This article addresses the role of platelet membrane phosphatidylserine (PS) in regulating the production of thrombin, the central regulatory molecule of blood coagulation. PS is normally located on the cytoplasmic face of the resting platelet membrane but appears on the plasma-oriented surface of discrete membrane vesicles that derive from activated platelets. Thrombin, the central molecule of coagulation, is produced from prothrombin by a complex ("prothrombinase") between factor Xa and its protein cofactor (factor V(a)) that forms on platelet-derived membranes. This complex enhances the rate of activation of prothrombin to thrombin by roughly 150,000 fold relative to factor X(a) in solution. It is widely accepted that the negatively charged surface of PS-containing platelet-derived membranes is at least partly responsible for this rate enhancement, although there is not universal agreement on mechanism by which this occurs. Our efforts have led to an alternative view, namely that PS molecules bind to discrete regulatory sites on both factors X(a) and V(a) and allosterically alter their proteolytic and cofactor activities. In this view, exposure of PS on the surface of activated platelet vesicles is a key regulatory event in blood coagulation, and PS serves as a second messenger in this regulatory process. This article reviews our knowledge of the prothrombinase reaction and summarizes recent evidence leading to this alternative viewpoint. This viewpoint suggests a key role for PS both in normal hemostasis and in thrombotic disease.

中文翻译：

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血小板膜磷脂酰丝氨酸的暴露可调节血液凝结。

本文探讨血小板膜磷脂酰丝氨酸（PS）在调节凝血酶（凝血的中央调节分子）产生中的作用。PS通常位于静止的血小板膜的细胞质面上，但出现在衍生自活化血小板的离散膜囊泡的血浆定向表面上。凝血酶是凝血的中心分子，是凝血酶Xa通过凝血因子Xa与在血小板衍生膜上形成的蛋白质辅因子（凝血因子V（a））之间的复合物（“凝血酶原”）产生的。相对于溶液中的因子X（a），该复合物将凝血酶原活化为凝血酶的速率提高了约150,000倍。尽管尚无关于发生这种机制的普遍共识，但人们普遍认为，含PS的血小板衍生膜带负电的表面至少部分负责这种速率的提高。我们的努力导致了另一种观点，即PS分子与X（a）和V（a）因子上的离散调控位点结合并变构地改变其蛋白水解和辅因子活性。根据这种观点，PS在活化血小板囊泡表面的暴露是凝血过程中的关键调节事件，而PS在此调节过程中充当第二信使。本文回顾了我们对凝血酶原反应的了解，并总结了导致这种替代观点的最新证据。这种观点表明PS在正常止血和血栓形成疾病中都起着关键作用。