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)

1. The fate of corticotrophins in a trypsin-dispersed rat adrenal-cell assay system was investigated with a view to establishing whether differences in the rate of inactivation might contribute to potency differences observed between analogues. 2. Corticotrophin-(1-24)-tetracosapeptide and to a lesser extent synthetic 1-39 corticotrophins were found to be inactivated during incubation with cell suspension. 3. Peptide fragments were isolated by using [[(3)H(2)]Tyr(23)]corticotrophin-(1-24)- tetracosapeptide as a marker. The fragments indicate a peptidase with a predominantly tryptic specificity. 4. The peptidase is present in the extracellular fluid and is released from cells when they are damaged. 5. Cells were fractionated on an albumin gradient. Cells from the zona fasciculata and the zona intermedia or reticularis were present in fractions which produced fluorogenic steroids in response to corticotrophin. 6. Purification of the cells by centrifugation through albumin decreased degradation by peptidases, so that if the assay is carried out with a dilute suspension of purified cells peptide breakdown should not affect the observed potencies of adrenocorticotrophin analogues. 7. No binding of [[(3)H(2)]Tyr(23)]corticotrophin-(1-24)- tetracosapeptide to cells could be detected at low concentrations of the peptide. This indicated that less than 120 receptors/cell are occupied during stimulation by a dose that would elicit approx. 80% of the maximal response.
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PMID:Fate of corticotrophins in an isolated adrenal-cell bioassay and decrease of peptide breakdown by cell purification. 436 38

1. A neutral peptidase, previously shown to be located in the brush border of the proximal tubule, and assayed by its ability to hydrolyse [(125)I]iodoinsulin B chain was purified from rabbit kidney. 2. The starting material for the purification was a microsomal pellet prepared from a homogenate of cortical tissue. The membrane-bound enzymes were solubilized by treatment with toluene and trypsin. About half the neutral peptidase activity was released by this treatment in a form that no longer sedimented with the microsomal pellet and which penetrated polyacrylamide gels when subjected to disc electrophoresis. Other treatments with detergents or proteolytic enzymes either inactivated the peptidase or failed to convert it into a genuinely soluble form. 3. Chromatography with successive columns of Sephadex G-200, DEAE-cellulose and hydroxyl-apatite yielded an enzyme that was free of other brush-border peptidase activities and which was homogeneous on disc electrophoresis and ultracentrifugation. 4. The purified enzyme attacked [(125)I]iodoglucagon at a rate comparable with that for [(125)I]iodoinsulin B chain. It did not appear to attack proteins (insulin, albumin and casein) that had been similarly iodinated. 5. Unlabelled insulin B chain and unlabelled glucagon were substantially hydrolysed by the endopeptidase, whereas insulin and albumin released only trivial amounts of ninhydrin-reacting material. The resistance of insulin to attack by endopeptidase, even after prolonged incubation, was confirmed by biological and immunoassay. 6. The specificity of the peptidase was determined by analysis of the products after incubating unlabelled insulin B chain, and some oligopeptide substrates, including pentagastrin, with the enzyme. All of the bonds readily cleaved were those involving the alpha-amino group of hydrophobic residues, i.e. x-Leu-, x-Val-, x-Tyr-, x-Phe- and x-Met-, provided that the residues were not C-terminal. 7. The enzyme showed only endopeptidase activity. Substrates suitable for aminopeptidases, carboxypeptidases or esterases were not attacked.
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PMID:The purification and specificity of a neutral endopeptidase from rabbit kidney brush border. 442 92

The enzymatic hydrolysis of whole gliadin has been studied in vitro using sequential treatments by pepsin, trypsin, and pancreatin. Amino-terminal pyroglutamic acid-peptides were formed at each stage of the digestion process and the concentration of these peptides increased as the hydrolysis proceeded. Digests were further fractionated on columns of AG 50W-X8 or SE-Sephadex. Enzymic digests and selected column fractions were analyzed with pyrrolidonecarboxylate peptidase. Each digest or fraction was degraded further by this peptidase. Enzyme activity was greatest towards peptic-tryptic-pancreatic digests, peptic-tryptic digests, peptic digests, and undigested gliadin, in that order. The stability of lysosomal membranes to synthetic L-pyroglutamic acid, L-pyroglutamyl-L-alanine, L-pyroglutamyl-L-proline, and to selected fractions of the enzymic digests was tested. Each treatment ruptured lysosomal membranes. Findings are discussed in relation to the normal catabolism of gliadin and the alterations that may occur in certain pathological states.
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PMID:In vitro digestion of gliadin by gastrointestinal enzymes and by pyrrolidonecarboxylate peptidase. 610 31

Rats were fed semipurified diets which contained either 20% cellulose, Solka Floc, (HF) or no fiber (C) for 10 days. In the intestinal contents, the HF group had lower activity per milligram contents of trypsin, chymotrypsin, amylase, lipase and total proteolytic activity. Total activity of enzymes in the intestinal contents was also lower, except for chymotrypsin and leucine amino peptidase. Bile acid levels per milligram were lower in the HF group but the total amount was greater. The total weight of intestinal contents was greater in the HF group and total amount of protein present was elevated. The results indicate that a source of dietary fiber, cellulose, can affect the availability of enzymes and bile acids in the small intestine.
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PMID:Changes in small intestinal digestive enzyme activity and bile acids with dietary cellulose in rats. 615 11

Black widow spider venom gland extract was found to contain significant peptidase activity. Aliquots of the venom gland extract incubated at 37 degrees inactivated substance P (SP) and bradykinin but not angiotensin II or the enkephalins. The peptide inactivation was proportional to the duration of the incubation and the amount of extract used. Analysis of the peptides on high pressure liquid chromatography demonstrated that the loss in biological activity of SP and bradykinin in the longitudinal muscle of the guinea pig ileum was correlated with cleavage of the peptides into several fragments. Kinetic studies revealed that SP was initially split into two fragments but that these products underwent further degradation into smaller peptides. The optimal pH for the peptidase activity was 6.5. At 0 degree the enzymatic activity was undetectable, and it was irreversibly destroyed by incubation at 100 degrees for 5 min or by pretreatment of the extract with 100 microM diisopropyl fluorophosphate. In addition, the gland extract preparation hydrolyzed artificial substrates designed to detect trypsin or chymotrypsin-like activity.
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PMID:Hydrolysis of substance P and bradykinin by black widow spider venom gland extract. 618 58

The pre-treatment serum activities of several proteinase-like peptidases and the proteinase inhibitors, alpha 1-antitrypsin (alpha 1AT) and alpha 2-macroglobulin (alpha 2M), have been determined in 102 women with breast cancer and compared with those in 20 women with benign disease and in 30 healthy women of cancer bearing age. There were no significant differences in serum proteinase-like peptidase activities associated specifically with breast cancer. However, trypsin-like and plasmin-like activities were significantly lower than normal in women with breast disease. Serum alpha 1AT and alpha 2M levels were higher in patients with breast cancer than in healthy women or women with benign breast disease. These results indicate that, at presentation, breast cancer is not associated with abnormal serum levels of the proteinase-like peptidases studied, possibly as a result of an increase in the concentration of proteinase inhibitors.
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PMID:Serum proteinase-like peptidase activities and proteinase inhibitors in women with breast disease. 620 Mar 26

Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amounts of activity were also found in two other tumors (carcinoid and small cell carcinoma of lung) unassociated with GH hypersecretion. Each of the tumors contained somatostatin-like immunoreactivity but the levels did not correlate with the net biologic expression of the tumor. Sephadex G-75 gel filtration indicated the GH-releasing activity to have an apparent molecular size of slightly greater than 6,000 daltons. The GH-releasing activity was adsorbed onto DEAE-cellulose at neutral pH and low ionic strength, from which it could be eluted by increasing ionic strength. The GH-releasing activity was further purified by high pressure liquid chromatography using an acetonitrile gradient on a cyanopropyl column to yield a preparation that was active at 40 ng protein/ml. Partially purified GH-releasing activity, from which most of the bioactive somatostatin had been removed, increased GH release by pituitary monolayer cultures to five times base line. Enzymatic hydrolysis studies revealed that the GH-releasing activity was resistant to carboxypeptidase, leucine-aminopeptidase, and pyroglutamate-amino-peptidase but was destroyed by trypsin and chymotrypsin, indicating that internal lysine and/or arginine and aromatic amino acid residues are required for biologic activity and that the NH2-terminus and CO9H-terminus are either blocked or not essential. The results provide an explanation for the presence of GH-secreting tumors in some patients with the multiple endocrine neoplasia syndrome, type I, and warrant the addition of GH-releasing activity to the growing list of hormones secreted by tumors of amine precursor uptake and decarboxylation cell types.
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PMID:Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. 624 40

Angiotensin I converting enzyme (kininase II, peptidyl dipeptidase, ACE) was purified by reverse immunoadsorption from a membrane fraction of the human kidney. ACE is very likely a transmembrane peptidase. Treatment of the membrane-bound enzyme with trypsin releases a low mol. wt. fragment (greater than 10,000), which is probably the anchor peptide inserted into the plasma membrane. Antibody to ACE was used to localize it in the CNS where it is bound to plasma membrane of neuroepithelial cells in structures such as the globus pallidus or substantia nigra. Radioimmunoassay indicated that ACEs of endothelial, epithelial and neuroepithelial origin are immunologically identical. Direct radioimmunoassay also showed that there is a strong negative correlation between plasma enzyme level and pulmonary diffusing capacity of sarcoid patients. Finally, in addition to various peptides, homogeneous human ACE cleaves fluorogenic substrates where the C-terminal amino acid is replaced with nitrobenzylamine.
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PMID:Human converting enzyme. 631 67

An islet cell tumor, characterized by proinsulin level significantly elevated above normal human pancreas, has been found to contain insulin- and glucagon-degrading activity. Examination by chromatography on Sephadex G-75 of the degradation products formed from insulin showed A chain, and B chain rich-A chain aggregate as previously found with rat pancreatic islets. There was, however, little conversion of A chain to low molecular weight components indicating that insulinoma peptidase that has been found to degrade glucagon at about pH 6.8 degraded that A chain to a markedly lower rate. In contrast to the insulin-degrading activity, which was activated by glutathione in the presence of EDTA, the peptidase activity was not affected by the thiol compound. The activity of the peptidase was markedly inhibited by chelating agents, i.e., EDTA and o-phenanthroline, whereas chymotrypsin and trypsin inhibitors, i.e., TOS-PheCH2Cl, TOS-LysCH2Cl, soybean and pancreas trypsin inhibitor were found to have no effect.
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PMID:Thiol-protein disulfide oxidoreductase and peptidase activities in insulinoma tissue. 632 44

Two metal dependent proteases were investigated in rabbit uterus using a synthetic substrate, 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gin-D-Arg (Dnp-peptide). One was extracted by homogenization in 50 mM Tris-HCl/0.25% Triton X-100/100 mM CaCl2, pH 7.4, from rabbit uterus, and the other from the insoluble fraction by heating at 60 degrees C for 4 min in 50 mM Tris-HCl/100 mM CaCl2, pH 7.4. Both enzymes were partially purified by gel filtration, ion-exchange chromatography and chromatofocusing, and further characterized. The soluble enzyme was a metal dependent peptidase, and hydrolysed 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg as well as Dnp-peptide. Its molecular weight was about 7.0 X 10(4), and the cleavage sites for Dnp-peptide were Gln-Gly and possibly Gly-Ile in the ratio of 3:1. On the other hand, the enzyme extracted from the insoluble fraction was present as a latent form, and was found to be activated by 4-aminophenylmercuric acetate but not by trypsin. The activated enzyme hydrolysed gelatin, in addition to Dnp-peptide, indicating that the enzyme is a gelatinase. The molecular weight was about 7.4 X 10(4) for the active form, and the cleavage site for Dnp-peptide was only the Gly-Ile bond. The rabbit uterine metal dependent peptidase obtained here had negligible activity on gelatin, but once it had been cleaved by the above gelatinase, the presence of metal dependent peptidase accelerated the action of gelatinase. Thus, the actions of both enzymes on gelatin were found to be synergistic.
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PMID:Partial purification and characterization of gelatinase and metal dependent peptidase from rabbit uterus and their synergistic action on gelatin in vitro. 632 84


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