Thrombin is an enzyme involved in the blood coagulation process. It is a serine protease and is involved in the blood coagulation cascade. It converts fibrinogen to fibrin. Thrombin is formed from prothrombin in the blood coagulation pathway. It also catalyses various other reactions related to clotting.
Structure and Synthesis
Thrombin is a serine protease. It is an active enzyme produced from prothrombin by internal peptide bond cleavage. The molecular weight of prothrombin is 72,000 Da and of thrombin is 36,000 Da. The gene coding for thrombin is present on chromosome 11.
Thrombin is synthesised by the cleavage at two sites in prothrombin by activated factor X, i.e. Xa. The activated factor V, i.e Va is also involved in the process. It is called prothrombinase complex and it greatly enhances the activity of the factor Xa.
Mechanism of Action
Thrombin takes part in the blood-clotting pathway. It acts as both procoagulant and anticoagulant. As a procoagulant, it converts soluble fibrinogen to insoluble fibrin, which cross-links to form the blood clot. Thrombin also catalyses other reactions of blood coagulation pathways. Reactions catalysed by thrombin are:
Factor XI → XIa
Factor VIII → VIIIa
Factor V → Va
By activating factors V, VIII and IX, it regulates its own synthesis. It prevents fibrinolysis of fibrin clots by activating factor XI.
Factor XIII → XIIIa
By activating factor XIII, thrombin promotes cross-linking between fibrin fibres and stabilises the fibrin clot.
Thrombin also promotes platelet aggregation. It activates receptors present on the cell membrane of platelets.
Thrombin also acts as an anticoagulant. This is mediated by binding to thrombomodulin. Thrombomodulin is a membrane protein present on the surface of the endothelial membrane of the blood vessel. It stimulates the cascade of reactions leading to fibrinolysis.
When thrombin interacts with thrombomodulin protein, it converts thrombin to an anticoagulant enzyme from being procoagulant. Thrombomodulin acts as a cofactor and when bound to thrombin, the protein-C gets activated. Protein-C is an inhibitor of the blood coagulation pathway and it reduces blood coagulation.
Thrombin also plays an important role during inflammation or injury in vessels due to its chemotactic properties.
Thrombin is very important in the blood coagulation cascade. Thrombin is used for various purposes. E.g.
- Thrombin is used in research due to its high specificity of proteolysis.
- It is used for medicinal purposes such as in fresh frozen plasma, which is given to supplement patients with fewer clotting factors. Prothrombin complex concentrate is used to prevent and treat bleeding in case of haemophilia B.
- Anticoagulants such as Warfarin mostly manipulate prothrombin and inhibit the synthesis of thrombin.
- Thrombin along with fibrinogen is used as a binding agent for meat.
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