The conversion of prothrombin to thrombin. III. The factor Xa-catalyzed activation of prothrombin.
The conversion of prothrombin to thrombin. III. The factor Xa-catalyzed activation of prothrombin.
复制标题
凝血酶原转化为凝血酶。
DOI：
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发表时间：
1974
影响因子：
4.8
通讯作者：
C. Jackson
中科院分区：
文献类型：
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作者：
C. Esmon;C. Jackson
摘要 单独通过激活的因子 X 或通过激活的因子 X、因子 V、磷脂和钙离子激活凝血酶原，会导致蛋白酶凝血酶的形成，并且当用氟磷酸二异丙酯 (iPr2P-F) 阻止凝血酶蛋白水解时，会产生单个激活片段（片段 1.2）（Esmon, C. T.、Owen, W. G. 和 Jackson, C. M. (1974) 化学杂志 249, 606–611)。在提议解释这些和其他中间激活产物的两条途径中，本报告确定，仅通过因子 Xa 凝血酶原转化为凝血酶的主要（如果不是唯一的）途径是[方程式请参见 PDF] 如果允许发生凝血酶作用，则片段 1·2 被裂解成两种产物，片段 1 和片段 2，如 Esmon 等人所示。通过在不存在 iPr2P-F 的情况下直接测量中间体 2 和片段 1·2 的形成，证明了该特定途径并非以某种未知的方式依赖于 iPr2P-F 的存在。这些实验是通过激活氚标记的凝血酶原并在可以独立评估凝血酶作用的条件下确定十二烷基硫酸钠电泳凝胶中的产物分布来进行的。中间体 2 位于从凝血酶原到凝血酶的直接途径上的必要要求，即中间体 2 的活化速率大于或等于凝血酶原活化的速率，已被证明得到满足。还尝试证明可解释片段 1·2（尽管不是中间体 2）的替代途径的存在，但没有发现其存在或对因子 Xa 催化的激活过程的贡献的证据。
Abstract Prothrombin activation either by activated Factor X alone or by activated Factor X, Factor V, Phospholipid, and calcium ions results in the formation of the protease thrombin and, when thrombin proteolysis is prevented with diisopropyl fluorophosphate (iPr2P-F), a single activation fragment (Fragment 1.2) (Esmon, C. T., Owen, W. G., and Jackson, C. M. (1974) J. Biol. Chem. 249, 606–611). Of the two pathways which were proposed to account for these and other intermediate activation products, it is established by this report that the principal, if not exclusive, route of prothrombin conversion to thrombin by Factor Xa alone is [see PDF for equation] If thrombin action is permitted to occur, Fragment 1·2 is cleaved into two products, Fragment 1 and Fragment 2 as shown by Esmon et al. That this particular pathway is not in some unknown way dependent upon the presence of iPr2P-F was demonstrated by measuring the formation of Intermediate 2 and Fragment 1·2 directly in the absence of iPr2P-F. These experiments were carried out by activating tritium-labeled prothrombin and determining the product distributions in sodium dodecyl sulfate electrophoresis gels under conditions in which thrombin action could be independently assessed. The necessary requirement for Intermediate 2 being on the direct pathway from prothrombin to thrombin, i.e. that the rate of Intermediate 2 activation be greater than or equal to that of prothrombin activation, was shown to be met. An attempt to demonstrate the existence of the alternative pathway which can account for Fragment 1·2, although not Intermediate 2, was also made but no evidence for its existence or contribution to the Factor Xa-catalyzed activation process was found.