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The catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36,000 Da. Structurally, it is a member of the large PA clan of proteases. Prothrombin is composed of four domains; an N-terminal Gla domain, two kringle domains and a C-terminal trypsin-like serine protease domain.
To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg 271 and the other after Arg 320. [1] Although it has been shown that factor Xa can activate prothrombin when unassociated with the prothrombinase complex, the rate of thrombin formation is severely decreased under such circumstances.
Further, the final common pathway scheme implies that prothrombin is converted to thrombin only when acted upon by the intrinsic or extrinsic pathways, which is an oversimplification. In fact, thrombin is generated by activated platelets at the initiation of the platelet plug, which in turn promotes more platelet activation.
Prothrombin fragment 1+2 (F1+2), also written as prothrombin fragment 1.2 (F1.2), is a polypeptide fragment of prothrombin (factor II) generated by the in vivo cleavage of prothrombin into thrombin (factor IIa) by the enzyme prothrombinase (a complex of factor Xa and factor Va). [1] [2] [3] It is released from the N-terminus of prothrombin. [3]
Factor V a binds to prothrombin and Factor X a, increasing the rate at which thrombin is produced by four orders of magnitude (10,000x). Inactivation of Factor V a thus practically halts the production of thrombin. Factor VIII, on the other hand, is a cofactor in production of activated Factor X, which in turn converts prothrombin into thrombin.
It is therefore the first member of the final common pathway or thrombin pathway. It acts by cleaving prothrombin in two places (an Arg-Thr and then an Arg-Ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex.
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Prothrombin activator is a complex of a dozen blood coagulation factors that functions in catalyzing prothrombin into thrombin. Prothrombin activator is released in the body by a cascade of chemical reactions in response to damage in a blood vessel.