The activation of prothrombin. I. Isolation and preliminary characterization of intermediates.
The activation of prothrombin. I. Isolation and preliminary characterization of intermediates.
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凝血酶原的激活。
DOI：
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发表时间：
1973
影响因子：
4.8
通讯作者：
K. Mann
中科院分区：
文献类型：
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作者：
C. Heldebrant;K. Mann
摘要对凝血酶原在25%柠檬酸钠溶液中活化过程中形成的中间体进行了分离和部分表征。它们的性质与先前提出的25%柠檬酸钠中凝血酶原激活模型预测的一致：（72，000道尔顿）→中间体1（65，000道尔顿）→中间体2（39，000道尔顿）和中间体3（25，000道尔顿）;中间体2（39，000道尔顿）→凝血酶（α-凝血酶，39，000道尔顿）（Mann，K. G.，海尔德布兰特角M.，和Fass，D. N.（1971）J.BiolChem.246，6106-6114）。如所预测的，中间体1和2可以被活化为凝血酶，而中间体3不能。中间体2的色谱行为与凝血酶的色谱行为几乎相同。分子量和氨基酸组成数据强烈表明，α-凝血酶是通过中间体2序列的少量损失（如果有的话）由中间体2形成的。显示中间体2和3是凝血酶原序列的基本上独立的部分。衍生自中间体2和3的胰蛋白酶肽虽然非常不同，但占衍生自凝血酶原的胰蛋白酶肽的85%以上。此外，中间体3含有几乎两倍于中间体2的半胱氨酸和超过两倍于中间体2的中性糖。凝血酶原活化产物（显然源自中间体3）已显示可改变凝血酶对N-α-甲苯磺酰基-L-精氨酸甲酯和纤维蛋白原的活性。凝血酶的特异性改变的可能性，可能参与控制和调节凝血进行了讨论。
Abstract The intermediates formed during the activation of prothrombin in 25% sodium citrate solutions have been isolated and partially characterized. Their properties are in agreement with those predicted by a previously proposed model for prothrombin activation in 25% sodium citrate: prothrombin (72,000 daltons) → intermediate 1 (65,000 daltons) → Intermediate 2 (39,000 daltons) and Intermediate 3 (25,000 daltons); Intermediate 2 (39,000 daltons) → thrombin (α-thrombin, 39,000 daltons) (Mann, K. G., Heldebrant, C. M., and Fass, D. N. (1971) J. Biol Chem. 246, 6106–6114). Intermediates 1 and 2, as predicted, can be activated to thrombin, while Intermediate 3 cannot. The chromatographic behavior of Intermediate 2 is nearly identical with that of thrombin. Molecular weight and amino acid composition data strongly suggest that α-thrombin is formed from Intermediate 2 by the loss of little, if any, of the Intermediate 2 sequence. Intermediates 2 and 3 are shown to be substantially independent portions of the prothrombin sequence. The tryptic peptides derived from Intermediates 2 and 3, while very dissimilar account for greater than 85% of the tryptic peptides derived from prothrombin. Furthermore, Intermediate 3 contains nearly twice as much half-cystine and more than twice as much neutral sugar as Intermediate 2. A product of prothrombin activation, apparently derived from Intermediate 3, has been shown to alter the activity of thrombin toward N-α-tosyl-l-arginine methyl ester and fibrinogen. The possibility that a thrombin of altered specificity may participate in the control and regulation of coagulation is discussed.