Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter VI. BIOCHEMISTRY OF PHYSIOLOGICAL FUNCTIONS AND SPECIALIZED TISSUES

CHAPTER 29. BIOCHEMISTRY OF BLOOD COAGULATION AND FIBRINOLYTIC SYSTEMS

29.3. ANTICOAGULANT BLOOD SYSTEM

Under normal physiological conditions, the fluid state of the Blood is maintained by the anticoagulant system, which consists of anticoagulants—compounds that counteract the intravascular activation of the coagulation cascade.

Anticoagulants act as inhibitors of specific Blood Coagulation protein factors. A decrease in the level of these inhibitors in human Blood Plasma leads to an increased tendency toward blood clotting and can result in thrombosis.

Antithrombins are blood Proteins that inhibit the catalytic activity of Thrombin. The most potent thrombin inhibitor is antithrombin III, a protein whose anticoagulant activity increases significantly in the presence of heparin. Antithrombin III is capable of binding to Serine proteinases of the blood coagulation enzyme cascade, blocking not only thrombin but also The activity of such factors,

as IX_a, X_a, XI_a, XII_a.

α₁-proteinase inhibitor (α₁-antitrypsin) is a glycoprotein of the plasma α₁-globulin fraction. This inhibitor exhibits a broad spectrum of antiproteinase activity, suppressing many serine proteinases, notably thrombin, as well as factors X_a and XI_a of the BLOOD COAGULATION SYSTEM.

α₂-Macroglobulin is a glycoprotein of the plasma α₂-globulin fraction and a proteinase inhibitor with broad substrate Specificity, effectively blocking serine, thiol, carboxy, and metalloproteinases. The concentration of α₂-macroglobulin in human blood plasma (up to 2.5 g/L) is the highest among all proteinase inhibitors. α₂-Macroglobulin acts as a thrombin inhibitor whose activity, unlike that of antithrombin III, does not depend on heparin. This inhibitor accounts for up to 25% of the total antithrombin activity of blood plasma.

Heparin is a heteropolysaccharide (glycosaminoglycan) that acts as a potent natural anticoagulant. Its molecule consists of repeating disaccharide units made up of sulfated D-glucuronic or L-iduronic acid residues and N-acetylglucosamine. Heparin occurs either as free polysaccharide chains or as Proteoglycans, which are proteins linked to multiple glycosaminoglycan chains.

Heparin is synthesized by mast Cells (heparinocytes) located in the Liver, Lungs, and along the walls of Blood Vessels. The anticoagulant mechanism of heparin involves the activation of antithrombin III: interaction with heparin induces a conformational change in antithrombin III, enabling it to bind to serine proteinases of the coagulation cascade and thereby block their catalytic activities.

Coumarins are natural (plant-derived) and synthetic anticoagulants that act as vitamin K antagonists. They function as indirect anticoagulants, opposing The formation of biochemically active (γ-carboxyglutamated) coagulation factors II, VII, IX, and X. In clinical practice, 4-hydroxycoumarin derivatives such as Neodicoumarin and Syncumar are used for the Prevention and Treatment of thrombosis.