Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.9 (enterokinase)
 675 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous administration of 1 U cholecystokinin-pancreozymin (CCK-PZ) to rats caused the release of enteropeptidase, alkaline phosphatase (AP), and sucrase to the intestinal lumen in the absence of a concomitant increase in luminal DNA. Thus, the hormone elicited hydrolase secretion was not due to cell desquamation. Pentagastrin also stimulated hydrolase release. Following CCK-PZ administration enteropeptidase was released preferentially over sucrase and AP and showed a linear correlation with total protein output. The specific enteropeptidase activity was higher in the perfusate following secretion than in the mocosa. Enteropeptidase was found mainly in soluble form in both mucosa and perfusate; addition of bile following enteropeptidase release further increased its activity. In contrast, sucrase and AP were found mainly in insoluble form in both mucosa and perfusate and their specific activities were higher in the mucosa. The presence of bile rendered both sucrase and AP more soluble in the perfusate. The data indicate that enteropeptidase is released by a specific secretory process and that its subcellular site of origin is different from that of sucrase and AP. By eliciting the coordinated release of trypsinogen, enteropeptidase and bile, CCK-PZ plays a central role in the initiation of protein digestion.
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PMID:Studies on intestinal enzyme secretion; the action of cholecystokinin-pancreozymin, pentagastrin and bile. 68 84

An endoproteolytic activity that specifically cleaves CCK 33, producing CCK 8, has been purified from a rat brain synaptosome preparation. The purification, which included anion exchange, chromatofocusing, hydroxyapatite, and gel filtration chromatography, resulted in a greater than 3000-fold increase in specific activity. This neutral endoprotease (pH optimum 8) exists as a 90-kDa species, which can be dissociated into active 40-kDa species. The enzyme is a non-trypsin serine protease, which is inhibited by diisopropyl-fluorophosphate and p-aminobenzamidine but not by soybean trypsin inhibitor, phenylmethylsulfonyl fluoride, aprotinin, or a number of thiol or metalloprotease inhibitors. It is highly substrate-specific and cleaves neither trypsin, enteropeptidase, kallikrein substrates, nor analogues of mono- or dibasic cleavage sites of prohormones other than pro-CCK. The endoprotease will not cleave CCK 12 desulfate or CCK (20-29), although these peptides contain common sequences with CCK-33. The protease does cleave [Glu27]CCK (20-29), a peptide in which the glutamate mimics the negative charge normally present on tyrosine sulfate. This suggests that the negative charge at position 27 is important in substrate recognition. The enzyme will also cleave CCK 33 and CCK (1-21) on the carboxyl-terminal side of a single lysine residue in position 11. The subcellular location and specificity of this endoprotease make it a good candidate for a CCK-processing protease.
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PMID:Characterization of a cholecystokinin 8-generating endoprotease purified from rat brain synaptosomes. 152 68

In a model of acute pancreatitis which requires that pancreatic enzymes leak from a permeable duct, we studied the role of intravenous enterokinase (195,000 daltons) in pancreatic enzyme activation. Anesthetized cats were given intravenous 16,16-dimethyl prostaglandin E2 to increase pancreatic blood flow and microvascular permeability. In some animals the permeability of the pancreatic duct was increased by perfusion of the duct with glycodeoxycholic acid (7.5 mM). Endogenous enzyme secretion was stimulated by IV CCK and secretin. Some cats also received enterokinase intravenously. Those animals that received PGE2, glycodeoxycholate, and enterokinase all developed pancreatitis. When any of these agents were not given the pancreases appeared normal. These findings were consistent with the hypothesis that intravenous enterokinase leaked from small pancreatic blood vessels into the pancreatic parenchyma and/or ducts where activation of pancreatic enzymes occurred. The development of pancreatitis appeared to require an increase in both microvascular and ductal permeability.
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PMID:Pancreatic duct and microvascular permeability to macromolecules. The relation to acute pancreatitis. 385 17

During the isolation of cholecystokinin from natural sources, as well as during its bioassay, inactivation by oxidation can cause problems. We have attempted to reactivate oxidized CCK by reduction at room temperature with N-methylmercaptoacetamide, recently stated to be the reducing agent of choice for the reduction of methionine sulfoxide to methionine [22]. We have not yet been unequivocally successful in these attempts, but the results seem promising. In the case of oxidized VIP and of oxidized tetragastrin, reduction with N-methylmercaptoacetamide does seem to result in reconversion of the peptides to their preoxidation states, as evidenced by thin layer chromatography on silica gel. We have, together with A. Holmgren and A. Ehrnberg, made observations suggesting the presence in rate liver cytosol of an enzyme which catalyzes the reductive reactivation of oxidized CCK with reduced thioredoxin as the immediate hydrogen donor. In collaboration with A. Light, Purdue University, we have found that enterokinase cleaves 39-CCK and 33-CCk with release of 8-CCK and the tetrapeptide immediately preceding it in the peptide chain. The conversion of 39-CCK to 33-CCK by the action of dipeptidyl amino-peptidase I has been confirmed.
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PMID:Additional observations on cholecystokinin and the vasoactive intestinal polypeptide. 628 92

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