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)

The intrinsic factor (IF)-cobalamin (Cbl) receptor activity in the mucosal homogenates progressively decreased after bile duct ligation in the rat, and 80% of the receptor activity was decreased in 96 h after ligation. The activity was restored to normal values of 5.5-6 pmol of IF-[57Co]Cbl bound/g mucosa when the assays were performed with both conjugated and unconjugated bile acids. When [57Co]Cbl bound to intrinsic factor was orally administered, the tissue levels of [57Co]Cbl were decreased by 75-80% in bile duct-ligated rats. The apical membrane receptor activity was also decreased after bile duct ligation; however, the activity was stimulated twofold by the addition of ileal cytosol and threefold with the addition of both ileal cytosol and taurocholate (1 mM). Enhanced binding of IF-[57Co]Cbl to the apical ileal brush-border membrane occurred with the use of dialyzed ileal cytosol but not with cytosol isolated from duodenal or proximal jejunal mucosa. The enhanced binding obtained with ileal cytosol was abolished after its treatment with trypsin. These results suggest that luminal bile acids optimize the binding of IF-Cbl by the ileal membrane receptor via interactions with a cytosolic factor and thus influence the gastrointestinal absorption of cobalamin.
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PMID:Intrinsic factor receptor activity and cobalamin transport in bile duct-ligated rats. 131 10

Factors influencing the effectivity of replacement therapy with Panpur and Creon were controlled by in vivo and in vitro investigations. Both enteric coated preparations were equally acid protected, they even seemed to be more effective in hyperacid than in anacid chronic pancreatitis patients. Thus the uneven results of Panpur treatment in pancreatic steatorrhea cannot be explained by acid inactivation of the enzymes. Creon dose-dependently ameliorated the steatorrhea as well as vitamin B12 absorption while crushed but not the intact Panpur has only some insignificant effect. Good mixing of pancreatin with the B12-intrinsic factor - R protein complex and with the protein containing meal seems to be important for digestion of protein as well as fat. Unbound, overflowing trypsin activity of Panpur resulted in fast proteolytic inactivation of lipase. This could be diminished by soybean trypsin inhibitor which increased the in vivo effectiveness of the preparate. In summary Creon fulfilled two important factors of replacement therapy more successfully than Panpur: good mixing with meals and stability of lipase against proteolytic splitting, that is why it proved to be more effective for replacement therapy of pancreatic insufficiency.
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PMID:[Requirements for successful pancreatic enzyme replacement therapy (comparative study of Kreon and Panpur)]. 230 64

Two groups of biological methods are commonly used to evaluate the exocrine pancreatic function: tests which require tubes for the collection of duodenal juice and the tubeless tests which are indirect tests of pancreatic function. In this study we have attempted to improve a new test: the test of haptocorrin degradation (THD). This test measures the transfer of labelled cobalamin from haptocorrin to the intrinsic factor which is provoked by the degradation of the haptocorrin by proteases in the duodenal juice. We present the results of this test in 90 patients with chronic pancreatitis. THD was first assayed with basal duodenal juice collected by naso duodenal tubing during secretin cerulein stimulation. In this study the sensitivity and specificity of THD was 0.86 and 0.93, respectively. In the second part of this study we demonstrated that the means of collecting duodenal juice had no effect on the results of THD. Duodenal juice was collected during a secretin cerulein test or during a routine upper gastrointestinal endoscopy after pancreatic stimulation with secretin. The sensitivity and specificity of THD was 0.90 and 0.94, respectively, when duodenal juice was collected during endoscopy. THD was significantly correlated with the NBT-PABA test, steatorrhea, and with the activity of trypsin and chymotrypsin in the duodenal juice. In this study, NBT-PABA was less sensitive than THD for the diagnosis of chronic pancreatitis (sensitivity was 0.70 and 0.89, respectively). The specificity of THD was estimated at 0.94. THD seemed to be a valuable adjunct to test pancreatic function. As upper gastrointestinal endoscopy is usually performed in patients with proved or suspected chronic pancreatitis, THD seems to have a place of choice among the other tests of pancreatic exocrine function. Further evaluation of this test by a multicentric prospective trial is now needed.
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PMID:[Evaluation of exocrine pancreatic function by the haptocorrin degradation test of the duodenal fluid collected by endoscopy]. 273 91

Human intrinsic factor was digested by trypsin and the resulting peptides purified by gelfiltration. Two peptides were sequenced to a total of 61 amino acid residues. Including the sequence for the N-terminal peptide and four cyanogen bromide peptides previously reported, we have now determined a total of 163 amino acid residues, that is a fraction of about 0.40 of the primary structure of human intrinsic factor. The 110 of the 163 residues known of human intrinsic factor are identical to the sequence of rat intrinsic factor.
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PMID:Human intrinsic factor. Its primary structure compared to the primary structure of rat intrinsic factor. 277 49

An in-vitro test of degradation of haptocorrin, a cobalamin-binding glycoprotein, was used to diagnose exocrine pancreatic dysfunction. This radioisotopic test (TDH) required only 50 microliters duodenal juice collected during endoscopy after stimulation with 1 U/kg secretin intravenously. The initial reaction mixture, composed of salivary haptocorrin saturated with cobalt-57-labelled cyanocobalamin and unsaturated intrinsic factor, was incubated with 25 microliters duodenal juice. The percentage of degraded haptocorrin was estimated from the proportion of labelled cyanocobalamin that was transferred from haptocorrin to intrinsic factor. The TDH result was 41.6 +/- 31.7% (SD) in a group of chronic pancreatitis patients (n = 22) and 91.5 +/- 4.8% in the control group (n = 47). The sensitivity and specificity for exocrine pancreatic dysfunction were estimated as 0.91 and 0.96, respectively, for a lower limit of normal values of 81.7%. A hyperbolic relation was found between the TDH and the trypsin or chymotrypsin activity in duodenal juice (p less than 0.001). In this study, the N-benzoyl-tyrosyl-p-aminobenzoic acid test was less sensitive than the TDH, since its result was abnormal in only 64% of the patients. The TDH was easier to carry out and less time-consuming than the determination of pancreatic enzyme output in duodenal juice collected after hormonal stimulation.
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PMID:In-vitro test of haptocorrin degradation for biological diagnosis of exocrine pancreatic dysfunction using duodenal juice collected during endoscopy. 287 85

It is now known that nonphysiological cobalamin analogs exist in the gastrointestinal tract, but their metabolic behavior is unclear. In this study, [57Co]cobinamide was used to study its affinity to hog intrinsic factor-cobalamin (IF-Cbl) receptor which has no species specificity against human IF-Cbl receptor, and its relation to human saliva R binder. Cobinamide was prepared from [57Co]cyanocobalamin and separated by paper chromatography. Human IF-Cbl complex was bound to IF-Cbl receptor but free cyanocobalamin was not. Although R binder-cobinamide was not bound to the IF-Cbl receptor, free cobinamide was bound to the IF-Cbl receptor to a significant extent (about one-half of IF-cyanocobalamin binding to the IF-Cbl receptor). We then investigated the binding of cobinamide to R binder and trypsin-treated R binder. Association constant of cobinamide binding to the IF-Cbl receptor was 1.0 X 10(9) M-1 which was much lower than that of cobinamide binding to trypsin-treated R binder and to untreated R binder. Further study indicated that cobinamide binding to the IF-Cbl receptor was blocked by the addition of R binder and also by trypsin-treated R binder. We conclude that one of the roles of R binder is to prevent binding of free cobalamin analogs to the IF-Cbl receptor in the gut.
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PMID:Binding of cobalamin analogs to intrinsic factor-cobalamin receptor and its prevention by R binder. 302 87

The effect of exoglycosidase, N-glycanase, trypsin and chymotrypsin was studied on the binding capacity and physicochemical properties of intrinsic factor and of haptocorrin using Superose 6 gel filtration. Intrinsic factor was purified as recently described by us. Haptocorrin was purified 6000-fold from human saliva using thermolabile affinity chromatography and high-performance cationic exchange chromatography with a specific activity of 20.6 nmol of cobalamin (Cbl) per mg protein and a yield of 44.7%. Exoglycosidases provoked a decrease of 54.3 and 78.2% of the Cbl binding capacity of haptocorrin and intrinsic factor, respectively. The sequential incubation of haptocorrin and intrinsic factor wit exoglycosidases and proteinases provoked a decrease of, respectively, 100 and 92.7% of their Cbl binding capacity, whereas the incubation with proteinase decreased the Cbl binding capacity of, respectively, 67.9 and 7.9%. The result of the incubation of [3H]intrinsic factor or [3H]haptocorrin with chymotrypsin and trypsin gave, respectively, no change in the elution position and a shift corresponding to a decrease of 50% of the estimated molecular mass. The estimated molecular mass of Cbl-intrinsic factor and of Cbl-haptocorrin decreased, respectively, to 57.1 kDa and to 88.1 kDa after incubation with exoglycosidases. It was concluded that (1) the carbohydrate core of intrinsic factor protects the whole protein whereas the carbohydrate core of haptocorrin protects only half part of the protein and (2) the carbohydrates are implicated in the formation of the cobalamin binding site of haptocorrin and intrinsic factor.
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PMID:Effect of glycosidases and proteinases on cobalamin binding and physicochemical properties of purified saturated haptocorrin and intrinsic factor. 305 9

Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl). Schilling tests were less than 1%, correcting to 5 to 15% after addition of hog intrinsic factor (IF). Gastric acid analysis and gastric biopsies were normal by light and electron microscopy. Gastric juice contained less than 3 pmol/ml of Cbl-binding ability due to IF (normal, 10-34 pmol/ml) and less than 2 pmol/ml of IF when measured with a radioimmunoassay (RIA) using normal human IF-[57Co]Cbl and rabbit anti-human IF serum (normal, 17-66 pmol/ml). However, RIA employing rabbit anti-hog IF serum gave values of 4-13 pmol/ml of IF (normal, 11-33 pmol/ml). This material had an apparent molecular weight of 40,000 (normal IF = 70,000). The IF from gastric biopsies appeared normal in terms of Cbl-binding ability, ileal binding, molecular weight, and both RIAs. This IF differed from normal mucosal IF, in that it lost its Cbl-binding ability when incubated at 37 degrees C at acid pH or in the presence of pepsin or trypsin. This loss was retarded when [57Co]Cbl was bound to the IF before these incubations. The stabilizing effects of neutralization and Cbl were also demonstrated in vivo. Schilling tests for the siblings of 0.4, 0.5, and 1.0% increased to 2.7, 5.7, and 4.3% (P less than 0.05), respectively, when the Schilling tests were repeated with the addition of NaHCO3 and cobinamide (which allows Cbl to bind immediately to IF). We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.
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PMID:Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis. 390 80

the absorption of vitamin B(12) in many animals requires its prior association with intrinsic factor (IF) and attachment to a specific receptor in the intestine. Employing Triton X-100, we have solubilized from guinea pig ileum a factor that binds intrinsic factor-vitamin B(12) complex (IF-B(12)). This binding factor was soluble to the extent that it was not sedimented by centrifugation at 100,000 g for 1 h and was small enough to enter the included volume of a Sepharose 4-B column. Furthermore, the ileal extract contained no microfine particles of membrane upon electron microscopic search. When a portion of the extract was incubated with a mixture of gastric juice and (57)Co-labeled vitamin B(12), a portion of the radioactivity was excluded from a Sephadex G-200 column. When gastric juice from a patient with a congenital abnormality of IF that prevented its binding to intestine was substituted for normal human gastric juice, radioactivity was not excluded from the gel, indicating failure of this abnormal IF-B(12) to bind to the intestinal extract. These data suggested the presence of a specific binder of IF-B(12) in the ileal mucosal extract. The reactions of normal IF-B(12) with the solubilized binding factor and with the membrane-bound "receptor" had several characteristics in common, including calcium dependence, temperature independence, and pH optimum near neutral. Extracts from the distal intestine showed more activity than did those from the proximal. The solubilized binding facter seemed specific for IF-B(12) in that it was not blocked by prior incubation with excesses of either free vitamin B(12) or IF. Binding activity of the extract was decreased by incubation at pH 2.0, by heating to 56 degrees C, and by incubation with chymotrypsin and dithiothretiol. Incubation with trypsin, neuraminidase, and sulphydryl blockers did not affect it. The Triton X-100 extract of guinea pig ileal mucosa contains a specific binding factor that probably is the receptor for IF-B(12). This appears to be a protein with function dependent on peptide and disulphide linkages.
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PMID:Solubilized receptor for intrinsic factor-Vitamin B12 complex from guinea pig intestinal mucosa. 485 16

Malignancies are common in the digestive tube, although with unequal distribution among segments. The aim of this paper was to compare available interpretations of the low cancer incidence in the small bowel and high in the large bowel. Supposed mechanisms include relatively small bacterial population, large secretion of liquid and rapid transit in the small bowel. Small bowel mucosa is the main absorptive part of the digestive tube with absorption rates for various nutrients so high that they can even be considered as clearances from the intestinal content. Consequently, these nutrients are not present in the large bowel. An alternative explanation is that an absorbable protective substance from the intraluminal content, might protect the mucosa from malignant transformations. It can be speculated that if there are any cytoprotective substances in the digested food their effect would be expressed mostly in the absorptive small intestine, leaving the large bowel mucosa unprotected. Vitamin B12 might be a possible candidate for this role. Cobalamin molecules are initially bound to haptocorrin (Hc) in the stomach, but in the small intestine B12 is transferred to intrinsic factor (IF) after the action of pancreatic trypsin on Hc. Cobalamin-IF complexes are absorbed in the terminal ileum leaving only a small fraction of B12 to enter the large bowel. We have tried to summarize available data regarding cancer incidences in digestive tube, segmental length and transit times of tube content. Cancer density is calculated as incidence per length and transit speed as length per transit time. Cancer incidences for seven intestinal segments were considered low if they were below one case per 100 000 inhabitants annually, while the low cancer density meant less than six cases per 100 000 inhabitants per metre. For instance, transverse colon was considered as a high cancer incidence place (2.15 cases), with low cancer density (4.3 cases/m). Transit speed more than 0.3 metre/hour was associated with low cancer incidences (accuracy 0.85) and low cancer density segments (accuracy 1.00). Cobalamin availability showed similar distribution, available in low incidence segments and unavailable in high incidence segments. Experimental studies are needed to quantify B12 availability in the large bowel and to determine whether small amounts of B12-IF or, perhaps, B12-haptocorrin complexes are absorbed by the small bowel mucosa. Without that, no cytoprotective effects of B12 in the digestive tube can be expected.
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PMID:Cancer incidences in the digestive tube: is cobalamin a small intestine cytoprotector? 1078 76


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