THE MECHANISM OF POLYMERIZATION OF FIBRINOGEN

THE MECHANISM OF POLYMERIZATION OF FIBRINOGEN
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DOI:
10.1073/pnas.38.7.566
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发表时间:
1952-01-01
影响因子:
11.1
通讯作者:
FERRY, JD
FERRY, JD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
FERRY, JD

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介绍。-纤维蛋白原是一种长约600 A、分子量约350,000的棒状蛋白质,在凝血酶的催化作用下聚合形成纤维蛋白,即三维网状结构。在电子显微镜下观察到的网状链,通常在纤维蛋白原的几百倍长度上表现出均匀的宽度和很小的曲率;链的宽度可以是纤维蛋白原的两倍到多倍(约30 A),这取决于pH值和离子强度以及其他条件。有充分的证据表明纤维蛋白原单位在链内保持其同一性,并且它们的长轴在链方向上对齐。当凝血酶在异常低的pH值(约5)或异常高的离子强度下激活纤维蛋白原时,第一个(f)聚集;它具有与纤维蛋白原本身相同的总尺寸和形状,尽管它在激活过程中可能损失了一个或多个小片段;当恢复到正常的pH值和离子强度时,它迅速聚合。将纤维蛋白溶解在3.5 M尿素或2 M溴化锂或溴化钠中,也可以形成类似的分子。4当凝血酶在抑制剂如0.5 M丙二醇、50.5 M溴化锂或1 M尿素存在下激活纤维蛋白原时,第二中间体(fn)积累。[6]它似乎是f的部分聚合物,并用符号表示;通过改变溶剂组成,f可以转化为fn,反之亦然,fn在稀释时解离形成f。5 '7纤维蛋白原(F)向纤维蛋白的转化因此描绘如下:
Introduction.-Fibrinogen, a rod-like protein of length about 600 A and molecular weight about 350,000, polymerizes under the catalytic action of thrombin to form fibrin, a three-dimensional network structure. A network strand, as seen under the electron microscope, often exhibits uniform width and little curvatureover lengths many hundredtimes that of fibrinogen; the strand width may range from double to many times that of fibrinogen (about 30 A), depending on the pH and ionic strength and other conditions. There is good evidence that the fibrinogen units retain their identity within the strands and that their long axes are aligned in the strand direction.Two intermediates in the polymerization process have beenrecently identified. The first (f) accumulates when thrombin activates fibrinogen at abnormaUly low pH (about 5), 1 or at abnormally high ionic strength; it has the same gross size and shape as fibrinogen itself, though it has probably suffered the loss of one or more small fragments in the course of activation; 2 it polymerizesrapidly when returned to the normal pH and ionic strength. A similar molecule is formedby dissolving fibrin in 3.5 M urea3 or 2 M lithium or sodium bromide. 4 The second intermediate (fn) accumulateswhen thrombin activates fibrinogen in the presence of an inhibitor such as 0.5 M hexamethylene glycol, 50.5 M lithium bromide, or 1 M urea. 6 It appears to be a partial polymer of f and is so symbolized; f can be converted to fn and vice versa by changing the solvent composition;'and fn dissociates to form f simply upon dilution. 5'7 The conversion of fibrinogen (F) to fibrin is thus pictured as follows: