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:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase is a proteinase that normally functions as a plasminogen activator. It is detected in a number of tissues and can be expressed by inflammatory cells such as macrophages and polymorphonuclear leucocytes. Addition of human urokinase to cultures of mucoid or nonmucoid variants of Pseudomonas aeruginosa (strain PAO and clinical isolates from patients with cystic fibrosis) or Pseudomonas cepacia incubated in a minimal medium under nonshaking (oxygen limited) conditions led to dose-dependent enhancement of bacterial growth. The enzyme exhibited a minimal effect on the growth of bacteria when cultured under more intense aeration conditions. This enhancement of bacterial growth by urokinase required the presence of active enzyme and was not detected with inactivated enzyme or noncatalytic domains of the enzyme. Enhancement of bacterial growth was not observed following incubation of P. aeruginosa with other proteinases including thrombin, neutrophil elastase, trypsin, chymotrypsin, or pseudomonas elastase and pseudomonas alkaline proteinase. Therefore, the observed effect of urokinase was relatively specific for this enzyme. As urokinase is a natural constituent of the lung, this enzyme could contribute to bacterial growth during pulmonary infections, particularly in an inflammatory environment in which the oxygen tension may be reduced.
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PMID:Urokinase enhances the growth of Pseudomonas spp. in vitro under nonshaking (oxygen limited) conditions. 803 52

Pancreatic transplantation for endocrine replacement is well-established for insulin-dependent diabetes mellitus. Exocrine pancreatic function after pancreas transplantation has been maintained after orthotopic cluster transplants for malignancy, and restoration of adequate exocrine function in a previously deficient patient has been reported in a patient with chronic pancreatitis who developed labile diabetes and steatorrhea after pancreatectomy. We performed a triple organ transplant (pancreas, liver and kidney) in a patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to cystic fibrosis (CF) after he developed hepatic and renal failure. Pancreatic exocrine secretions were drained enterically to the jejunum. At 24-month follow-up, malabsorption is absent. The 3-day stool fat, stool trypsin and chymotrypsin are normal. Serum carotene is within the normal range. Exocrine pancreatic insufficiency in CF patients can be corrected by pancreas transplantation. However, routine use in CF is precluded by the risks of surgery and immunosuppression. For diabetic patients with pancreatic exocrine insufficiency who require another organ transplant (e.g., lung, liver, or kidney), simultaneous pancreas transplantation with the exocrine secretions directed into the upper gastrointestinal tract should be considered.
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PMID:Restoration of exocrine pancreatic function following pancreas-liver-kidney transplantation in a cystic fibrosis patient. 813 59

Chronic pancreatitis (adults) and cystic fibrosis (children) are the most common diseases leading to exocrine pancreatic insufficiency that, when reduced to < 5% of normal function, is characterised by steatorrhoea. The pathogenesis of the former condition is outlined, and recent concepts are emphasized. Biochemical tests to detect pancreatic insufficiency and to identify pancreatic disease as the cause of steatorrhoea include: serum enzyme tests (lipase, amylase, trypsin); stool chymotrypsin; isotopic tests based upon the assimilation of [14C] lipids and starch or excretion of the isotope as breath CO2, as well as the dual-labelled Schilling test; oral function tests utilising substrates hydrolysed by pancreatic enzymes such as benzoyl tyrosyl-p-aminobenzoic acid and fluorescein dilaurate; and duodenal intubation studies following meal-induced or hormonal stimulation of the pancreas. The rationale for these tests and the cumulative clinical experience of their utility are reviewed. A recommended diagnostic strategy is briefly presented. The role of various biochemical procedures to evaluate the efficacy of pancreatic enzyme replacement therapy is also described.
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PMID:Biochemical tests in the diagnosis of chronic pancreatitis and in the evaluation of pancreatic insufficiency. 824 88

The kinetic investigation of the inhibition of human pancreatic trypsin 1, trypsin 2 and chymotrypsin A by mucus proteinase inhibitor, eglin c and aprotinin reveals that (i) the first protein is a potent inhibitor of chymotrypsin A (kass. = 1.4 x 10(6) M-1.s-1, Ki = 71 pM) but forms loose complexes with trypsin 1 (Ki = 0.5 microM) and trypsin 2 (Ki = 18 nM), (ii) eglin c does not inhibit the two trypsins but forms a tight complex with chymotrypsin A (kass. = 3.3 x 10(6) M-1.s-1, Ki < 0.1 nM) and (iii) aprotinin is a potent inhibitor of trypsin 1 (kass. = 1 x 10(6) M-1.s-1, Ki < 0.2 nM) and trypsin 2 (kass. = 2.4 x 10(5) M-1.s-1, Ki < 1 nM) but forms a loose complex with chymotrypsin A (Ki = 0.17 microM). These data, together with those published previously on human pancreatic elastase, suggest that a cocktail of aprotinin + eglin c might be a better intensive-care drug for acute pancreatitis than aprotinin alone, because it will efficiently inhibit all four human pancreatic proteinases. On the other hand, human gastric juice inactivates mucus proteinase inhibitor by pepsin-mediated cleavage. This indicates that the fraction of mucus proteinase inhibitor that reaches the stomach following aerosol delivery to cystic fibrosis patients does not reach the duodenum in an active form and, therefore, does not aggravate the pancreatic insufficiency of these patients.
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PMID:Inhibition of human pancreatic proteinases by mucus proteinase inhibitor, eglin c and aprotinin. 857 92

During two treatment periods (4 weeks each), serum immunoreactive trypsin (IRT), immunoreactive human lipase in stool (IRL), and chymotrypsin (CT) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion (72-h sampling). Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients (X = 13.7 +/- 9.0 g/24 h) in at least one study period. Stool fat excretion was highest in underweight adolescents and adults. Comparison of IRT and IRL with stool fat values showed no significant statistical correlation. IRT values revealed an inverse exponential correlation with age, with a steep decline at the age of 5 years. CT levels were very high in 14 of our 16 patients during supplementation therapy, whereas 2 patients showed subnormal CT values. We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion, stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis. Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate.
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PMID:Indirect parameters of pancreatic function in cystic fibrosis (CF) during a controlled double-blind trial of pancreatic supplementation. 878 90

We investigated the development of the exocrine pancreas in Cftr-/- mice in comparison with age-matched littermates (Cftr+/+, Cftr+/-) up to 100 d postnatally. Controls were weaned either to mouse chow or a liquid diet; Cftr-/- mice were weaned solely to a liquid diet. Solid-fed control mice gained weight and showed a progressive increase in pancreatic protein, DNA, amylase, lipase, trypsin, and chymotrypsin activities. Liquid-fed control mice showed similar postnatal somatic and pancreatic growth, except that amylase and lipase activities were lower than in the solid-fed controls. Cftr-/- mice exhibited significantly lower body and pancreatic weights than did controls. Pancreatic protein content and enzyme activities (notably amylase and lipase) were consistently lower than in the age-matched litter-mates fed either diet. The reduction in lipase activity in Cftr-/- mice was noted before weaning. We concluded that the liquid diet influenced postnatal exocrine pancreatic development in mice. However, a further reduction in postnatal pancreatic growth and enzymatic activities in the Cftr-/- mice was noted. These alterations could be due to the primary cystic fibrosis defect, although secondary factors, such as malnutrition induced by decreased dietary intake or abnormal absorptive capacity, may be responsible.
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PMID:Exocrine pancreatic alterations in long-lived surviving cystic fibrosis mice. 882 72

FK706, sodium 2-[4-[[(S)-1-[[(S)-2-[[(RS)-3, 3, 3-trifluoro-1-isopropyl-2-oxopropyl]aminocarbonyl]pyrrolidin -1-yl]carbonyl]-2-methylpropyl] aminocarbonyl] benzoylamino] acetate, C26H32F3N4NaO7, is a synthetic water-soluble inhibitor of human neutrophil elastase. This compound demonstrated a competitive and slow-binding inhibition of human neutrophil elastase with a Ki of 4.2 nM. In studies using synthetic substrates, FK706 inhibited human neutrophil elastase activity and porcine pancreatic elastase activity with respective IC50 values of 83 and 100 nM. FK706, however, inhibited more weakly, (IC50 values > 340 microM) other serine proteinases such as human pancreatic alpha-chymotrypsin, human pancreatic trypsin and human leukocyte cathepsin G. FK706 also effectively inhibited the hydrolysis of bovine neck ligament elastin (2 mg/ml final concentration) by human neutrophil elastase (4 microg/ml final concentration) with an IC50 value of 230 nM. FK706 protected animals against human neutrophil elastase (50 microg/animal)-induced lung hemorrhage with ED50 values of 2.4 microg/animal by intratracheal administration and 36.5 mg/kg by intravenous administration, respectively. Subcutaneous administration of FK706 significantly suppressed human neutrophil elastase (20 microg/paw)-induced paw edema in mice in a dose-dependent manner (47% inhibition at a dose of 100 mg/kg). These results suggest that FK706 would be a useful tool for investigating the role of human neutrophil elastase in inflammatory disorders associated with an excess of elastase, such as pulmonary emphysema, adult respiratory distress syndrome, septic shock, cystic fibrosis, chronic bronchitis and rheumatoid arthritis.
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PMID:Biochemical and pharmacological characterization of FK706, a novel elastase inhibitor. 938 82

Report on two babies, 5 and 6 months old with severe salt depletion were admitted to our hospital with fever and gastro-enteritis. One of them failed to thrive despite normal nutrition, the other one had a protracted gastro-enteritis. Both of them had a great loss of weight, a strong dehydration and were in reduced general condition but without any signs of coma or cerebral seizures. In the differential diagnosis cystic fibrosis with chronic loss of salt exacerbated during an infection, described as "Pseudo Bartter-Syndrome" was suspected. Both babies showed increased salt concentration in the sweat and decreased chymotrypsin in the stool.
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PMID:[Severe hyponatremia as diagnostic symptom of cystic fibrosis]. 944 20

Heparin tightly binds cathepsin G and so protects the enzyme from inhibition by alpha1-antichymotrypsin, alpha1-proteinase inhibitor and eglin c, three proteins which do not bind heparin [Ermolieff J., Boudier C., Laine A., Meyer B. and Bieth J.G. (1994) J. Biol. Chem. 269, 29502-29508]. Here we show that heparin no longer protects cathepsin G from inhibition when the enzyme is reacted with mucus proteinase inhibitor (MPI), a heparin-binding protein. Heparin fragments of Mr=4500 and 8100 and O-butyrylated heparin of Mr=8000 form tight complexes with cathepsin G (Kd=0.5-2.2 nM) and MPI (Kd=0. 4-0.8 muM) and accelerate the MPI-promoted inhibition of cathepsin G by a factor of 17-26. They also accelerate the inhibition of neutrophil elastase and pancreatic chymotrypsin. The rate acceleration is due to the binding of heparin to MPI. Butyrylation of heparin slightly decreases its affinity for cathepsin G and MPI but sharply decreases the ionic interactions between the positively charged proteins and the negatively charged polyanion. The butyrylated heparin derivative is the best rate accelerator: it increases the rate constant for the MPI-induced inhibition of cathepsin G and elastase by factors of 26 and 23, respectively. This, together with the fact that it has a good bioavailability and a very low anticoagulant activity, suggests that it might be an adjuvant of MPI-based therapy of cystic fibrosis.
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PMID:Heparin accelerates the inhibition of cathepsin G by mucus proteinase inhibitor: potent effect of O-butyrylated heparin. 949 8

We report a child with multiple target organ pseudohypoaldosteronism type 1 with frequent recurrent pulmonary infections caused by Pseudomonas aeruginosa and Pasteurella multocida and high levels of chloride in sweat, urine and nasal secretion. Repetitive faecal chymotrypsin samples have all shown pathological values in spite of no other sign of exocrine pancreas dysfunction. The similarities with cystic fibrosis and the importance of the salt content in bronchial fluid are discussed.
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PMID:Recurrent Pseudomonas bronchopneumonia and other symptoms as in cystic fibrosis in a child with type I pseudohypoaldosteronism. 1034 53


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