Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inter-alpha-trypsin inhibitor (ITI) consists of 3 polypeptides cross-linked by chondroitin sulphate, which is o-glycosidically linked to the smallest of the polypeptides, designated bikunin. Pre-alpha-trypsin inhibitor (p alpha I) consists of bikunin and a fourth polypeptide, also associated by chondroitin sulphate. Crossed immunoelectrophoresis (CIE) of plasma, using immunoglobulins to ITI, revealed 3 precipitation-lines, two of which increased in size during disease. Molecular mass determination by polyacrylamide gel electrophoresis showed that the immunoprecipitates contained mixtures of proteins. Therefore CIE is unfit for quantitation of the individual proteins related to ITI. Immunoblotting suggested that the plasma concentrations of p alpha I and of bikunin was increased in uraemia, rheumatoid arthritis and after trauma. The plasma concentrations of ITI and of p alpha I were decreased in a patient with endocarditis.
 ...
PMID:Inter-alpha-trypsin inhibitor and pre-alpha-trypsin inhibitor in health and disease. Determination by immunoelectrophoresis and immunoblotting. 170 71

One possible route to cataract formation may be via the carbamoylation of lens proteins due to increased concentrations of cyanate in the body resulting from uraemia associated with renal failure and with severe diarrhoea. Carbamoylation of gamma-II-crystallin, which is found in the lens core, could alter the surface charge network of the molecules, resulting in aggregation, increased light-scattering and hence cataract. We have attempted to locate the site(s) of carbamoylation in gamma-II-crystallin. gamma-II-Crystallin was isolated by gel chromatography and ion-exchange chromatography. gamma-II-Crystallin was then carbamoylated by incubation with potassium [14C]cyanate, followed by citraconylation and digestion with trypsin to give peptides that were separated by high-resolution ion-exchange chromatography. The amino acid compositions of the radioactive peptides were compared with the expected peptide composition for gamma-II-crystallin. The radioactive peptide compositions, which agreed with the theoretical peptides, all matched with the N-terminal region of gamma-II-crystallin and had in common the presence of the N-terminal glycine residue. It appears that the alpha-amino group of the N-terminal glycine was the main site of carbamoylation. This site forms part of the charge network on the surface of gamma-II-crystallin.
 ...
PMID:Site of carbamoylation of bovine gamma-II-crystallin by potassium [14C]cyanate. 259 Jan 75

We have previously shown that the incubation of normal rat adipose tissue with sera from nondialyzed, nondiabetic uremic patients reduces the transport and metabolism of glucose, in the absence and presence of insulin. In this study insulin-stimulated glucose metabolism by normal rat adipocytes was used as a bioassay to identify the resistance activity, assess the effect of chemical modification on it, and the clinical states associated with its production. The resistance activity was trypsin-labile and had an apparent isoelectric point between 6 and 7, but was not retained by either protein A or concanavalin A columns. The insulin resistance activity was decreased by coincubation with the protein synthesis inhibitor, cycloheximide. Purification to greater than 200,000-fold was attained by heating (100 degrees C) uremic serum, subjecting the supernatant to Sephadex G-25 chromatography and subsequent adsorption to DEAE at pH 7.8 and elution at pH 6.5. The partially purified resistance activity was retained within dialysis tubing of 1,000-mol wt cutoff but not within 2,000-mol wt cutoff. Hemodialysis of patients over 1 wk to 18 mo reduced significantly the amount of resistance activity in their sera. The resistance activity, present in most uremic patients, was not found in the sera of individuals with normal renal function but who were either obese, fasted, elderly or had type II diabetes mellitus. Thus, a circulating small molecular weight peptide, unique to uremia, induced insulin resistance by a protein synthesis-dependent mechanism.
 ...
PMID:Characterization and partial purification of a factor from uremic human serum that induces insulin resistance. 388 60

The blood content of the enzymes changes under narcosis. The atrophic alterations of the pancreas induced by ligation of its ducts, entail the reduction of the pancreatic enzymes content in the blood. This leads to an increase of the amylase and pepsinogen affinity with the blood plasma proteins participating in the transport of enzymes. In uremia disturbing the fermental homeostasis, the transport properties of proteins and erythrocytes change. Duodenectomy exerts no persistent or obvious effect on the content of pepsinogen, amylase, trypsin and its inhibitor in the peripheral blood plasma and temporarily reduces its lipolytic activity.
 ...
PMID:[Mechanisms stabilizing the concentration of intestinal gland hydrolases in peripheral blood]. 616 64

Proteolytic enzymes exist in plasma ultrafiltrates, concentrated dialysates, and urine fractions of patients with posttraumatic acute renal failure (ARF), as well as in urine fractions of patients with nephrotic syndrome and in concentrated dialysates of patients or routine dialysis therapy (RDT). Differences in the digestion pattern of phosphorylase kinase suggest the existence on different proteases. Plasma trypsin-binding capacity is reduced in RDT patients and is markedly decreased in patients with posttraumatic ARF compared with healthy subjects. Protein catabolism of plasma fractions of patients with posttraumatic ARF is inhibited in vitro by alpha 2-macroglobulin. Urinary alpha 1-antitrypsin inactivates added kallikrein in urine fractions of patients with posttraumatic ARF or nephrotic syndrome. Proteases may also be involved in the disturbances of carbohydrate metabolism of uremic patients. The role of proteolytic degraded phosphorylase kinase, muscle contractile proteins, hormone receptors, or pancreas islets on the pathogenesis of altered carbohydrate metabolism in uremia is discussed.
 ...
PMID:Role of proteases in hypercatabolic patients with renal failure. 620 1

Employing a sensitive semi-quantitative electrophoretic-technique on acid-deproteinized serum, we found two previously unrecognized trypsin inhibitors migrating as beta 2- and gamma-globulins, respectively. The two inhibitory bands were also detected in native serum. They were not seen in 3 healthy persons, but were found in patients with uremia, cancer, inflammatory diseases and collagenosis. Immunological investigations showed no cross-reaction with antibodies against seven well-known proteinase inhibitors. The two trypsin inhibitors also inhibited pancreatic elastase.
 ...
PMID:Slow migrating proteinase inhibitors in human serum. 656 23

Among the abnormalities in erythrocyte porphyrin metabolism already described in patients with chronic renal failure on hemodialysis, a decrease in blood aminolevulinate dehydratase activity has been reported, suggesting the presence in uremic plasma of an inhibitor of the enzyme. The aim of this work has been to isolate and characterize such an inhibitor. Blood samples from 105 patients with chronic uremia were collected; plasma was applied to Sephadex G-100 columns and the fraction with the highest inhibiting capacity was identified and purified by subsequent SDS-polyacrylamide gel electrophoresis, followed by electroelution and electroblotting. It was demonstrated that the factor present in plasma of uremic patients inhibited blood aminolevulinate dehydratase in a concentration-dependent manner; its inhibitory properties were abolished after heat, trypsin and TCA treatment indicating its peptidic nature. The purified inhibitor has an apparent molecular mass of 56.2 kD, it inhibits blood aminolevulinate dehydratase in a competitive way and the Ki value is 12x10(-6) M. The amino acid composition of the inhibitor has been determined and it has been found that its N-terminal amino acid is blocked. The isolated peptide may play a role in heme biosynthesis disturbances and in the pathogenesis of uremic anemia.
 ...
PMID:Inhibition of erythrocyte aminolevulinate dehydratase by a 56.2-kD peptide from uremic plasma. 1035 64

Peritoneal sclerosis has been induced in rodents in vivo by exposing the membrane to a variety of experimental interventions: asbestos, 0.1% chlorexidine, iron dextran, glucose degradation products, AGE deposits derived from uremia per se, sodium hypochlorite, lypopolysaccharide, low pH, pure water, silica or zymosan. With a few exceptions (pure water, chlorhexidine and low pH), the other substances mentioned operate setting out different degrees of oxidative stress. This short review describes several experimental interventions in rodents, aimed at acute exfoliation or long-term, sustained injury of the mesothelial monolayer performed by means of intraperitoneal injections of different oxidant agents. Acute exfoliation induced by deoxycholate resulted in a depopulated monolayer coincident with immediate alteration of the peritoneal permeability, evidenced by increased urea D/P ratio, higher glucose absorption rate, elevated albumin losses in the effluent and significant reduction of the ultrafiltration rate. In the long term (30 days), these manifestations of membrane failure persisted and coincided with substantial peritoneal sclerosis. Peritoneal sclerosis was also induced by IP injections of 0.125% trypsin and 6.6 mM/L solution of formaldehyde. Using the doughnut rat model of mesothelial regeneration, exposure to 4.25% glucose or 7.5% icodextrin solutions severely hampered repopulation of the monolayer, which was replaced by a thick sheet of fibrous tissue. It is concluded that peritoneal sclerosis derives mostly from sustained oxidative injury to the peritoneal membrane. Loss of the mesothelial monolayer is the first step in the chain of events leading to this complication.
 ...
PMID:A short review of experimental peritoneal sclerosis: from mice to men. 1577 May 97