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

---

Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The saliva of the tsetse, Glossina morsitans morsitans Westwood, has antithrombin anticoagulant activity and inhibits thrombin's esterolytic activity. It has no other detectable anticoagulant properties. The anticoagulant elutes in a single peak on Sephadex fraction, is immediately acting, heat and storage stable, and has a molecular weight of 11-13,000. Unlike heparin it is not neutralized by protamine sulphate or toluidine blue and does not require the co-factor, antithrombin III, for optimal anticoagulant activity. It has similar properties to hirudin, but does not elute with a protein peak upon Sephadex fractionation and has a slightly different molecular weight. Salivary gland homogenates contained neither a plasminogen activator nor fibrinolytic activity. The sera of rabbits used to maintain tsetses, which contained precipitating antibodies against saliva, did not neutralize the salivary anticoagulant in vitro. The properties of this anticoagulant suggest that it might be a potentially useful antithrombotic agent in man.
...
PMID:Effects of tsetse (Glossina morsitans morsitans Westw.) (Diptera: Glossinidae) salivary gland homogenate on coagulation and fibrinolysis. 50 76

The reaction between thrombin and antithrombin results in the formation of an inactive, stable, equimolar complex between the two proteins. However, under most reaction conditions several secondary complex forms, which have lower apparent molecular weights in dodecyl sulfate/polyacrylamide gel electrophoresis, appear concomitantly with or immediately following the production of the primary form of the complex. Purification of nascent, intact complex and treatment of this complex form with thrombin demonstrated that these subsidiary forms of antithrombin-thrombin complex may arise by proteolysis of the nascent complex by excess thrombin. Dissociation of such proteolytically modified complex preparations by hydroxylamine, and examination of the dissociation products by dodecyl sulfate/polyacrylamide gel electrophoresis suggested that degradation occurs primarily in the thrombin part of the complex, and only after prolonged proteolysis in its antithrombin moiety also. Incubation of antithrombin with several autolytically modified thrombin preparations showed that formation of subsidiary complex forms can also occur by an alternative route, i.e. between premodified thrombin forms and the inhibitor. In contrast, complex formation between thrombin and active forms of antithrombin, which have been modified by thrombin before complex formation, is unlikely, since no such active forms of antithrombin could be demonstrated.
...
PMID:Routes of thrombin action in the production of proteolytically modified, secondary forms of antithrombin-thrombin complex. 51 Mar 13

Secondary generalized hyperfibrinolysis was induced by thrombin infusion or batroxobin injection in rats. To follow intravascular fibrinolysis quantitatively, an electroimmuno-assay was used for determination of the fibrin degradation products formed. Anticoagulants (heparin, hirudin), antifibrinolytics (EACA, PAMBA, AMCA), and synthetic (APPA) and naturally occurring (aprotinin) protease inhibitors were studied with regard to their influence on secondary fibrinolysis. The potency and duration of action of the antifibrinolytics tested correspond to their antifibrinolytic activity measured in vitro and to their pharmacokinetics. Formation of degradation products is initiated after the appearance of fibrin monomer or fibrin, respectively. Due to their antithrombin action heparin, hirudin, and APPA prevent the thrombin-induced fibrin formation and thus the induction of secondary fibrinolysis. In contrast, formation of fibrin monomers caused by batroxobin is not influenced by thrombin inhibitors so that in this case formation of degradation products is not prevented.
...
PMID:[Pharmacologic influence on secondary generalized fibrinolysis]. 53 98

Influence of melphalan on some platelet functions, plasmatic coagulation and fibrinolysis "in vitro" was investigated, using different concentrations of the drug (25, 50 and 250 mug/ml). The lowest concentration slightly inhibited adrenaline and/or collagen-induced platelet aggregation. Following the highest concentration of the drug, strong inhibition of aggregation was recorded, regardless of the inducer used. Melphalan was also shown to inhibit release of aggregating activity and release of platelet factor 4, as well as availability of platelet factor 3 and platelet acid phosphatase. The intensity of inhibition depended on both, melphalan concentration and the time of preincubation. In contrast to this, adhesion of platelets to glass slide was not found to be influenced by melphalan. Similarly, melphalan did not induce (in any concentration) loss of LDH from platelet cytoplasma, while triton X-100 or freezing and thawing of platelets caused significant increase of LDH activity. From coagulation tests studied, only thrombin time and reptilase time was found to be moderately prolonged in the presence of melphalan. Authors assumed that melphalan acts as a specific inhibitor of release reaction and can induce an acquired thrombocytopathy. The platelet membrane is not damaged by the drug, as was confirmed by the investigation of LDH activity. Influence on coagulation indicates some antithrombin effect of the drug. Although presented results were obtained in vitro, analogous changes in vivo could be suspected. Thus, impairement of platelet functions might play a part in haemorrhagic complications accompanying, in some cases, melphalan therapy.
...
PMID:Influence of cytotoxic drugs on platelet functions and coagulation in vitro. IV. Melphalan. 57 17

Studies of 11 patients with haemorrhagic stroke revealed no significant change in kaolin cephalin clotting time, prothrombin time, thrombin time, PF 3 availability, platelet count and factor V and VIII during the first week. Plasma fibrinogen was significantly increased while factors VII + X were decreased (borderline significance). Prolongation of plasma recalcification time and decrease in heparin tolerance reached borderline significance. There was moderate, but significant, increase in serum antithrombin activity and plasma (euglobulin fraction) fibrinolytic activity.
...
PMID:Blood coagulation and fibrinolysis in haemorrhagic stroke. 58 May 8

Thrombin inactivation by antithrombin-III and heparin has been found to decrease in the presence of collagen, whereas thrombin activity and the rate of thrombin inactivation by antithrombin-III alone are not affected. Albumin, at the same concentration as collagen, does not influence either thrombin activity or thrombin inactivation by antithrombin-III or by antithrombin-III plus heparin.
...
PMID:Effect of collagen on thrombin inactivation by antithrombin-III and heparin. 61 87

Modification of 5--6 arginine residues of thrombin with 1,2-cyclohexanedione has resulted in the selective abolition of the heparin sensitivity of the enzyme's reaction with antithrombin-III, whereas the antithrombin-III sensitivity of native and modified thrombin was indistinguishable. It is suggested that heparin accelerates the thrombin antithrombin-III reaction by interacting with thrombin.
...
PMID:Decreased heparin sensitivity of cycholhexanedione-modified thrombin. 63 Nov 29

The inactivation of thrombin by heat and by its physiological inhibitor, antithrombin-III, shows quite different dependence on heparin concentration. Heparin at 250 microgram/ml protects thrombin against heat inactivation, and thrombin behaves heterogeneously in this reaction. In the absence of heparin, the thermodynamic activation parameters change with temperature (deltaH+ = 733 kJ/mol and 210 kJ/mol at 50 and 58 degrees C respectively). When heparin is present, heat inactivation of the protected thrombin species proceeds with deltaH+ = 88 kJ/mol and is independent of temperature in the same range. On the other hand, heparin at 0.125-2.5 microgram/ml accelerates the thrombin-antithrombin-III reaction. Thrombin does not show heterogeneity in this reaction and the time courses at any heparin concentration and any temperature between 0 and 37 degrees C appear to follow first-order kinetics. Activation enthalpy is independent of heparin concentration or temperature, deltaH+ = 82-101 kJ/mol, varying slightly with antithrombin-III concentration and thrombin specific activity. Heparin seems to exert its effect by increasing activation entropy. On the basis of these data we suggest a mechanism of action of heparin in the thrombin-antithrombin-III reaction which accounts for all the important features of the latter and seems to unify the different hypotheses that have been advanced.
...
PMID:Effect of heparin on thrombin inactivation by antithrombin-III. 70 77

It is proposed that the anti-coagulant activity of heparin is related to the probability of finding, in a random distribution of different disaccharides, a dodecasaccharide with the sequence required for binding to antithrombin. It is shown that this probability is a function of the degree of polymerization of heparin. The hypothesis has been been tested with a series of narrow-molecular-weight-range fractions ranging from 5,600 to 36,000. The fractions having mol.wts. below 18,000 (comprising 85% of the original preparation) followed the predicted probability relationship as expressed by the proportion of molecules capable of binding to antithrombin. The probability that any randomly chosen dodecasaccharide sequence in heparin should bind to antithrombin was calculated to 0.022. The fraction with mol.wt. 36,000 contained proteoglycan link-region fragments, which may explain the deviation of the high-molecular-weight fractions from the hypothetical relationship. The relationship between anti-coagulant activity and molecular weight cannot be explained solely on the basis of availability of binding sites for antithrombin. The activity of high-affinity heparin (i.e. molecules containing high-affinity binding sites for antithrombin), determined either by a whole-blood clotting procedure or by thrombin inactivation in the presence of antithrombin, thus remained dependent on molecular weight. Possible explanations of this finding are discussed. One explanation could be a requirement for binding of thrombin to the heparin chain adjacent to antithrombin.
...
PMID:The molecular-weight-dependence of the anti-coagulant activity of heparin. 74 19

The effect of some mono- and divalent cations was examined on thrombin--antithrombin reaction in vitro. It was found that 0--0.1 M sodium- or potassium chloride did not affect either thrombin or antithrombin activity; at higher concentrations thrombin activity decreased. Calcium chloride as well as magnesium chloride at concentrations from 0 to 0.5 M increased enzyme activity, whereas at higher concentrations the activity decreased. Thrombin inactivation by antithrombin was also accelerated at calcium or magnesium chloride concentrations above 0.04 M. Antithrombin was inactivated at pH 7.3 at 65 degrees C in some minutes and heparin failed to protect it against heat denaturation. Thrombin inactivation by antithrombin did not proceed at 0 degrees C in 60 min, but the interaction between thrombin and antithrombin was facilitated in the presence of heparin.
...
PMID:Some properties of human progressive antithrombin. 75 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---