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Coagulation Cascade Proteases

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Coagulation Cascade Proteases Background

About Coagulation Cascade Protease

The coagulation cascade proteases are a group of enzymes that play a crucial role in the process of bl

ood clotting, also known as coagulation. These proteases are responsible for the sequential activation of various clotting factors and proteins, leading to the formation of a stable blood clot.

The coagulation cascade can be divided into two main pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by factors present within the blood, while the extrinsic pathway is triggered by external factors such as tissue damage. Both pathways converge to activate a common pathway that ultimately results in the formation of a blood clot.

Several key proteases are involved in the coagulation cascade, including thrombin, factor Xa, factor IXa, and factor VIIa. Thrombin is a central protease in the cascade that converts fibrinogen, a soluble protein, into insoluble fibrin strands, forming the structural framework of the blood clot. Factor Xa and factor IXa are proteases that contribute to the activation of thrombin, while factor VIIa initiates the coagulation process.

The activity of these coagulation cascade proteases is tightly regulated to maintain the balance between clot formation and prevention of excessive clotting. Protease inhibitors play a crucial role in regulating the activity of these proteases. They act to inhibit specific proteases, preventing uncontrolled clotting and maintaining hemostasis.

Some examples of coagulation cascade protease inhibitors include tissue factor pathway inhibitors (TFPI), alpha-2-macroglobulin (A2M), and alpha-2-macroglobulin-like 1 (A2ML1). These inhibitors function by binding to the proteases and preventing their activity.

Understanding the mechanisms and interactions of coagulation cascade proteases and their inhibitors is essential for the diagnosis and management of bleeding and clotting disorders. It also provides insights into the development of anticoagulant therapies and treatments for coagulation-related diseases.

Ongoing research in this field aims to further elucidate the roles of coagulation cascade proteases and their inhibitors, leading to advancements in the prevention and treatment of clotting disorders and related conditions.

Schematic representation of the coagulation cascade and the fibrinolytic system.  Fig.1 Schematic representation of the coagulation cascade and the fibrinolytic system. (Loof T G, et al., 2014)
The coagulation cascade (blue arrows) can be activated during hemostasis via the intrinsic pathway (contact system; red arrows) or the extrinsic pathway (gray arrows) that ultimately converge on the common pathway of coagulation. Both pathways lead to the activation of factor X and subsequently of thrombin, which is required for the conversion of fibrinogen into fibrin and for activation of factor XIII. The fibrin clot is cross-linked and stabilized by factor XIII. Fibrinolysis (green arrows) is activated at the same time that the coagulation system but operates more slowly and is important for the regulation of hemostasis. During fibrinolysis, plasminogen is converted into plasmin that degrades the fibrin network. Coagulation factors are indicated with "F" followed by a roman numeral, an additional "a" denotes the activated form; HK, high molecular weight kininogen; uPA, urokinase plasminogen activator; tPA, tissue plasminogen activator.

Common Coagulation Cascade Proteases

Carboxypeptidase B2 (CPB2): CPB2, also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is a protease involved in the regulation of fibrinolysis, the process of breaking down blood clots. CPB2 acts by removing C-terminal lysine residues from partially degraded fibrin, which reduces the binding sites for plasmin, the primary enzyme responsible for clot dissolution. This inhibitory action of CPB2 helps to stabilize blood clots and prevent excessive bleeding.

Plasma Kallikrein (KLKB1): KLKB1 is a serine protease that plays a role in both the coagulation and fibrinolysis pathways. It acts as an activator of the intrinsic pathway, leading to the activation of factors XI and XII. Additionally, KLKB1 is involved in the production of bradykinin, a potent vasodilator and mediator of inflammation. It also activates plasminogen, contributing to the breakdown of blood clots.

Tissue Plasminogen Activator (PLAT): PLAT, also known as tPA, is a serine protease primarily involved in fibrinolysis. It converts plasminogen, an inactive precursor, into plasmin, an enzyme that breaks down fibrin clots. PLAT is released by endothelial cells and acts locally at the site of a blood clot to initiate clot dissolution. It plays a critical role in maintaining blood vessel patency and preventing excessive clot formation.

Urokinase (PLAU): Urokinase is a protease involved in the fibrinolytic system. It converts plasminogen into plasmin, promoting the breakdown of fibrin clots. Urokinase is produced by various cells, including endothelial cells and certain immune cells. It can be administered therapeutically to dissolve blood clots in conditions such as deep vein thrombosis or pulmonary embolism.

Proline-rich Acidic Protein 1 (PRAP1): PRAP1 is primarily synthesized in the liver and secreted into the bloodstream. In the coagulation cascade, PRAP1 acts as a serine protease that cleaves specific peptide bonds in proteins to activate them. It specifically activates the proenzyme form of coagulation factor XII (FXII) by cleaving it into its active form, factor XIIa. Factor XIIa then activates other downstream coagulation factors like factor XI (FXI) and factor IX (FXIX), leading to the formation of a stable blood clot. This process is essential for hemostasis and preventing excessive bleeding. The regulation of PRAP1 activity is tightly controlled to maintain a balance between effective hemostasis and avoiding harmful clot formation. Dysregulation of PRAP1 or other coagulation factors can result in bleeding disorders or thrombotic diseases.

These coagulation cascade proteases are essential components of the clotting and fibrinolysis systems. They contribute to the formation and dissolution of blood clots, maintaining the delicate balance between hemostasis and prevention of excessive clotting. Understanding their functions and regulation is crucial for diagnosing and managing clotting disorders and developing targeted therapeutic interventions.

Available Resources for Coagulation Cascade Protease

  • Creative BioMart offers a wide range of products related to coagulation cascade protease, such as recombinant proteins.
  • Whether you are a researcher in academia or the biopharmaceutical industry, we can provide customized services tailored to your specific requirements.
  • In addition to our products and services, we offer a wealth of resources for your reference. These resources cover various aspects of coagulation cascade protease, including pathways, protein function, interacting proteins, articles, research areas, and others. They are designed to help you deepen your understanding of coagulation cascade protease-related knowledge and facilitate the application.

Our Featured Products

Recombinant Human CPB2 protein, His-tagged
Recombinant Human PLAT, None tagged
Recombinant Human PLAU protein, His-tagged

If you have any questions, requirements, or cooperation intentions, please feel free to contact us. We very much look forward to working with you and helping you achieve research and commercial success.

Reference:

  1. Loof T G, Deicke C, Medina E. The role of coagulation/fibrinolysis during Streptococcus pyogenes infection[J]. Frontiers in cellular and infection microbiology, 2014, 4: 128.
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