Protein Chemistry. Structure, Properties, Research Methods - Shendryk A.N. 2022

Proteins of Blood and Muscle Tissues
Blood Coagulation System
Blood Coagulation System - Plasma Factors

The ability of Blood to clot and form a clot is a prime example of the highest level of biochemical self-regulation. The Theory of Blood Coagulation was first proposed in 1872 by A. Schmidt, a professor at the University of Dorpat (now Tartu). Its essence is as follows.

Blood coagulation is an enzymatic process. Three components are required for it to occur: fibrinogen, a fibrinoplastic substance, and Thrombin. The blood clotting process is a reaction producing fibrin from fibrinogen and a fibrinoplastic substance, catalyzed by thrombin.

Further research by Schmidt's school, as well as by Morawitz, Hammarsten, Spiro, and others, established that fibrin is formed from a single precursor: fibrinogen. The proenzyme of thrombin is prothrombin, and blood coagulation requires platelet thromboplastin and Calcium Ions. This blood coagulation theory is known as the Schmidt-Morawitz theory.

It is now established that the blood clotting process is much more complex and involves a significantly greater number of plasma and platelet components, known as clotting factors. Platelet-associated clotting factors are denoted by Arabic numerals, while plasma factors are denoted by Roman numerals.

Factor I is fibrinogen. It is a critical component of the clotting system. Fibrinogen consists of three pairs of non-identical peptide chains linked by Disulfide Bonds. Each chain carries an oligosaccharide group. The protein and carbohydrate components are linked via an asparagine-N-acetylglucosamine bridge. The length of the fibrinogen molecule is 450Ä, MW=330000-340000 Da. On paper Electrophoresis, fibrinogen migrates between ß- and γ-globulins. It is synthesized in the Liver.

Factor II is prothrombin. It is one of the main Plasma Proteins that determine blood clotting. The proteolysis of prothrombin yields the active clotting enzyme, thrombin. The concentration of prothrombin in plasma is 1.4-2.1 µmol/L. It is a glycoprotein containing 11-14% CARBOHYDRATES, including hexoses, hexosamines, and neuraminic acid. Based on its electrophoretic mobility, it belongs to α-globulins and has an MW = 68000-70000 Da. The molecule has an ellipsoidal shape (119 and 34 Å). The isoelectric point of purified prothrombin lies in the pH range of 4.2-4.4. It is synthesized in the liver with the participation of vitamin K. A specific feature is that a single prothrombin molecule binds 10-12 calcium ions, altering its conformation. The conversion of prothrombin to thrombin is accompanied by a sharp decrease in MW from 70000 to ≅35000 Da. It is hypothesized that thrombin is a large fragment of the prothrombin molecule.

Factor III is the tissue factor, or tissue thromboplastin. It is formed upon tissue injury and is a lipoprotein complex. It has a very large MW = 167,000,000 Da.

Factor IV consists of calcium ions. The removal of calcium ions (precipitation with oxalate or sodium fluoride) halts the blood clotting process. The optimal calcium ion concentration for coagulation is 1.0-1.2 mmol/L. Deviations in either direction slow down the clotting process. Calcium ions are required at almost all stages of blood coagulation.

Factor V is proaccelerin. It is a protein of the plasma globulin fraction and the precursor of the active factor, accelerin. It is synthesized in the liver.

Factor VII is antifibrinolysin or proconvertin, the precursor of convertin. The mechanism by which proconvertin converts to convertin remains poorly understood. Proconvertin is synthesized in the liver with the participation of vitamin K.

Factor VIII is antihemophilic globulin A. It is a necessary blood component for The formation of factor X. It is highly labile; in citrate-stabilized plasma stored for 12 hours, The activity of factor VIII decreases by 50%. A congenital deficiency of factor VIII is the cause of hemophilia A.

Factor IX is antihemophilic globulin B, or the Christmas factor. It participates in the formation of active factor X.

Factor X is the Stuart-Prower factor, named after the patients in whom its deficiency was first discovered. It belongs to α-globulins, with an MW = 87000 Da. It participates in the formation of thrombin from prothrombin. A deficiency in factor X leads to an increased blood clotting time. It is synthesized in the liver, and the synthesis process is sensitive to the body's vitamin K levels.

Factor XI is the Rosenthal factor, an antihemophilic protein factor. The deficiency of this factor in hemophilia C was first discovered by Rosenthal in 1953. It serves as the plasma thromboplastin antecedent.

Factor XII is the Hageman factor. It is a participant in the triggering mechanism of blood coagulation and stimulates fibrinolytic activity. Factor XII is activated upon contact with surfaces foreign to the body's internal environment, such as Skin, Glass, metal, etc. It is named after the patient who first exhibited blood clotting disorders associated with a factor XII deficiency.

Factor XIII is the fibrin-stabilizing factor. It is a plasma protein that stabilizes fibrin by participating in the formation of robust intermolecular bonds within polymerized fibrin. MW=330000-350000 Da. It consists of three peptide chains.