Enhancement by heparin of thrombin-induced antithrombin III proteolysis: its relation to the molecular weight and anticoagulant activity of heparin
Previous findings indicated that binding of heparin to antithrombin III (AT III) facilitates thrombin-induced proteolysis of the inhibitor. Researchers now studied this property of heparin in regard to its molecular weight and anticoagulant activity. Commercial heparin was resolved on Sephadex G-200 into six fractions of decreasing molecular weight. From each fraction high affinity (HA) heparin was isolated by chromatography on AT III-Sepharose and examined in reaction of alpha-thrombin with a molar excess of /sup 125/I AT III. Proteolysis of the inhibitor was assessed by SDS polyacrylamide gel electrophoresis. In the presence of the HA heparin from 18% to 38% of AT III participating in reaction appeared in the form of inactive 50,000-dalton fragment, as opposed to 7% of AT III fragmented in the absence of heparin. Although the ability to potentiate proteolysis was at its peak in the medium-molecular-size heparin fraction, the amount of degraded inhibitor relative to anticoagulant activity increased with decreasing molecular weight of the polysaccharide. These findings are consistent with the possibility that the ability of bound heparin to facilitate the cleavage of AT III by thrombin is generally less contingent upon secondary characteristics of the polysaccharide than the anticoagulant activity.
- Research Organization:
- Department of Medicine, University of Kentucky Medical Center Lexington
- OSTI ID:
- 5996824
- Journal Information:
- Thromb. Res.; (United States), Journal Name: Thromb. Res.; (United States) Vol. 28:3; ISSN THBRA
- Country of Publication:
- United States
- Language:
- English
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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARBOHYDRATES
CHEMICAL ANALYSIS
CHEMICAL BONDS
CHEMICAL PROPERTIES
CHEMICAL REACTIONS
COAGULANTS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HEPARIN
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MUCOPOLYSACCHARIDES
NORTH AMERICA
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HYDROLASES
POLYSACCHARIDES
PROTEINS
PROTEOLYSIS
QUANTITATIVE CHEMICAL ANALYSIS
RADIOISOTOPES
REACTION KINETICS
SACCHARIDES
SERINE PROTEINASES
THROMBIN
TRACER TECHNIQUES
USA