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

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

By devising and applying quantitative methods for the assay of thrombin and autoprothrombin C and by developing techniques for their purification, it was possible to obtain information about the function and properties of antithrombin. The inhibitor is a protein for which the initial purification steps consist of removing fibrinogen from plasma by heating to 56 degrees for 3 min, removing prothrombin complex by absorption on barium carbonate, absorbing the antithrombin on aluminum hydroxide, and eluting with phosphate buffer. Antithrombin is limited in its capacity to neutralize thrombin activity, and, under some conditions, the rate of inhibition was accelerated, but equivocal results were involved. Heparin cofactor was found to be essential for retarding the formation of thrombin, and, by inference, it is essential for retarding the formation of autoprothrombin C. Heparin cofactor and antithrombin III are the same. Thrombin absorbs on fibrin, and this has been referred to as the "antithrombin I effect." Interference with the thrombin-fibrinogen reaction by mixtures of antithrombin III and heparin is called the "antithrombin II henomenon." The acceleration of thrombin inactivation at the time thrombin forms is called the "antithrombin IV effect." It was discovered that antithrombin III neutralizes thrombin, as well as autoprothrombin C. The inhibitor and the enzyme form a mutual depletion system. To assay for antithrombin III, a standard quantity of thrombin (about 1,100U/ml) was reacted with antithrombin III for 2 hr. The percent thrombin inactivated was then measured. In random samples of human blood, a wide range of antithrombin III concentration was found. The inhibitor is relatively stable in plasma and serum. It is not changed in concentration when Dicumarol therapy is instituted. Ether extraction of plasma reduces antithrombin III activity. Seitz filtration of plasma did not remove activity. Under special conditions, antithrombin III enhances esterase activity of thrombin. Under special conditions, thrombin regenerates from the thrombin-antithrombin III complex. Antithrombin III neutralizes the activity of prethrombin-E and thrombin-E; consequently, an active histidine center found in the B1 chain of thrombin is not essential for the binding of antithrombin. Autoprothrombin II-A activity was neutralized by antithrombin III. Autoprothrombin C was found to be neutralized by antithrombin III; the amounts required varied with the molecular forms of autoprothrombin C. Thrombin and autoprothrombin C apparently occupy the same binding sites on antithrombin III. An equation was developed to account for all the known characteristics of antithrombin III functions. The kinetic aspects of thrombin neutralization were found to correspond exactly with those of autoprothrombin C. Antithrombin III is a high-capacity inhibitor of the two most powerful enzymes in blood coagulation.
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PMID:Antithrombin III: a backward glance o'er travel'd roads. 4 4

The effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three alpha-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-alpha-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma alpha2-macroglobulin. The effect on plasma alpha1-antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-alpha-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.
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PMID:Effect of anabolic steroids on plasma antithrombin III. alpha2 macroglobulin and alpha1 antitrypsin levels. 5 96

Antithrombin III, purified to homogeneity according to polyacrylamide gel disc electrophoresis and immunoelectrophoresis, inhibited the activity of purified factor IXa and Xa, whereas factor VII was not inhibited either in the active or in the native form. Antithrombin III is the single most important inhibitor of factor Xa in plasma. Factor Xa does not, however, reduce the activity of antithrombin III against thrombin.
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PMID:The effect of antithrombin III on the activity of the coagulation factors VII, IX and X. 6 31

Changes of prekallikrein in the cases with DIC were investigated, i.e., DIC cases including disseminated metastasis of gastric cancer, acute promyelocytic leukemia and endotoxin shock. Therefore, the trigger substances for this paper were the pathologic cells of the leukemia, the cultured well differentiated adenocarcinoma cells and endotoxin. (1) The lysates of the pathologic cells of the leukemia and the cultured cells showed prekallikrein activation. Endotoxin showed prekallikrein activation via factor XII. (2) Serine proteases (factor Xa, thrombin, plasmin and trypsin) activated prekallikrein in the plasma and the purified prekallikrein. (3) Antithrombin III, aprotinin and FOY inhibited prekallikrein activation. Antithrombin III was promoted by heparin in its inhibitory effect.
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PMID:Changes of prekallikrein in the cases with disseminated intravascular coagulation syndrome. 16 Jan 91

Antithrombin III is one of the main inhibitors in the blood coagulation mechanisms. Thrombin and factor Xa are slowly inactivated by it, as well as other serine proteinases of the coagulation mechanisms. Heparin tremendously accelerates the inhibitory function of antithrombin III. In the process antithrombin III activity is also reduced. Heparin retards the thrombin-fibrinogen reaction, but otherwise the effectiveness of heparin as an anticoagulant depends on antithrombin III in laboratory experiments, as well as in therapeutics. The activation of prothrombin is inhibited, and any thrombin or other vulnerable protease that might generate becomes inactivated. The measurement of antithrombin III concentration in blood is now achieved by research methods, as well as by methods that are practical for routine use. The tests require either thrombin or factor Xa as substrate, and could be specific for antithrombin III. There are congenital as well as acquired deficiencies of antithrombin III. The inhibitor is also found in tissues.
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PMID:Antithrombin III. Theory and clinical applications. H. P. Smith Memorial Lecture. 34 19

During normal pregnancy, the concentrations of many of the clotting factors rise, thereby increasing the potential to generate fibrin. There is also evidence of increased thrombin activity during normal pregnancy which sharply increases during placental separation. Antithrombin III, the main inhibitor of thrombin and activated factor X, shows no compensatory rise during pregnancy but increases during the puerperium. Plasminogen and antiplasmin concentrations rise during pregnancy but systemic fibrinolytic activity, as measured by the euglobulin lysis time, is markedly depressed during pregnancy; the reduced fibrinolytic activity returns to non-pregnant values very soon after delivery. The loss of fibrinolytic activity is presumed to be loss of plasminogen activator, because when this is added in excess in the urokinase sensitivity test, the fibrinolytic response is normal. The capacity for localized fibrinolytic activity is not lost, however, because fibrinolytic degradation products are slightly raised during pregnancy. The overall pattern is one of increased coagulant and reduced fibrinolytic capacity during pregnancy which may protect the pregnant woman against the haemostatic challenge of placental separation.
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PMID:Blood clotting and fibrinolysis in pregnancy. 38 69

Anticoagulants in the form of heparin, dipyridimole, steroids, prostaglandin E1, Macrodex, and antithrombin III were administered in separate experiments prior to endotoxin infusion in the dog. The pattern of disseminated intravascular coagulation (DIC) developed consistently when endotoxin alone was administered. Heparin dosages from 1 to 10 mg/kg did not influence the appearance of thrombocytopenia but effectively eliminated the decrease in fibrinogen levels ordinarily found. Antithrombin III (AT III), obtained from the National Red Cross, administered in a dose designed to provide a doubling of the circulating AT III, reduced the fibrinogen utilization to a similar degree as heparin without affecting the platelet loss. Dipyridimole, as administered, was ineffective in this model, and did not alter the development of thrombocytopenia or the hypofibrinogenemia. Steroids, Macrodex, and prostaglandin E1 had minimal effect on the coagulopathy. Our finding would suggest that the endotoxin effect on dog platelets id direct, and not mediated by thrombin, and that the role of heparin in the clinical management of DIC should be considered only in instances in which renal complications exist.
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PMID:Endotoxin-induced intravascular coagulation (DIC) and its therapy. 40 May 81

Thrombocytin, a serine protease from Bothrops atrox venom, caused platelet aggregation and release of platelet constituents at a concentration of 10(-7) M and clot retraction at a concentration of 2 x 10(-9) M. Thrombocytin was slightly more active when tested on platelets in plasma than on washed platelets suspended in Tyrode--albumin solution. Thrombin was 5 times more active than thrombocytin when tested on platelets in plasma and 50 times more active when tested on washed platelets. The patterns or release induced by thrombocytin and thrombin were similar. Prostaglandin E1 (10(-5) M) produced complete inhibition of platelet release induced by thrombocytin and thrombin. Indomethacin (10(-4) M) was without any effect. Antithrombin III, in the presence of heparin, inhibited the action of thrombocytin on platelets and on a synthetic peptide substrate (Tos-Gly-Pro-Arg-pNA.HCl). formation of an antithrombin III--thrombocytin complex was demonstrated on NaDodSO4--polyacrylamide gel electrophoresis. Hirudin and alpha 1-antitrypsin did not inactivate thrombocytin. Thrombocytin had a low fibrinogen-clotting activity (less than 0.06% that of thrombin). Thrombocytin also caused progressive degradation of the alpha chain of human fibrinogen, and it cleaved prothrombin, releasing products similar to intermediate 1 and fragment 1 produced by thrombin. Thrombocytin activated factor XIII by limited proteolysis and increased the procoagulant activity of factor VIII in a manner analogous to that of thrombin.
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PMID:Thrombocytin, a serine protease from Bothrops atrox venom. 2. Interaction with platelets and plasma-clotting factors. 47 69

Blanket serial controls are not necessary in low-dosage heparin treatment. It would, in any case, be difficult under normal clinical conditions and would run counter to the whole conception of low-dose heparin treatment. However, in problem cases with an increased thrombo-embolic risk, sensitive methods for monitoring the heparin effect are recommended. A study on 150 patients has indicated that the most sensitive method is the use of chromogenic substrates. Thrombin time, using low-concentration thrombin solution of 1.5 NIH units/ml, thrombelastogram and activated partial thromboplastin time are less sensitive. Antithrombin III levels should be determined in all cases of increased heparin tolerance. With reduced antithrombin III levels and higher body weight an increase of the standard dose from 5000 U.S.P. units heparin t. i. d. subcutaneously to 7500 U.S.P. units t. i. d. should be considered.
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PMID:[Does low-dosage heparin treatment require serial haematological controls? (author's transl)]. 47 60

The precise quantitation of activated factors in human factor IX concentrates has been accomplished with the use of recently developed, specific assays for factors IXa, Xa, and thrombin. The assay for factor IXa, which measures the initial rate of 3H-factor-X activation, was shown to be specific for factor IXa in the concentrates. Activated factor IX concentrates contained 1.0-2.3 microgram/ml of factor IXa; whereas the assays of unactivated concentrates were negative (less than 0.2 microgram/ml). The assays of factor Xa and thrombin, which measure the initial rate of p-nitroaniline release from S-2222 and S-2238, respectively, showed similar small amounts of factor Xa (4-34 ng/ml) and thrombin (12-76 ng/ml) in the activated and unactivated concentrates. The nonactivated partial thromboplastin time of the concentrates correlated significantly with the factor IXa content, but not with factor Xa or thrombin. Antithrombin III antigen in 3 of 4 concentrates was several-fold higher than antithrombin III activity, suggesting the presence of antithrombin III complexed with activated factors. These results support the hypothesis that the degree of activation of factor IX concentrates is related primarily to the concentration of factor IXa, which may be responsible for the thrombogenicity of these concentrates in some clinical settings.
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PMID:Activated clotting factors in factor IX concentrates. 49 95


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