blood coagulation, intrinsic pathway

Definition

Target type: biologicalprocess

A protein activation cascade that contributes to blood coagulation and consists of the interactions among high molecular weight kininogen, prekallikrein, and factor XII that lead to the activation of clotting factor X. [GOC:add, GOC:mah, GOC:pde]

The intrinsic pathway of blood coagulation is initiated by contact activation, a process triggered by exposure of blood to collagen and other negatively charged surfaces. This exposure leads to the activation of factor XII (Hageman factor), which is a zymogen (inactive precursor) circulating in the blood.

Factor XII, upon contact with collagen, undergoes a conformational change, becoming activated to factor XIIa. Factor XIIa then activates factor XI, another zymogen, transforming it into factor XIa. Factor XIa, in turn, activates factor IX, another zymogen, converting it to factor IXa.

The activation of factor IX is a key step in the intrinsic pathway. Factor IXa, along with calcium ions and phospholipid surfaces, forms a complex with factor VIIIa (activated factor VIII). This complex is known as the "tenase complex," and it functions to activate factor X, another zymogen, into factor Xa.

Factor Xa, along with calcium ions and phospholipids, forms a complex with factor Va (activated factor V). This complex is called the "prothrombinase complex," and it serves as the final enzyme in the intrinsic pathway. The prothrombinase complex converts prothrombin, a zymogen, into thrombin, a powerful enzyme that cleaves fibrinogen, a soluble protein, into fibrin, an insoluble protein.

Fibrin monomers, formed by thrombin cleavage of fibrinogen, spontaneously polymerize into long fibrin strands. These strands become crosslinked by factor XIIIa (activated factor XIII), forming a stable fibrin meshwork that traps platelets and other blood components, forming a clot.

The intrinsic pathway is a complex and tightly regulated process. It involves a cascade of enzymatic reactions, each dependent on the activation of the previous factor. This cascade allows for a rapid amplification of the coagulation response, ensuring an efficient and timely formation of a clot to stop bleeding.

The intrinsic pathway is also subject to several regulatory mechanisms, including the activation of inhibitors, such as antithrombin III, and the presence of cofactors, such as protein C and protein S. These regulatory mechanisms ensure that the coagulation process remains tightly controlled and that excessive clot formation is prevented.'
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Proteins (1)

Compounds (82)