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)

To study the effects of trypsin on the pancreaticobiliary secretion and the release of secretin and cholecystokinin (CCK) to plasma, seven normal subjects were stimulated twice with duodenal perfusates containing 20 mM oleic acid (pH 6.0) with and without 1 g of bovine trypsin added per liter. In addition, six patients with advanced pancreatic insufficiency who received only the oleic acid were compared with eight normal subjects. The concentrations of secretin and CCK in plasma and the pancreatic enzyme and volume secretions were unaffected by the addition of trypsin, but the initial bile acid output and the bicarbonate secretion in the period after gallbladder emptying were reduced during perfusion with trypsin. The severely reduced enzyme secretion in chronic pancreatitis did not influence the basal or oleic acid-stimulated concentrations of the hormones in plasma. The study does not support the hypothesis of a trypsin-mediated negative feedback control of human pancreatic enzyme secretion. Furthermore, the reduced duodenal output of bicarbonate found in response to trypsin is not explained by changes in the release of secretin or CCK.
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PMID:Effect of trypsin on the hormonal regulation of the fat-stimulated human exocrine pancreas. 322 3

We investigated in-vitro the relation of the lipase and trypsin activity, containing in native duodenale juice, to pH-values, similar to them registered in the duodenum of patients with severe exocrine insufficiency. Therefore week alcaline duodenal juice was acidified by native gastric juice or hydrochloric acid to pH-value 7, 6, 5 und 4. The remaining activity was estimated after 5, 10, 15 and 20 minutes. We determined a fast inactivation of lipase at pH 5.0 or below (incubation of 5 minutes only decreased the activity to 35% of origin), and of trypsin at pH 4.0 or below (incubation of 5 minutes at this pH-value decreased the activity to 26% of origin). According to the denaturating effect on the enzymes, there was no difference between gastric juice and hypochloric acid. It is concluded, that the activity of decreased secreted pancreatic enzymes in severe exocrine pancreatic insufficiency and also of the oral substituted enzymes is additionally reduced by acidic duodenal circumstances, so that a gastric acid neutralizing or inhibiting therapy proves as necessary.
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PMID:[The pH dependence of lipase and trypsin activity]. 323 4

Concentrations of serum trypsin-like immunoreactivity (TLI) measured by radioimmunoassay were low (less than 1.9 micrograms/L) in 25 dogs with exocrine pancreatic insufficiency (EPI), compared with 100 clinically normal (control) dogs (5.2 to 34.0 micrograms/L; P less than 0.001; sensitivity, 100%). Serum TLI concentrations (5.5 to 35.0 micrograms/L) in a group of 50 dogs with small intestinal disease (SID) were not significantly different from those of control dogs, values being greater than the lower limit of the control range in all cases (specificity, 100%). Results of bentiromide (N-benzoyl-L-tyrosyl-p-aminobenzoic acid [BT-PABA]) tests and fecal proteolytic activity (determined by use of an azocasein substrate) were abnormal in 21 of 22 dogs with EPI (sensitivity, 95%). Bentiromide test results were subnormal in 13 of 35 dogs with SID (specificity, 63%), whereas fecal proteolytic activity was subnormal in 7 of 34 dogs with SID (specificity, 79%). It was concluded that assay of serum TLI is a highly sensitive and specific test for the identification of dogs with EPI.
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PMID:Sensitivity and specificity of radioimmunoassay of serum trypsin-like immunoreactivity for the diagnosis of canine exocrine pancreatic insufficiency. 325 6

Procedures have been validated for the investigation of the physical properties of canine microvillar membrane proteins by SDS-polyacrylamide gel electrophoresis. These have been used to examine mucosal samples from eight control dogs and from five dogs with naturally occurring exocrine pancreatic insufficiency (EPI) in order to evaluate the potential role of the pancreas in the normal turnover of microvillar membrane proteins in the dog. Gel scanning showed that the proportion of total membrane protein in bands corresponding to a molecular mass greater than 200 kDa was up to 20-times higher in dogs with EPI than in control dogs. In particular, a band of apparent molecular mass 218 kDa represented between 8 and 28% of membrane protein in all affected dogs, compared with only 0.5 to 1.8% in controls, and is most likely to contain single chains of both pro-maltase-glucoamylase and pro-sucrase-isomaltase. Incubation of microvillar membranes in vitro with either trypsin or canine pancreatic juice resulted in degradation of this high molecular mass band and a corresponding increase in the amount of protein in three bands representing molecular masses of 150, 133 and 106 kDa. In samples from control dogs aminopeptidase N was identified in the 133 kDa band by Western blotting and incubation with monospecific antiserum. These findings suggest that pancreatic enzymes play a major role in the normal post-translational processing of intestinal microvillar membrane proteins in the dog.
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PMID:Investigation of the physical properties of dog intestinal microvillar membrane proteins by polyacrylamide gel electrophoresis: a comparison between normal dogs and dogs with exocrine pancreatic insufficiency. 340 88

The effect on intraluminal postprandial concentrations of different pancreatic enzymes and on fat absorption were studied in 35 patients with advanced chronic pancreatitis with pancreatic insufficiency. Different regimes were studied: commercial Pankreatin (III) alone or in combination with Cimetidine, Pancrease, dispensed in microspheres, and commercial Pankreatin III compared to an equivalent uncoated preparation (Pankreatin I). Pankreatin induced significant increase in the intestinal concentration of amylase, lipase, and trypsin. Pretreatment with Cimetidine did not increase the enzyme concentrations further. The amount of enzymes in Pancrease capsules are rather small, no effect on concentrations of enzymes could be detected but treatment with Pancrease decreased significantly the fat excretion in faeces. The uncoated Pankreatin I induced a significantly higher increase in enzyme concentrations in the intestine compared to Pankreatin III but the overall effect tested on faecal fat excretion was identical with the two preparations. The results indicate that the estimation of concentration of enzyme at one level of the small intestine without and with enzyme substitution not necessarily gives information on the therapeutical effect of the enzymes.
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PMID:Exocrine pancreatic substitution: facts and controversies. 347 Sep 19

Plasma concentrations of cholecystokinin (CCK) have been reported to be elevated in patients with chronic pancreatitis. The elevations are suggested to be due to increased release of CCK from the upper small intestine secondary to the absence of protease activity (trypsin and chymotrypsin) in the intestinal lumen. We have studied plasma CCK levels before and after liquid as well as solid meals in eight patients with pancreatic insufficiency due to advanced chronic pancreatitis and in eight healthy controls. CCK concentrations were measured with a sensitive and specific radioimmunoassay using an antibody directed against the sulfated tyrosyl region of CCK. No differences in basal or maximal postprandial plasma CCK levels between patients and controls were observed. In the liquid meal study, basal CCK concentrations in patients and controls were 2.2 +/- 0.7 and 2.5 +/- 0.4 pM, respectively, with maximal postprandial concentrations of 9.6 +/- 2.2 and 11.2 +/- 1.4 pM. In the solid meal study, basal CCK concentrations in patients and controls were 2.5 +/- 0.6 and 2.6 +/- 0.4 pM, respectively, with maximal postprandial concentrations of 9.4 +/- 1.6 and 8.6 +/- 1.4 pM. The only difference observed was a significantly longer time interval to maximal plasma CCK levels in patients as compared with controls after the liquid meal. Two patients with no detectable trypsin activity in the small intestinal lumen during a Lundh test meal had basal CCK levels of 1.3 and 1.8 pM. Thus, the present study does not support the hypothesis that trypsin is involved in the regulation of CCK release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma cholecystokinin concentrations in patients with advanced chronic pancreatitis. 356 43

Using an inhibitor method, fasting levels of pancreatic isoamylase were measured in 46 healthy controls and in 218 patients undergoing a secretin-pancreozymin test for diagnostic purposes, and compared with immunoreactive trypsin (IRT). Exocrine pancreatic insufficiency was found in 82 of the patients. The specificity of both enzymes was high in patients with nonpancreatic diseases (pancreatic isoamylase: 98.5%, IRT: 96.3%). No patient with nonpancreatogenic steatorrhea had a low serum enzyme value. Sensitivity was, unfortunately, low in patients with exocrine pancreatic insufficiency (pancreatic isoamylase: 45.1%, IRT: 41.5%) and increased only slightly when patients after an acute attack of the disease, or patients with pseudocysts or older than 60 were excluded (pancreatic isoamylase: 67.9%, IRT: 58.5%). Although highly specific, pancreatic isoamylase measurement is not sensitive enough to be used as a screening test for exocrine pancreatic insufficiency but may be used to determine the etiology of steatorrhea.
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PMID:Estimation of serum pancreatic isoamylase: its role in the diagnosis of exocrine pancreatic insufficiency. 370 50

We evaluated the bentiromide test by analyzing para-aminobenzoic acid (PABA) in plasma and urine (a) for the identification of patients with complete pancreatic insufficiency and (b) as an alternative to the secretin-cholecystokinin test. Nine control subjects, 18 patients with cystic fibrosis, and 4 patients with Shwachman's syndrome were studied. Based upon the secretin-cholecystokinin test, pancreatic function was judged to be less than 0.1% of normal in 7 patients with cystic fibrosis and malabsorption and between 0.7% and 90% of control values in 11 patients with cystic fibrosis and 4 patients with Shwachman's syndrome without malabsorption. The bentiromide test was performed in two stages: first with bentiromide alone, then with equimolar free PABA. After ingestion of free PABA, the plasma profile and urinary excretion of PABA were comparable in controls, patients with cystic fibrosis, and patients with Shwachman's syndrome. Thirty minutes after oral bentiromide, plasma PABA values in patients with and without malabsorption were significantly lower than in the control group. From 60 to 180 min after ingestion, plasma PABA levels in patients without malabsorption were no different from controls; whereas levels in patients with malabsorption were significantly lower than in controls and in those without malabsorption, reaching the highest significance at 90 min. Similar results were obtained when the urinary excretion of PABA was considered. Only the 90-min plasma test reliably detected cystic fibrosis patients with steatorrhea, however. Duodenal colipase output was highly correlated with both the 90-min plasma test and the urinary excretion of PABA, with similar results for lipase and trypsin output. Reliable detection of pancreatic dysfunction, nevertheless, was not obtained even with the plasma test, in cystic fibrosis patients with greater than 5%-10% of the mean normal enzyme output. In patients with Shwachman's syndrome, none of whom had malabsorption, the plasma and urinary test failed to detect pancreatic dysfunction even with enzyme output as low as 1% of normal.
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PMID:Bentiromide test for assessing pancreatic dysfunction using analysis of para-aminobenzoic acid in plasma and urine. Studies in cystic fibrosis and Shwachman's syndrome. 387 4

Serum immunoreactive trypsin (IRT) and pancreatic lipase have been measured in 59 patients with cystic fibrosis (age 1 month-27 years). Follow-up values were obtained from 49 patients. Their serum enzyme levels were compared to those of 120 healthy children of all age groups. Faecal fat excretion was determined in selected patients (n = 23) to elucidate the relationship between serum enzyme levels and pancreatic exocrine function. In cystic fibrosis IRT and lipase showed a very similar age-correlated pattern: in infancy levels were markedly elevated. During the following years the concentrations of both enzymes decreased rapidly and were found to be far below the normal range after the 10th year of life. Elevated enzyme levels in infancy as well as low levels in all age groups coincided with steatorrhea. Older patients (11-27 years) without severe pancreatic insufficiency however, had IRT and lipase levels in or above the normal range. In healthy children there was no age dependency of IRT levels, whereas in the first 12 months of life lipase levels were significantly lower than in later childhood.
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PMID:Serum immunoreactive trypsin and pancreatic lipase in cystic fibrosis. 404 29

Hog pancreas was subfractionated and assessed for its ability to correct vitamin B(12) malabsorption in patients with pancreatic dysfunction and in rats with partial pancreatic extirpation. The constituent obtained from the pancreas that increased vitamin B(12) absorption in both humans and rats was soluble at 50,000 g, heat labile, acid stable, and approximately 20,000-25,0000 in molecular weight. The active subfractions contained tryptic and chymotryptic but no amylase or lipase activity. Thrice-crystallized trypsin corrected the vitamin B(12) malabsorption in both patients with pancreatic insufficiency and in rats with subtotal pancreatectomy. These data indicate that pancreatic proteolytic enzymes-in particular, trypsin-are necessary for optimal vitamin B(12) absorption.
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PMID:Trypsin-like nature of the pancreatic factor that corrects vitamin B12 malabsorption associated with pancreatic dysfunction. 471 58


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