The factor VIII procofactor circulates as a metal ion-dependent heterodimer of a heavy chain and light chain. Activation of factor VIII results from limited proteolysis catalyzed by thrombin or factor Xa, which binds the factor VIII substrate over extended interactive surfaces. The proteases efficiently cleave factor VIII at three sites, two within the heavy and one within the light chain resulting in alteration of its covalent structure and conformation and yielding the active cofactor, factor VIIIa. The role of factor VIIIa is to markedly increase the catalytic efficiency of factor IXa in the activation of factor X. This effect is manifested in a dramatic increase in the catalytic rate constant, k(cat), by mechanisms that remain poorly understood.

中文翻译：

---

因子的激活和辅因子作用机制。

VIII因子前体因子作为重链和轻链的金属离子依赖性异二聚体循环。凝血酶或凝血因子Xa催化的有限蛋白水解作用导致凝血因子VIII活化，凝血酶或凝血因子Xa在扩展的相互作用表面上结合凝血因子VIII底物。蛋白酶在三个位点有效切割因子VIII，重链中两个，轻链中一个，导致其共价结构和构象的改变，并产生活性辅因子VIIIa。因子VIIIa的作用是显着增加因子IXa在激活因子X中的催化效率。这种作用表现为催化速率常数k（cat）的急剧增加，其机理尚不清楚。