Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

State of the anticoagulation system was studied after intravenous administration of trypsin at doses similar to the concentration of alpha-thrombin, activating chemoreceptors of vascular walls. Trypsin at doses 0.5 microM-3.7 microM did not affect the anticoagulation system as indicated by unaltered rate of nonenzymatic fibrinolysis. Occurrence of trypsin in blood led to generation of thrombin, which caused limited proteolysis of fibrinogen with subsequent increase in content of soluble fibrin, but did not stimulate the anticoagulation system. Distinct stimulation of the enzymatic fibrinolysis resulted from both liberation of plasmin due to direct proteolysis of plasminogen and unspecific release of the plasminogen activator after destruction of vascular endothelium. High doses of alpha-thrombin (70 NIH un per 1 ml of the preparation) did not activate the anticoagulation system but the total fibrinolytic activity was increased die to elevation in the ratio of enzymatic fibrinolytic activity. The data obtained suggest that the proteolytic activity of thrombin and trypsin is not responsible for the reflectory reaction of the anticoagulation system. High specificity of alpha-thrombin, caused by the presence in its structure of the recognizing sites of high molecular substrates, enables the enzyme to interact with chemoreceptors of vascular walls and to stimulate the anticoagulation system.
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PMID:[Enzymic and non-enzymic fibrinolysis during intravenous administration of trypsin]. 654 8

The reflex response of anticoagulating system was studied in perfusion of humorally isolated sinocarotid area with trypsin and alpha-thrombin in rabbits with intact neural connections. Trypsin (1.5 and 3.8 microM) does not induce a reflex release of heparin and plasminogen activator into the blood flow whereas alpha-thrombin (0.5 microM) activates the anticoagulating system which is evident from elongation of the recalcification period, augmentation of total fibrinolytic activity and non-enzyme fibrinolysis of the blood plasma. The level of plasminogen activator sharply rises in the blood with no significant augmentation of the plasmin activity. The data obtained suggest that the specific nature of thrombin in due to the area of high-molecular substrates binding rather than proteolytic activity. Chemoreceptors of the sinocarotid area fail to respond to thrombin after trypsin perfusion which suggests failure of the receptor apparatus after contact with trypsin.
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PMID:[Comparative analysis of the effect of alpha-thrombin and trypsin on the state of the anticoagulating system]. 668 61

Carboxypeptidase N (kininase I, arginine carboxypeptidase; EC 3.4.17.3) cleaves COOH-terminal basic amino acids of kinins, anaphylatoxins, and other peptides. The tetrameric enzyme of Mr 280,000 was purified from human plasma by ion-exchange and arginine-Sepharose affinity chromatography. Treatment with 3 M guanidine dissociated the enzyme into subunits of 83,000 and 48,000 molecular weight, which were separated and purified by gel filtration or affinity chromatography. When tested with hippurylarginine, hippurylargininic acid, benzoylalanyllysine, or bradykinin, the Mr 48,000 subunit was as active as the intact enzyme and was easily distinguished from human pancreatic carboxypeptidase B (EC 3.4.17.2). However, the Mr 48,000 subunit was less stable at acid pH or at 37 degrees C than the intact enzyme was. The carbohydrate-containing Mr 83,000 subunit was enzymatically inactive but stabilized the Mr 48,000 subunit at 37 degrees C. Trypsin, plasmin, and plasma or urinary kallikrein cleaved carboxypeptidase N into lower molecular weight active fragments, which were unstable at 37 degrees C. Cleavage of the Mr 48,000 subunit with the same enzymes increased activity and yielded fragments of Mr 29,000 or less. Antibodies to the Mr 83,000 of Mr 48,000 subunits crossreacted with the intact enzyme, and antibody to carboxypeptidase N also recognized both subunits. However, antibody to the Mr 83,000 subunit did not recognize Mr 48,000 subunit and antibody to the Mr 48,000 subunit did not crossreact with the Mr 83,000 subunit. Thus, this study indicates that carboxypeptidase N is composed of two immunologically distinct subunits, a Mr 48,000 subunit that is responsible for the enzymatic activity and a Mr 83,000 subunit that may stabilize the enzyme in blood.
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PMID:Isolation and characterization of the subunits of human plasma carboxypeptidase N (kininase i). 675 Jun 6

Inactive renin and active renin from human kidney and human plasma were prepared in highly purified forms by three steps of chromatography on Octyl-Sepharose, immunoaffinity chromatography, and pepstatin-amino hexyl Sepharose CL-4B. The inactive renin and active renin from human kidney had molecular weights of 51,000 and 44,000 as measured by a calibrated gel filtration column run with internal molecular weight standards. Molecular weights of plasma inactive renin and active renin were 56,000 and 51,000 respectively. Both inactive and active renins were found to be heterogeneous, consisting of several components with different isoelectric points. Renal inactive renin has higher pI values of 6.40, 6.10, 5.90, 5.61, and 5.40. Renal active renin has pI values of 5.73, 5.40, 5.25, and 5.13. The pI values of plasma inactive renin were 6.37, 6.08, 5.77, 5.36, and 5.25; of plasma active renin, 5.68, 5.40, 5.33, and 5.25. Trypsin activation and plasmin activation of plasma inactive renin produced an active enzyme with similar molecular weight but lower pI values. Acid activation of inactive renin did not change the molecular weight and pI values.
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PMID:Isolation and activation of inactive renin from human kidney and plasma. Plasma and renal inactive renins have different molecular weights. 702 7

Limulus amebocyte lysate was fractionated by heparin-Sepharose chromatography into four components (fractions A, B, C and D). Major coagulation factors, i.e., proclotting enzyme, coagulogen, and proclotting enzyme activating factor precursor (proactivator) in the lysate were eluted, respectively, in fraction A, fraction B and fraction C. Clotting enzyme activity was detected only following recombination of fraction A and fraction C in the presence of endotoxin. The conversion of proactivator to its active form (activator) was an endotoxin-dependent reaction and was inhibited by polymyxin B. Either proactivator is an endotoxin-sensitive factor or another endotoxin-sensitive factor, which activates proactivator, is present in fraction C. Optimal pH for proclotting enzyme activation by activator was broad and ranged from pH 6.0 to 8.0, while that for the endotoxin-mediated activation of proactivator was pH 7.0. No initial latent period was observed during activation of the proactivator or proenzyme. The activator was inhibited by benzamidine, leupeptin, soybean trypsin inhibitor and diisopropyl fluorophosphate, suggesting that the activator is a trypsin-type serine protease. Trypsin, but not thrombin, urokinase, plasmin, papain or alpha-chymotrypsin activated the proclotting enzyme. Therefore, limited proteolysis, i.e., of an arginyl- or lysyl-X bond(s), of the proenzyme molecule is probably involved in its activation.
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PMID:Fractionation of Limulus amebocyte lysate. Characterization of activation of the proclotting enzyme by an endotoxin-mediated activator. 713 84

Human pregnancy-associated plasma protein A (PAPP-A) inhibited significantly the proteolytic activity of bovine trypsin and human plasmin. Trypsin or plasmin treatment of PAPP-A resulted in the generation of a major 85 kDa component and the rapid cleavage of internal thiol esters. The results indicated that both of these serine proteinases bound in a 1:1 stoichiometry to PAPP-A. The PAPP-A-bound enzymes were found to be enzymatically active towards small synthetic substrates and inaccessible to inactivation by soybean trypsin inhibitor and alpha 1-proteinase inhibitor. The mechanism of proteinase inhibition was likely to be entrapment, as described for alpha 2-macroglobulin.
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PMID:Interaction of human pregnancy-associated plasma protein-A with serine proteinases. 758 86

The health of the respiratory tracts of 19 horses was studied for 11 months. The horses were placed into 3 groups (healthy, periodically diseased and continuously diseased) based on the measurements of blood gases, intrapleural pressure and on neutrophil content of tracheal mucus. Lysosomal enzymes (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase) and reflectors of the proteolytic system (plasmin, plasminogen, trypsin inhibitor capacity) were determined. beta-glucuronidase appeared to be a good indicator of the presence of disease of the respiratory system. High beta-glucuronidase values were seen in horses with elevated numbers of neutrophils, elevated arterial alveolar and intrapleural differences as well as in diseased horses during the stabling period. Trypsin inhibitor capacity seemed to be lower in the diseased respiratory system, probably due to the increased consumption of trypsin inhibitors.
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PMID:Beta-glucuronidase and trypsin inhibitor capacity of tracheal lavage fluid as indicators of seasonal airway irritation in the horse. 798 42

We have expressed a full-length cDNA clone encoding human factor D by using a baculovirus expression system. The purified recombinant protein reacted with Ab against native factor D, but was hemolytically inactive and slightly larger than factor D. These results suggested that the recombinant protein was the elusive zymogen of factor D. Amino acid sequencing demonstrated that the recombinant factor D consisted of two proenzyme forms with respective activation peptides, AAPPRGR and APPRGR. Catalytic amounts of trypsin converted recombinant profactor D to its enzymatically active form, exhibiting SDS-PAGE mobility and specific hemolytic activity similar to those of native factor D. About 90% of trypsin-activated recombinant profactor D had the same NH2-terminus as factor D. Human thrombin, kallikrein, and plasmin could also activate recombinant profactor D, but relatively high concentrations of these enzymes were required and the specific hemolytic activity of the "activated" profactor D was about one-third that of native factor D. Trypsin-activatable profactor D was also purified from the urine of a patient with Fanconi's syndrome. This native profactor D represented less than 1.0% of the total antigenic factor D in the patient's urine and had a Gly-Arg dipeptide as the activation peptide. Apparently, urine profactor D was produced by cleavage of pre-profactor D at Arg-(-3) by a serine protease with trypsin-like specificity, which probably is different from the putative leader peptidase that produces the recombinant profactor D. Urine profactor D was inhibited by diisopropyl fluorophosphate although the recombinant proenzyme was resistant to this inhibitor.
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PMID:Recombinant and native zymogen forms of human complement factor D. 814 40

Tritiated N alpha-acetyl-L-lysine chloromethyl ketone (ALCK) was synthesized on a laboratory scale for use as an active-site-directed affinity label in the fluorographic detection of proteases after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The synthesis involved acetylation of N epsilon-benzyloxycarbonyl-L-lysine chloromethyl ketone with [3H]acetic anhydride just before the removal of the benzyloxycarbonyl group. By this method, [3H]ALCK with a specific activity of 250 mCi/mmol was obtained as a crystal. Trypsin, thrombin, plasmin, papain, and clostripain were inactivated by ALCK according to first-order kinetics. For fluorographic detection of proteases, enzyme samples were allowed to react with [3H]ALCK and then resolved by SDS-PAGE. Proteases that reacted with [3H]ALCK could be detected with a sensitivity equivalent to or higher than that of Coomassie brilliant blue R-250 staining. A trypsin-like protease in Pronase, clostripain as a contaminant in a commercial preparation of Clostridium histolyticum collagenase, and cysteine proteases in Porphyromonas gingivalis could be detected.
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PMID:Synthesis of N alpha-[3H]acetyl-L-lysine chloromethyl ketone and its use in the fluorographic detection of proteases. 825 Feb 26

We investigated the effects of purified human urinary trypsin inhibitor (UTI) and fragments derived from UTI by proteolysis on the invasive potential of ovarian cancer cells (HOC-I) and gestational choriocarcinoma cells (SMT-ccl) using an in vitro reconstituted basement membrane invasion assay. These cells express cell-associated plasmin and functional uPA receptors that are partially occupied by ligands. SMT-ccl cells, which express threefold higher levels of cell-associated plasmin activity than HOC-I cells, showed approximately twofold increase in their invasive potential. For the invasion assay, HOC-I cells were primed with exogenous plasminogen, but SMT-ccl cells were not. Human leukocyte elastase (HLE)-digested UTI (22 kDa fragment; UTI-22) inhibited plasmin practically with the same strength as native UTI. Trypsin-digested UTI (20 kDa fragment; UTI-20), however, did not inhibit plasmin significantly. Treatment of cells with UTI or UTI-22 reduced the incidence of tumor cell invasive capacity, whereas the inhibitory effect of UTI-20 was not remarkable. The inhibitory effect on tumor cell invasion was dose-dependent and non-toxic; moreover, it was not mediated by inhibition of the tumor cell chemotactic response or of cell attachment to matrigel. These results indicate that inhibition of the proteolytic enzyme plasmin specifically reduced the invasive capacity of tumor cells in vitro.
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PMID:Urinary trypsin inhibitor (UTI) and fragments derived from UTI by limited proteolysis efficiently inhibit tumor cell invasion. 830 25


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