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

29.4. BLOOD FIBRINOLYTIC SYSTEM

Fibrinolysis is the enzymatic degradation of Blood clot fibrin, resulting in The breakdown of the thrombus. The functioning of the fibrinolytic system ensures the continuous dissolution of intravascular thrombi that may form on blood vessel walls due to factors activating the Blood Coagulation SYSTEM.

Fibrinolysis consists of two successive stages:

Stage I — The conversion of the inactive proenzyme plasminogen (profibrinolysin) into the active enzyme, the proteinase plasmin (fibrinolysin), which degrades the fibrin of the thrombus.

Plasminogen is a glycoprotein belonging to the β-globulin Class with a Molecular Weight of approximately 80 kDa, consisting of a single polypeptide chain.

Plasminogen activation and The formation of active plasmin occur through the proteolytic Cleavage of the internal peptide bond Arg₅₆₀ —► Val₅₆₁. Physiological activators of this glycoprotein include factor XII_a, as well as numerous tissue and vascular plasminogen activators. An important plasminogen activator is urokinase, which is synthesized in the Kidneys. Streptokinase, a protein found in β-hemolytic streptococci, has The ability to activate the glycoprotein without cleaving the intramolecular peptide bond.

Plasmin is a Serine proteinase with Trypsin-like enzymatic activity. It is a glycoprotein with a molecular weight of 80 kDa, composed of two polypeptide chains: heavy (A) and light (B). The physiological substrate of plasmin is fibrin; however, under in vitro conditions, the enzyme exhibits broad substrate Specificity, degrading various protein substrates such as fibrinogen, Complement protein factors, and casein.

Stage II — the degradation of fibrin, which forms The basis of the fibrin clot, into proteolytic peptide products. This process is catalyzed by the active plasmin generated During the first stage of fibrinolysis.

Soluble fibrin degradation products are excreted in the urine. An elevated level of fibrin breakdown products in the urine indicates excessive intravascular blood coagulation.

The continuous generation of plasmin from plasminogen in the blood serves as a physiological mechanism that counteracts intravascular thrombosis. On the other hand, excessive enhancement of fibrinolysis is prevented by the natural plasmin antagonist, the protein inhibitor glycoprotein α₂-antiplasmin. A hereditary decrease in blood α₂-antiplasmin concentration leads to increased bleeding tendencies.

In medical practice, the following pharmacological preparations of fibrinolytic system components are used for thrombus lysis and thrombosis Prevention:

1. Fibrinolysin (plasmin) — a preparation obtained from human blood profibrinolysin (plasminogen) via trypsin activation of plasminogen.

2. Urokinase — a preparation isolated from human Kidney Cells.

3. Streptokinase — a preparation derived from a culture of group C β-hemolytic streptococci.

4. Tissue plasminogen activator (tPA) — a preparation synthesized biotechnologically using Introduction/32.html">Genetic Engineering Methods.