Biomaterial Database

Covalent complexes between low molecular weight heparin fragments and antithrombin III - inhibition kinetics and turnover parameters. 1983

M Hoylaerts, and E Holmer, and M de Mol, and D Collen

Two high affinity heparin fragments (Mr 4,300 and Mr 3,200) were covalently coupled to antithrombin III (J. Biol. Chem. 1982; 257: 3401--3408) with an apparent 1:1 stoichiometry and a 30--35% yield. The purified covalent complexes inhibited factor Xa with second order rate constants very similar to those obtained for antithrombin III saturated with these heparin fragments and to that obtained for the covalent complex between antithrombin III and native high affinity heparin. The disappearance rates from plasma in rabbits of both low molecular weight heparin fragments and their complexes could adequately be represented by two-compartment mammillary models. The plasma half-life (t1/2) of both low Mr-heparin fragments was approximately 2.4 hr. Covalent coupling of the fragments to antithrombin III increased this half-life about 3.5 fold (t1/2 congruent to 7.7 hr), approaching that of free antithrombin III (t1/2 congruent to 11 +/- 0.4 hr) and resulting in a 30 fold longer life time of factor Xa inhibitory activity in plasma as compared to that of free intact heparin (t1/2 congruent to 0.25 +/- 0.04 hr).

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D005170	Factor X	Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder.	Autoprothrombin III,Coagulation Factor X,Stuart Factor,Stuart-Prower Factor,Blood Coagulation Factor X,Factor 10,Factor Ten,Stuart Prower Factor,Factor X, Coagulation
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D006493	Heparin	A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.	Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000990	Antithrombin III	A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.	Heparin Cofactor I,Antithrombin III-Alpha,Atenativ,Heparin Co-Factor I,Kybernin,Serpin C1,Thrombate III,Antithrombin III Alpha,Antithrombin IIIAlpha,Cofactor I, Heparin,Heparin Co Factor I
D015951	Factor Xa	Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.	Autoprothrombin C,Coagulation Factor Xa,Factor X, Activated,Thrombokinase,Activated Factor X,Blood Coagulation Factor X, Activated,Factor 10A,Factor Ten A,Factor Xa, Coagulation