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)

The coagulating activity of thrombin was increased by 120% and the esterase activity--by 100% after incubation of thrombin with factor XIII. Factor XIII also stimulated generation of thrombin in the test of two-step estimation of prothrombin. The effect, arising from the interaction of factor XIII with thrombin, was specific for this enzyme because the esterase activity of trypsin was not increased during incubation of enzyme with factor XIII under the same conditions. The data obtained suggest that factor XIII or its fragment are effectors of enzymatic activity of thrombin in vitro and in vivo.
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PMID:[Factor XIII as a stimulator of thrombin activity]. 102 44

The effect of various forms of thrombin on certain platelet functions has been investigated. Partially purified bovine thrombin which is a mixture of multiple active forms of thrombin, was chromatographed to yield molecular species termed alpha-, beta-, and gamma-thrombin, each of which has varying degrees of fibrinogen clotting and esterase activities. A direct correlation was observed between the ability of the different forms of thrombin to clot fibrinogen and to influence platelet function. In general, thrombin with high fibrinogen clotting activity was also a potent inducer of platelet aggregation and the release reaction, while those species with low clotting ability were poor inducers of aggregation and release.
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PMID:Multiple active forms of thrombin: binding to platelets and effects on platelet function. 106 39

Amylase isoenzymes in serum, urine, saliva, jejunal juice, and pancreatic tissue were separated by isoelectric focusing. Isoamylase patterns obtained indicated that the majority of amylase activity in normal serum is of salivary gland origin. Pancreatic amylase is characteristically predominant in acute pancreatitis. The increased renal clearance of amylase in acute pancreatitis may be partly due to the increased proportion of the smaller molecular weight pancreatic amylase. However, a demonstrated increase in the renal clearance of salivary amylase in acute pancreatitis suggests a renal cause also. Autopsy pancreas samples devoid of TAME (p-tosyl arginine methyl ester) esterase activity (e.g. trypsin and plasma enzymes such as thrombin and plasmin) had isoenzyme patterns different to those samples with free proteolytic activity. Incubation of TAME esterase free pancreas with trypsin caused conversion of the former isoamylase pattern to one with the predominant isoenzymes focusing coincident with the predominant peak in serum from acute pancreatitis, jejunal aspirate, and TAME esterase positive autopsy pancreas. Such conversion suggests that pancreatic amylase is synthesized in a form different from that found in the intestinal lumen and serum.
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PMID:Studies on serum amylase in normal man and in acute pancreatitis. 107 39

Both the clotting and esterase activities of thrombin are inhibited by alpha1-proteinase inhibitor (alpha1-antitrypsin). The inhibition is a time-and temperature-dependent reaction which is proportional to the molar ratio of thrombin to inhibitor. Both the active-site serine residue of thrombin and the reactive-site lysine residue of alpha1-proteinase inhibitor are involved. alpha1-Proteinase inhibitor forms a 1:1 complex with thrombin that is comparable with the complex formed with trypsin and other proteinases. Incubation of the inhibitor with excess of thrombin, however, results in inactivation of nearly all the enzyme, even though only as much complex is formed as alpha1-proteinase inhibitor present. A portion of the remaining thrombin apparently aggregates. These results suggest that the mechanism for inhibition of thrombin may not be exactly the same as for trypsin, which is inhibited only to the extent to which complex is formed.
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PMID:Inactivation of human thrombin in the presence of human alpha1-proteinase inhibitor. 108 57

The plasma esterase inhibitors alpha2-macroglobulin, alpha1-antitrypsin, C1-inhibitor, antithrombin-heparin cofactor, and, as previously described, soybean trypsin inhibitor (Kunitz) and diisopropylphosphorofluoridate (9) enhance the response of guinea pig macrophages to migration inhibitory factor. To obtain this effect, macrophages are incubated with inhibitors prior to assay. The data suggest that (a) the enhancement of migration inhibitory factor response is due to the inhibition of esterases associated with the macrophage through a distinct active site on the inhibitors, and (b) that the active sites of antithrombin-heparin cofactor and soybean trypsin inhibitor, which interact with the macrophage enzymes, are different from the active sites of these inhibitors which interact with thrombin and trypsin respectively. Chemical modification of the active site of antithrombin-heparin cofactor for thrombin and of soybean trypsin inhibitor for trypsin does not affect their capacity to enhance the migration inhibitory factor response. From studies with thrombin, it was known that antithrombin-heparin cofactor has a heparin binding site. Addition of heparin was found to prevent the migration inhibitory factor-enhancing effect of antithrombin-heparin cofactor. The present results suggest that plasma esterase inhibitors may play a regulatory role in the response of macrophages to mediators of cellular immunity.
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PMID:Enhancement of migration inhibitory factor activity by plasma esterase inhibitors. 109 92

By means of DEAE-Sephadex A-50 column chromatography, Trimeresurus gramineus venom was separated into 12 fractions. Fraction 8 had marked anticoagulant action in the tests of whole blood clotting time, calcium clotting time and plasma prothrombin time. Fraction 8 was rechromatographed on Sephadex G-100, then on DEAE-Sephadex A-50 again, and finally on Sephadex G-100, and a single peak was obtained. The patterns of microzone and disc electrophoresis also showed a single band. A single symmetrical boundary with 1.70 Svedberg units was obtained by ultracentrifugation. The estimated molecular weight was 19 500. The isoelectric point was pH 4.5. Chemical analysis showed that the anticoagulant principle was a glycoprotein and that it was thermolabile. The anticoagulant activity of this purified principle was 3.5 times higher than that of the crude venom. Fraction 5 potentiated its anticoagulant activity to 10 times higher than that of the crude venom. This principle did not possess caseinolytic, tosyl-L-arginine methyl ester esterase, phospholipase A, phosphodiesterase, alkaline phosphomonoesterase, fibrinolytic, hemorrhagic or local irritating activities. The purified anticoagulant principle did not destroy fibrinogen, induce fibrinolysis, inactivate thrombin nor interfere with the interaction between thrombin and fibrinogen. However, a marked inhibition of prothrombin activation was caused by the anticoagulant principle. The inhibition of prothrombin activation was not due to the destruction of prothrombin or its activation factors, but due to an interference in the interaction between prothrombin and its activation factors because of the reversible binding of these factors with the anticoagulant principle of the venom.
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PMID:Purification and properties of the anticoagulant principle of Trimeresurus gramineus venom. 113 81

Thrombin binds with high affinity to specific cell-surface receptors on washed human platelets. We present experiments indicating that thrombin binding correlates withe the release reaction when binding is perturbed by anions. Marked differences in the affinity of human 125I-thrombin for platelets wer observed in various isotonic buffers at pH 7.4. At low concentrations of thrombin (0.001-0.01 U/ml), binding was 5-fold greater in Tris-sodium acetate and 12-fold greater in Tris-sodium cacodylate than in Tris-sodium chloride. These anion-induced changes in 125I-thrombin binding paralleled changes in [14C] serotonin release when both parameters were measured in the same platelets. Thus, equivalent release occurred for equal amounts of thrombin bound in all buffers, even though the thrombin concentration varied by up to 30-fold. After approximately 100 molecules of thrombin bound per platelet, complete release occurred in all buffers in 2 min. The effect of anions was specific for the thrombin-receptor interaction as there was no corresponding effect on the binding of erythroagglutinating phytohemagglutinin (E-PHA) to platelets nor on E-PHA or collagen-induced serotonin release. The various anions did not alter platelet morphology as judged by electron microscopy. The anions had no effect on thrombin esterase catalytic activity. In addition, the total number of thrombin receptors per platelet was approximately the same in all buffers. Thus anions alter the affinity between platelet thrombin receptors and a site on thrombin distinct from the catalytic site. We conclude that the thrombin receptor is essential for thrombin-induced platelet reactions.
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PMID:The perturbation of thrombin binding to human platelets by anions. 115 95

N-Butyrylimidazole has been found to be a potent inhibitor of purified bovine thrombin. The rate and extent of inhibition of thrombin by N-butyrylimidazole could be reduced by the presence of benzamidine, a competitive inhibitor, or by the ester substrate, p-tosyl-L-arginine methyl ester. Spectral studies of the reaction of N-butyrylimidazole with thrombin demonstrated the modification of approximately 1 mol of tyrosine/mol of enzyme at maximum inhibition. In addition to the reaction with tyrosine, N-butyrylimidazole also appears to react with a residue at the "active site" as judged by a decrease in the number of active sites available in the modified enzyme for titration with p-nitrophenyl-p'-guanidinobenzoate. The time course of ester hydrolysis by butyrylated thrombin showed a distinct lag phase suggesting partial reactivation of the enzyme under assay conditions. Partial reactivation of the modified enzyme also occurred spontaneously upon standing in 0.5 M NaCl but was much faster in presence of imidazole (0.03 M, pH 7.6). It is suggested that, in addition to reaction with tyrosine, there is a reaction of N-butyrylimidazole with either the histidine and/or serine residue at the active site of thrombin resulting in a derivative unstable under esterase assay conditions such as that described for the reaciton of N-acetylimidazole with trypsin (L. L. Houston and K. A. Walsh (1970), Biochemistry 9, 156).
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PMID:The reaction of bovine thrombin with N-butyrylimidazole. Two different reactions resulting in the inhibition of catalytic activity. 116 84

Conditions for the acylation of bovine prothrombin by maleic anhydride are worked out. The reaction is shown to modify not more than 95% of amino groups. The changes in hydrodynamic and electrophoretic properties testify about structural changes of prothrombin as a result of the modification of free amino groups. The activation of maleyl-prothrombin to maleyl-thrombin took place in 25% sodium citrate only in the presence of thrombin and the Xa factor. The increase of modified amino groups in prothrombin resulted in the decrease of the activity of generated maleyi-thrombin. The main fraction of maleyl-thrombin with free alpha-amino groups had a sedimentation coefficient of 2.1 S and possessed a residual esterase activity.
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PMID:[Activation of prothrombin, modified by maleic anhydride, some properties of N-maleyl-thrombin with free alpha-amino groups]. 123 12

The interaction of bovine thrombin [EC 3.4.21.5] with synthetic substrates and products was studied. The enzyme was purified from Parke-Davis topical thrombin. The purification process afforded some preparations with different clottin specific activities but with similar esterase specific activities. The preparation having highest clotting specific activity and that having lowest clotting activity were tentatively named thrombin-C and thrombin-E, respectively. Kinetic parameters for the hydrolysis of synthetic substrates and normality titrants were determined on the basis of active enzyme quantity, which was assayed by means of a fluorometric normality titrant. It was shown that thrombin-E was acylated by the substrates more slowly than thrombin-C, while deacylation proceeded at similar rates in the two preparations. The results were also compared with those obtained with bovine trypsin [EC 3.4.21.4]. The acylation rates of both thrombin preparations were markedly lower than that of trypsin, while the deacylation rates of the former were only slightly lower than that of the latter. The effects of various product-type inhibitors, such as benzyloxycarbonyl-, benzoyl-, and tosyl-L-arginine, were also examined. Thrombin was affected by these inhibitors not competitively, though trypsin was inhibited competitively.
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PMID:Comparison of the catalytic properties of thrombin and trypsin by kinetic analysis on the basis of active enzyme concentration. 124 85


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