Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antithrombin activities in 30 severely malnourished children and 40 normal children were estimated in clotting tests by thrombin neutralisation as anti-Xa and by a heparin antithrombin assay; and by immunodiffusion as alpha 2-globulin and alpha 1-antitrypsin. The patients' mean alpha 2-globulin was severely depressed, and there were less marked depletions in mean values for thrombin neutralisation, anti-Xa, and in the heparin antithrombin assay (which showed the flat curve thought to reflect a thrombotic tendency). The alpha 1-antitrypsin values were normal. The findings support the concept of antithrombin as the summation of alpha 2-globulin and alpha 1-antitrypsin (with alpha 2-macroglobulin); and the low values may be related to the high incidence of thrombosis reported in childhood malnutrition, although it was not seen in these patients.
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PMID:Antithrombin activities in childhood malnutrition. 11 90

The influence of PGI2 on the activity and on the inactivation of enzymes participating in blood coagulation (thrombin and Factor Xa) and fibrinolysis (plasmin) were investigated. According to the results PGI2 has no effect on the activity of Factor Xa and plasmin nor on the inactivation of these enzymes by antithrombin-III in the absence and presence of heparin at a concentration of PGI2 up to 400 micrograms/ml. An acceleration of the inactivation of thrombin by antithormbin-III was found in the presence of PGI2 within a concentration of 100-400 micrograms/ml without any effect on the heparin-accelerated inactivation of thrombin by antithrombin. We got similar results using clotting tests for the assay and the application of synthetic substrate for thrombin. This inactivation-accelerating effect of PGI2 on thrombin was only demonstratable at a concentration five magnitudes higher than that of the anti-aggregation effect on platelets.
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PMID:Effects of PGI2 on the inactivation of thrombin, factor Xa, and plasmin by antithrombin-III and heparin. 16 May 89

Heparin remains the most effective antithrombotic drug. It acts by combining with plasma antithrombin, thereby accelerating the neurtalisation of thrombin and other acitvated coagulation factors. Full-dose intravenous heparin is indicated in all cases of pulmonary embolism and established deep venous thrombosis, unless there exist compelling contraindications. Continuous intravenous infusion of heparin appears to be safer than intermittent injection. Low-dose subcutaneous heparin is effective in preventing the initial occurrence of thigh vein thrombi and in reducing the incidence of fatal pulmonary embolism in general surgical patients over the age of 40. The efficacy of low-dose heparin in preventing pulmonary emboli following hip surgery has not been established. The incidence of severe heparin-induced thrombocytopenia appears to be rising. Platelet counts should be performed in all patients receiving heparin by any mode of administration.
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PMID:Heparin Therapy: regimens and management. 31 90

Heparin is not suitable as an anticoagulant in the leucocyte migration test used to demonostrate the presence of migration inhibition factor (MIF) due to a rapid disappearance of the response after even a short storage of the blood. The use of defibrinated blood is highly recommended and defibrinated blood can be stored for at least 90 min without any diminution of the response. The change in response when using heparinized blood is not due to any direct effect of heparin, because heparin has no effect when added to defibrinated blood. However, heparin, added together with thrombin, is capable of abolishing the MIF effect completely. The basis for this phenomenon is most probably the binding of the heparin-antithrombin cofactor (AT III) to a complex with heparin and thrombin. The activity of MIF requires the presence of AT III, its esterase-inhibiting activity probably being crucial, in order to express MIF activity on macrophages. This mechanism forms a link between certain cellular immune reactions and the blood-clotting system.
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PMID:Migration inhibition factor and the blood clotting system: effects of defibrination, heparin and thrombin. 33 64

Human alpha-thrombin with high clotting activity and its proteolyzed derivative gamma-thrombin with virtually no clotting activity reacted in an essentially identical manner with antithrombin. The two enzyme forms bound proflavin with similar constants and showed identical behavior with small substrates. No significant differences were found for the antithrombin reactions (measured by proflavin displacement or active site titration) with respect to kinetics, extent of reaction, or effect of added heparin. The enzyme--antithrombin complexes could not be dissociated with sodium dodecyl sulfate (NaDodSO4) but the NaDodSO4-denatured complexes were dissociated by hydroxylamine treatment. The gamma-thrombin-antithrombin complex has an approximate molecular weight of 75 000 by disc gel electrophoresis as compared with 100 000 for the alpha-complex, consistent with the polypeptide structures of the two proteins. The gamma-thrombin--antithrombin complex did not inhibit clotting catalyzed by alpha-thrombin. In addition, fibrinogen did not affect the reaction of gamma-thrombin with antithrombin or antithrombin--heparin. Thus, the antithrombin and antithrombin--heparin reactions do not involve the fibrinogen recognition sites which are destroyed by proteolytic conversion of alpha-thrombin to the noncoagulant gamma form.
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PMID:Antithrombin reactions with alpha- and gamma-thrombins. 42 Jul 68

Preparations of low molecular weight porcine heparin with an average specific anticoagulant activity of 94 units/mg were fractionated into "active" and "relatively inactive" forms of the mucopolysaccharide of approximately 6000 daltons each. The active fraction was further subdivided into various species with descending but significant affinities for the protease inhibitor as well as decreasing but substantial anticoagulatn potencies. "Highly active" heparin (approximately 8% of the low molecular weight pool) possesses a specific anticoagulant activity of 350 +/- 10 units/mg. The relatively inactive fraction (67% of the low molecular weight pool) exhibits a specific anticoagulant activity of 4 +/- 1 units/mg. The binding of highly active heparin to antithrombin is accurately described by a single-site binding model with a KHep-ATDISS of approximately 1 X 10(-7) M. Variations in this binding parameter secondary to changes in environmental variables indicate that charge-charge interactions as well as an increase in entropy are critical to the formation of the highly active heparin-antithrombin complex. The interaction of relatively inactive heparin with the protease inhibitor is characterized by an apparent KHep-ATDISS of 1 X 10(-4) M. In large measure, this is due to small amounts of residual active mucopolysaccharide (0.5%). The ability of the highly active heparin to accelerate the thrombin-antithrombin interaction was also examined. We were able to demonstrate that the mucopolysaccharide acts as a catalyst in this process and is able to initiate multiple rounds of enzyme-inhibitor complex formation. The rate of enzyme neutralization is increased to a maximum of 2300-fold as the concentration of heparin is raised until the inhibitor is saturated with mucopolysaccharide. Further increases in heparin concentration result in a reduction in the speed of enzyme neutralization. This appears to be due to the formation of thrombin-heparin complexes. A mathematical model is given which provides a relationship between the initial velocity of enzyme neutralization and reactant concentrations.
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PMID:Fractionation of low molecular weight heparin species and their interaction with antithrombin. 42 27

Various clinical experiments have shown that women taking oral contraceptives have functional values of antithrombin 3 that are less than the values measured with the electroimmunoassay method for antithrombin 3. No final explanation for this occurrence is available. Since tests were performed on the same serum specimens, differences in antithrombin 3 concentrations in plasma and serum do not account for the difference between functional and immunologic values. Electroimmunoassay, unlike radioimmunoassay, does not measure both free and complexed antithrombin 3; therefore, if complexes between thrombin and antithrombin 3 were present, they did not contribute to over- or underevaluation of antithrombin 3. It is possible that an inhibitor is responsible. Results of these experiments point out the importance of measuring both functional properties and protein concentrations together.
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PMID:Effect of oral contraceptives on antithrombin III measurement. 45 6

Washed human platelets were solubilized and the proteins were separated by preparative gel electrophoresis in the presence of sodium dodecyl sulphate. The gel was cut into slices and the effect of the eluted proteins on the clotting of fibrinogen by thrombin was evaluated. The isolate from only one gel slice strongly inhibited the clotting of fibrinogen. The prolongation of the clotting time was dependent on the concentration of the protein and reached a plateau around 5 microgram. Gel electrophoresis of this isolate showed a prominent glycoprotein with an apparent Mr=150 000. Gel filtration studies with [125I]thrombin showed that the protein isolate bound a significant amount of thrombin which could be displaced with unlabelled thrombin. Another preparation from the same gel or purified gamma-globulin did not bind thrombin or prolong the clotting time of fibrinogen. Glycoprotein I was isolated from human platelets by affinity chromatography on lectin-Sepharose columns. The isolated glycoprotein prolonged the clotting of fibrinogen and bound [125I]thrombin which could be displaced by unlabelled thrombin. It is proposed that the high affinity receptor of thrombin on human platelets is glycoprotein I. In addition, the antithrombin activity of intact platelets is due to binding of thrombin to this glycoprotein.
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PMID:Thrombin receptors of human platelets: thrombin binding and antithrombin properties of glycoprotein I. 46 56

To clarify the action of dextran sulphate, a heparin analogue, in the clotting of fibrinogen by thrombin, determinations were carried out on the clotting activity, the release of fibrinopeptides from fibrinogen, and the hydrolytic activity of thrombin against a peptide chromogenic substrate in the absence or presence of antithrombin III (heparin cofactor). It was shown that dextran sulphate itself inhibited thrombin activity, and its inhibition was dependent on the molecular weight and the sulphur content of the dextran sulphate. Although heparin markedly enhanced the antithrombin activity of antithrombin III, dextran sulphate did not activate antithrombin III.
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PMID:Effect of dextran sulphates on thrombin activity. 46 1

The inactivation of thrombin and factor Xa by antithrombin was determined in the presence of heparin fractions of different molecular weights and with high affinity for antithrombin. The ability to potentiate the inactivation of either coagulation factor increased with increasing length of the polysaccharide chain.
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PMID:On the molecular-weight-dependence of the anticoagulant activity of heparin. 48 55


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