63

Forty-two samples were taken from the contents of the proximal small intestine of two lactating dairy cows fitted with re-entrant duodenal cannula. Most samples were free of detectable amylase activity. The (chymo)trypsinogen present was only partially activated to (chymo)trypsin. The activation was continued in vitro: slowly at the original pH of the samples (between pH 2.8 and 4.2), and faster after neutralization or a slight alkalinization. The effect of Ca, EDTA and soybean inhibitor on the activation of trypsinogen was also studied. The pancreatic enzymes were inactive in the acid pH range of the samples, but pepsin was markedly active. At pH 3.8 casein was digested rapidly by purified pepsin and slowly by the samples (agar-plate experiments). In model experiments performed with purified enzymes, pepsin digested (chymo)trypsin rapidly at pH 1-2 and slowly at pH 3.8. In the intestinal juice (chymo)trypsin and their zymogens seemed to be unaffected by pepsin under the conditions of the samples. It is concluded that the conditions prevailing in the duodenum/upper jejunum of the experimental cows account for a gastric-type digestion, despite the presence of pancreatic enzymes. In vivo the intestinal contents pass in distal direction. Meanwhile the pH of the chyme gradually increases and gives rise to first an increase of enterokinase activity accounting for a faster activation of the zymogens; second a start of function of activated pancreatic proteases and third a gradual decrease of pepsin activity and finally to its irreversible denaturation. Thus the development of intestinal type digestion is delayed in ruminants.
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PMID:Investigations about influence of the content of plant crude protein in the ration on the utilization of urea in dairy cattle. 6. Digestive enzymes and their interactions in contents of proximal small intestine. 643 91

Mucosal enterokinase activity was established at intervals throughout the small intestine in guinea-pigs; maximum activity was present in the duodenum and proximal jejunum in new born as well as adult animals. Transposition of 5 cm lengths of small gut from the high enterokinase containing proximal region to the distal intestine and vice versa showed that mucosal enterokinase activity in the transposed segments was little changed after several weeks of healthy life. Isolation of proximal jejunal loops from luminal continuity resulted in the fall of mucosal enterokinase activity to minimal levels within 16 hours. Low levels of mucosal enterokinase activity were identified in loops of both proximal and distal jejunum 12 weeks after isolation. Luminal perfusion studies in vivo in proximal jejunal loops 24 hours after isolation showed that mucosal enterokinase activity could be restored to near normal levels within four to six hours by luminal sodium in the presence of active pancreatic endopeptidases, oligopeptides, L-amino acids, or D-glucose but not D-amino acids or D-fructose. Near normal mucosal enterokinase activity persisted in the loops for as long as luminal perfusion with 144 mM sodium and L-lysine or trypsin was maintained (24 hours). The time course of the restoration of mucosal enterokinase activity was compatible with an initial precursor activation as well as biosynthesis. The requirement for luminal sodium appeared to be absolute regardless of the co-substrate and supports the conclusion that mucosal enterokinase activity is dependent on mediated sodium transport. The ability of proximal intestinal enterocytes to respond to sodium flux with an increase in enterokinase activity is a property determined in intrauterine life: distal intestinal enterocytes may have functioning structural genes for enterokinase but appear to be unable to respond.
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PMID:Induction and maintenance of mucosal enterokinase activity in proximal small intestine by a genetically determined response to mediated sodium transport. 702 75

We report a novel assay method for enterokinase capable of detecting approx. 1 fmol of enzyme. The method depends on quantification of the release of specifically radiolabelled activation peptides from bovine trypsinogen and is unaffected by trypsin inhibitors. The assay is applicable to biological fluids such as serum. The substrate was produced by selective epsilon-amidination of bovine trypsinogen followed by acetylation with [3H]acetic anhydride and deprotection. The assay has been used to study the effects of pH, Ca2+, ionic strength abd glycodeoxycholate on enterokinase activity.
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PMID:Specific one-stage method for assay of enterokinase activity by release of radiolabelled activation peptides from alpha-N-[3H]acetyl-trypsinogen and the effect of calcium ions on the enzyme activity. 703 17

Duodenal fluids from control and cystic fibrosis (CF) patients were assayed for enterokinase (EK), trypsin and chymotrypsin activities. CF patients as a group were found to have higher basal EK activity in spite of low trypsin and chymotrypsin activities. In control patients, pancreozymin (CCK) injection led to increases in specific activities of trypsin and chymotrypsin and a decrease in EK but did not change the total EK activities. Secretin administration led to decreases in specific activities of trypsin and chymotrypsin compared to post-CCK levels. The total EK activities were greatly increased following secretin administration. Thus, secretin may have direct influence on the release of EK into the duodenum. CCK and secretin have no effect on the specific activities of trypsin, chymotrypsin and EK in CF patients. EK release in CF patients is either constitutive and therefore not affected by CCK and secretin or it has been fully induced by the low trypsin content and becomes unresponsive to further hormonal stimulation.
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PMID:Effect of pancreozymin and secretin on intraluminal enterokinase, trypsin, and chymotrypsin activities of cystic fibrosis and control children. 704 59

The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg). The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity. Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v. terbutaline, i.v. piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin. Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v. piperacillin or with a combination of FUT-175 plus i.v. terbutaline, plus i.v. piperacillin compared to controls.
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PMID:Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics. 747 69

Enterokinase is a serine protease of the duodenal brush border membrane that cleaves trypsinogen and produces active trypsin, thereby leading to the activation of many pancreatic digestive enzymes. Overlapping cDNA clones that encode the complete human enterokinase amino acid sequence were isolated from a human intestine cDNA library. Starting from the first ATG codon, the composite 3696 nt cDNA sequence contains an open reading frame of 3057 nt that encodes a 784 amino acid heavy chain followed by a 235 amino acid light chain; the two chains are linked by at least one disulfide bond. The heavy chain contains a potential N-terminal myristoylation site, a potential signal anchor sequence near the amino terminus, and six structural motifs that are found in otherwise unrelated proteins. These domains resemble motifs of the LDL receptor (two copies), complement component Clr (two copies), the metalloprotease meprin (one copy), and the macrophage scavenger receptor (one copy). The enterokinase light chain is homologous to the trypsin-like serine proteinases. These structural features are conserved among human, bovine, and porcine enterokinase. By Northern blotting, a 4.4 kb enterokinase mRNA was detected only in small intestine. The enterokinase gene was localized to human chromosome 21q21 by fluorescence in situ hybridization.
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PMID:cDNA sequence and chromosomal localization of human enterokinase, the proteolytic activator of trypsinogen. 771 57

Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be mediated by a potential signal-anchor sequence near the amino terminus. The amino terminus of bovine enterokinase also meets the known sequence requirements for protein N-myristoylation. The amino-terminal heavy chain contains domains that are homologous to segments of the low density lipoprotein receptor, complement components C1r and C1s, the macrophage scavenger receptor, and a recently described motif shared by the metalloprotease meprin and the Xenopus A5 neuronal recognition protein. The carboxyl-terminal light chain is homologous to the trypsin-like serine proteases. Thus, enterokinase is a mosaic protein with a complex evolutionary history. The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond. Therefore, enterokinase may not be the "first" enzyme of the intestinal digestive hydrolase cascade. The specificity of enterokinase for the DDDDK-I sequence of trypsinogen may be explained by complementary basic-amino acid residues clustered in potential S2-S5 subsites.
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PMID:Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains. 805 24

Enterokinase is a glycoprotein and is now designated enteropeptidase (E.C.3.4.4.8.). It is present in the duodenal and jejunal mucosa. Pancreatic proteolytic enzymes are secreted as proenzymes. Enterokinase converts trypsinogen to trypsin in the duodenal lumen. Duodenopancreatic reflux of duodenal enterokinase may be important in the pathogenesis of experimental and clinical acute pancreatitis. Congenital enterokinase deficiency is a distinct clinical entity characterized by diarrhea, failure to thrive, hypoproteinemia, and edema. Acquired enterokinase deficiency may occur in some diffuse small bowel diseases. Steatorrhea of celiac spruce may be due partly to the fact that deficiency of secretin and cholecystokinin may interfere with the action of enterokinase. The interrelationship between secretin, cholecystokinin, enterokinase, and bile salts is not completely understood.
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PMID:Enterokinase. 820 33

Phospholipase A2 (PLA2) has been postulated to play an important role in the pathogenesis of acute pancreatitis. To study the mechanism through which PLA2 may cause cellular damage, we used an in vitro model of isolated rat pancreatic acini prepared by collagenase digestion. Newly synthesized proteins were labeled by [35S]methionine. Cellular destruction was measured by the degree of release of radiolabeled proteins. Incubation of pancreatic acini with PLA2 alone caused only minor damage when very high concentrations of this enzyme were used. However, when acini were incubated with PLA2 in combination with its substrate, lecithin, cells were destroyed in a time- and concentration-dependent manner. Incubating cells with pancreatic homogenates and lecithin caused damage only when there had been prior activation of homogenates with either trypsin or enterokinase. The damage could be simulated by incubating acini with pure lysolecithin. Alcohol and cerulein did not further increase the destruction caused by PLA2 and lecithin. When acini were incubated with supernatants from another set of acini to which oleic acid had been added, a similar degree of damage resulted as compared with acini incubated with oleic acid alone. However, adding PLA2 to supernatants from acini preincubated with fatty acids significantly increased the degree of cellular necrosis. The destruction by PLA2 and lecithin was inhibited by albumin but could not be inhibited by gabexate mesilate, nafamostat mesilate, or cytidine diphosphocholine. We conclude that PLA2 could play a role in pancreatic acinar cell damage, especially in the spread of cellular necrosis within the organ, provided that its substrate, lecithin, is present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of phospholipase A2 in pancreatic acinar cell damage and possibilities of inhibition: studies with isolated rat pancreatic acini. 841 11


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