THROMBIN STRUCTURE AND FUNCTION - WHY THROMBIN IS THE PRIMARY TARGET FOR ANTITHROMBOTICS
THROMBIN STRUCTURE AND FUNCTION - WHY THROMBIN IS THE PRIMARY TARGET FOR ANTITHROMBOTICS
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DOI：
10.1097/00001721-199102000-00011
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发表时间：
1991-02-01
影响因子：
1.1
通讯作者：
MARAGANORE, JM
中科院分区：
文献类型：
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作者：
FENTON, JW;OFOSU, FA;MARAGANORE, JM
凝血酶既有有益作用，也有有害作用。按照重要性的顺序，在非常低的浓度下，α-凝血酶首先通过激活因子 V 和 VIII 来放大其自身的生成，因子 V 和 VIII 是抗血栓药物的主要靶标。其次，它在细胞水平上发挥作用，在低浓度下，它激活血小板，在较高浓度下，诱导内皮细胞变化（例如，形状变化、纤溶酶原激活剂和其他物质的白蛋白转运释放）。第三，它将纤维蛋白原转化为可凝结的纤维蛋白，并积极地融入形成的血栓中。此外，它还激活蛋白 C，从而降解因子 V 和 VIII（和/或其激活形式）并导致凝血酶生成停止。与凝血和纤溶系统的其他丝氨酸蛋白酶相比，α-凝血酶的独特之处在于它丢失了大部分酶原激活片段，并形成了多位点短程桥结合相互作用，这似乎可以解释凝血酶的特异性。了解凝血酶就是了解止血。
Thrombin has both beneficial and harmful effects. In order of importance, at very low concentrations, alpha-thrombin firstly amplifies its own generation through the activation of factors V and VIII, which are the primary targets of antithrombotic agents. It secondly functions at the cellular level where, at low concentrations it activates platelets, and at higher concentrations, induces endothelial cell changes (e.g., shape changes, albumin transport release of plasminogen activators and other substances). It thirdly converts fibrinogen into clottable fibrin and becomes actively incorporated into the forming thrombus. In addition, it activates protein C, which in turn degrades factors V and VIII (and/or their activated forms) and causes the shutdown of thrombin generation. When compared to other serine proteinases of the blood coagulation and fibrinolytic systems, alpha-thrombin is unique in that it loses most of its proenzyme activation fragment and has developed multisite short-ranged bridge-binding interactions, which appear to explain thrombin specificity. To understand thrombin is to understand haemostasis.