Mann Kenneth G
Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Chest. 2003 Sep;124(3 Suppl):4S-10S. doi: 10.1378/chest.124.3_suppl.4s.
The generation of the enzyme thrombin from its precursor prothrombin is the central event of the blood coagulation process, which is essential to hemostasis and the culprit in thrombosis. Thrombin is produced by a complex series of proteolytic events that are initiated when cryptic tissue factor interacts with plasma factor VIIa to initiate the complex series of events leading to the formation of the blood coagulation enzyme complexes that lead to the efficient generation of the enzyme. During these processes, thrombin contributes to both the generation of the catalysts involved in its ultimate production and to the catalysts that lead to attenuation of its production. Thrombin-catalyzed events both enhance and diminish the process of thrombin generation, which is down-regulated by stoichiometric and dynamic inhibitory processes. The combinations of intensities of activation and inhibition processes provide tight regulation of the hemostatic process, establishing reaction thresholds, essentially leading to an "on/off" switch. This review provides a brief summary of the evolution of knowledge with respect to present-day concepts of thrombin generation via the tissue factor pathway and its regulation.
凝血酶从其前体凝血酶原的生成是血液凝固过程的核心事件，这对于止血至关重要，同时也是血栓形成的罪魁祸首。凝血酶由一系列复杂的蛋白水解事件产生，当隐匿性组织因子与血浆因子VIIa相互作用以启动导致形成血液凝固酶复合物的复杂系列事件从而高效生成该酶时，这些事件便开始了。在这些过程中，凝血酶既有助于其最终生成所涉及的催化剂的产生，也有助于导致其生成减弱的催化剂的产生。凝血酶催化的事件既增强又减少凝血酶生成过程，该过程通过化学计量和动态抑制过程而下调。激活和抑制过程强度的组合为止血过程提供了严格的调节，建立了反应阈值，本质上导致了一个“开/关”开关。本综述简要总结了关于通过组织因子途径生成凝血酶及其调节的当今概念的知识演变。
