Mechanism of potentiation of antithrombin III and heparin cofactor II inhibition by sulfated xylans.

  title={Mechanism of potentiation of antithrombin III and heparin cofactor II inhibition by sulfated xylans.},
  author={L. Carson and V. Doctor},
  journal={Thrombosis research},
  volume={58 4},
Kinetic analyses of antithrombin III (AT-III)-thrombin or heparin cofactor II (HC-II)-thrombin or AT-III-factor Xa interactions were carried out in the absence or in the presence of one of the sulfated xylans or unfractionated heparin or low molecular weight (LMW) heparin utilizing chromogenic substrates. These studies demonstrated that under pseudo first order conditions the inhibitions were proportional to the AT-III or HC-II concentrations used and the apparent second order rate constants… Expand
Effect of sulfated xylans during the interaction of [125I]-thrombin with antithrombin III or heparin cofactor II of human plasma
Summary[125I]-Labeled thrombin was incubated with human plasma and its interactions with the two plasma protease inhibitors antithrombin III (AT-III) or heparin cofactor II (HC-II) were investigatedExpand
Antithrombin activity of a fucan sulfate from the brown seaweed Ecklonia kurome.
Results indicated that the antithrombin activity of C-II was mediated by HC II and not by AT III, and that the polysaccharide bound to fibrinogen, thereby blocking thrombin action, and also that its directThrombin inhibition was very weak. Expand
Anticoagulant properties of semisynthetic polysaccharide sulfates.
Several naturally occurring polysaccharides were purified and subsequently sulfated by chlorosulfonic acid-pyridine complex and exhibited antithrombic (anti-TT) properties similar to Heparin but were less effective than heparin in inhibiting APTT or PT. Expand
Fluorescence and circular dichroism studies during the interactions of sulfated polysaccharides with antithrombin III.
A comparison of the near ultraviolet (UV) circular dichroism (CD) spectrum of AT-III alone and during its interaction with oat spelts xylan sulfate (OSXS) showed enhancements of the two aromatic amino acid regions corresponding to phenylalanine and tryptophan. Expand
The effects of danaparoid, dalteparin and heparin on tissue factor-induced experimental disseminated intravascular coagulation and bleeding time in the rat
Findings suggest that danaparoid may be useful for the prevention of DIC and has less tendency to cause bleeding than dalteparin or heparin, probably as a result of its weaker ability to inhibit platelet aggregation. Expand
Effect of Xylan Sulfates on Coagulation of Human Blood Plasma
Sulfated derivatives of xylan (isolated from Bétula pubéscens wood) with average molecular weight ~34 kDa, sulfur content of 11.3-17.5%, a degree of substitution of 0.74-1.64 are anticoagulants ofExpand
Flow synthesis, characterization, anticoagulant activity of xylan sulfate from sugarcane bagasse.
This work provides a novel method for the synthesis of xylan sulfate with high molecular weight and controllable degree of substitution and offers new opportunities for the production of other functional polysaccharide derivatives under the flow reaction conditions. Expand
Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network
A multi-bypass microfluidics ladder network design with dimensions mimicking venules is utilized to study patterns of blood platelet aggregation and fibrin formation under complex shear, suggesting a specific correlation between microvascular geometry and thrombus formation dynamics under shear. Expand
Antioxidant and protease-inhibitory potential of extracts from grains of oat
Abstract The most of important crops cultivated for production of foods and feeds could be considered as plants possessing nutraceutical or medically interesting compounds, especially if can be eatenExpand
Derivatization and Characterization of Xylan from Oat Spelts
Xylan is the predominant hemicellulose component in the residues of annual plants, e.g., in oat spelts xylan amounts to 35-40% of the total mass. For our investigation xylan was separated throughExpand


Mechanism of potentiation of antithrombin III [AT-III] inhibition by sulfated xylans.
The sulfated xylans were more effective than heparin or SP-54 in potentiating the AT-III inhibition of amidolysis of H-D-Phe-Pip-Arg-pNa by thrombin (IIa), and an interaction between larchwood xylan sulfate and IIa which may potentiate an interactions between AT- III and IIA is suggested. Expand
The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin.
It is demonstrated that binding of heparin to antithrombin is required for the mucopolysaccharide-dependent enhancement in the rates of neutralization of thrombin, factor IXa, factor Xa, or plasmin by the protease inhibitor. Expand
Mechanisms for Inhibition of the Generation of Thrombin Activity by Sulfated Polysaccharides a
Observations indicate that the presence of trace thrombin activity is critical for efficient prothrombin activation by both the intrinsic and extrinsic pathways. Expand
Anticoagulant Action of Heparin
It is proposed that heparin acts to accelerate inhibitor function by binding to antithrombin and inducing an allosteric modification in it, which renders the arginine in its reactive site more accessible to the serine in the active centre of thrombin4. Expand
Reactive site peptide structural similarity between heparin cofactor II and antithrombin III.
Heparin cofactor II was purified 1800-fold from human plasma to further characterize the structural and functional properties of the protein as they compare to antithrombin III, and the similarities in primary structure suggest that heparin coFactor II may be an additional member of the superfamily of proteins consisting of alpha 1-antitrypsin and ovalbumin. Expand
The inhibition of activated bovine coagulation factors X and VII by antithrombin III.
  • J. Jesty
  • Chemistry, Medicine
  • Archives of biochemistry and biophysics
  • 1978
The decay of Factor X a deviates from pseudo-first-order kinetics and a final equilibrium is reached, suggesting reversibility, and Factor VII and the two-chain activated form, α-Factor VII a , and the tissue factor-Factor VIII a complex are not significantly inhibited by plasma levels of antithrombin III, in the either the presence of heparin. Expand
Pentosan polysulphate: activation of heparin cofactor II or antithrombin III according to molecular weight fractionation.
Three fractions of high, average and low molecular weights tested in clotting assays showed relative potencies corresponding to those observed in the purified systems, and concentration-dependent profiles indicated binding to antithrombin III and thrombin was a requisite of activation. Expand
The purification and mechanism of action of human antithrombin-heparin cofactor.
It is suggested that heparin binds to the inhibitor and causes a conformational change which results in a more favorable exposure of the arginine reactive site, allowing a rapid interaction with thrombin. Expand
Comparison of the inhibition of thrombin by three plasma protease inhibitors.
Comparison of the second-order rate constants and the normal plasma levels of the three inhibitors demonstrates that, under the in vitro conditions utilized, antithrombin III is five times and alpha2-macroglobulin is one-third as effective as alpha1-antitrypsin in the inhibition of thrombin. Expand
Structure of the antithrombin-binding site in heparin.
Compositional analysis based on separation and identification of deamination products reduced with sodium boro[3H]hydride showed that nonsulfated L-iduronic acid occurred in larger amounts in high-affinity heparin than in low-Affinity heParin; furthermore, this component was concentrated in the antithrombin-binding regions of the high- Affinity Heparin molecules. Expand