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Blood flows as a fluid through the blood vessels to all the organ systems. Upon injury, blood vessel loss has to be prevented. This is done via blood coagulation. Under normal conditions, blood coagulation is a tightly regulated process:Rapid formation of a clot upon injuryLimited to the site of injurySecondary hemostasis is the conversion of soluble fibrinogen to insoluble fibrin by thrombin (IIa):Strengthens the platelet plugInduces adherence and activation of cells involved in vascular repairFibroblastsSmooth muscle cellsThrombin plays a key role in the conversion of fibrinogen to fibrin. It sometimes also is called coagulation factor IIa. Fibrinogen is also known as factor I and is very abundant in the plasma → normal levels are 1,5-3 gram/L. It consists of 2 symmetrical half-molecules, each consisting of 3 different polypeptide chains:Aα: linked together in the E-domain → the central partsBβ: in the D-domain → the outer partsγ: in the D-domain → the outer parts Fibrinogen is formed into fibrin as follows:Thrombin cleaves away fibrinopeptides A and B → fibrin monomers are formedFibrin monomers are very sticky2 fibrin monomers stick together → dimers are formedThis is done via H-bondsCoagulation factor XIIIa crosslinks different dimers → polymers are formedCoagulation FXIIIa = transglutaminaseThe enzyme factor XIII is converted into FXIIIa by thrombin (IIa)The crosslinks are formed between the D-domains of the fibrinThese are covalent bonds Thrombin is generated via the coagulation cascade. The coagulation cascade is a sequence of proteolytic reactions, which take place in parts of the surface of activated proteins. In each step, a pro-enzyme is converted to an enzyme, which activates the next pro-enzyme. These are slow reactions which can be sped up by co...
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