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Chemistry

ETD Archive

Theses/Dissertations

2008

Prothrombin

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Full-Text Articles in Physical Sciences and Mathematics

Factor Va Directs Catalysis By Factor Xa During Prothrombin Activation, Michael Anthony Bukys Jan 2008

Factor Va Directs Catalysis By Factor Xa During Prothrombin Activation, Michael Anthony Bukys

ETD Archive

Hemostasis occurs through the controlled activation and inactivation of clotting factors resulting in the arrest of bleeding without blockage to the vasculature, while thrombosis is the undesired formation of vascular blood clots, which adversely affects millions of people annually. Clotting factors circulate in blood as inactive zymogens, which are proteolytically activated in response to vascular injury, assembled into enzymatic complexes and in turn activate additional coagulation factors culminating in the production of thrombin from the enzymatic complex prothrombinase. The prothrombinase complex is composed of the activated enzymatic component factor Xa (fXa) complexed to the activated cofactor portion factor Va (fVa) …


Modeling The Human Prothrombinase Complex Components, Tivadar Orban Jan 2008

Modeling The Human Prothrombinase Complex Components, Tivadar Orban

ETD Archive

Thrombin generation is the culminating stage of the blood coagulation process. Thrombin is obtained from prothrombin (the substrate) in a reaction catalyzed by the prothrombinase complex (the enzyme). The prothrombinase complex is composed of factor Xa (the enzyme), factor Va (the cofactor) associated in the presence of calcium ions on a negatively charged cell membrane. Factor Xa, alone, can activate prothrombin to thrombin however, the rate of conversion is not physiologically relevant for survival. Incorporation of factor Va into prothrombinase accelerates the rate of prothrombinase activity by 300,000-fold, and provides the physiological pathway of thrombin generation. The long-term goal of …