Kinetic analysis of various heparin fractions and heparin substitutes in the thrombin inhibition reaction.
Kinetic analysis of various heparin fractions and heparin substitutes in the thrombin inhibition reaction.
复制标题
凝血酶抑制反应中各种肝素组分和肝素替代品的动力学分析。
DOI：
10.1016/0304-4165(85)90256-9
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Nelsestuen,GL
中科院分区：
文献类型：
--
作者：
Pletcher,CH;Cunningham,M;Nelsestuen,GL
几种肝素制剂和替代肝素的动力学特性进行了测定，以帮助了解活性差异的基础。几种材料是高度活跃的Xa因子抑制和恒定的Xa因子浓度的反应速率出现预测的多糖诱导的内在抗凝血酶III荧光变化的程度。肝素馏分的不同分子量和亲和力的抗凝血酶III的凝血酶-抗凝血酶III反应的催化表现出类似的动力学参数时，这些参数表示的基础上的抗凝血酶III结合肝素。后者通过化学计量滴定肝素制剂引起的抗凝血酶III荧光变化来测定。然而，各种肝素馏分显示出非常不同的比活性每毫克总多糖。这表明功能性肝素分子具有相似的动力学性质，无论大小或抗凝血酶III结合亲和力如何，这是可能的，因为抗凝血酶III的Km由扩散而不是结合亲和力决定。替代肝素和解聚肝素是凝血酶抑制的不良催化剂，至少部分是由于它们对凝血酶的亲和力。后一种二元相互作用抑制肝素催化反应中的凝血酶反应。
Kinetic characteristics of several heparin preparations and substitute heparins were determined to help understand the bases for activity differences. Several materials were highly active in factor Xa inhibition and the reaction rate at constant factor Xa concentration appeared to be predicted by the extent of intrinsic antithrombin III fluorescence change induced by the polysaccharide. Heparin fractions of different molecular weight and affinity for antithrombin III showed similar kinetic parameters in catalysis of the thrombin-anti-thrombin III reaction when these parameters were expressed on the basis of antithrombin III-binding heparin. The latter was determined by stoichiometric titration of the antithrombin III fluorescence change by the heparin preparation. However, the various heparin fractions showed very different specific activities per mg of total polysaccharide. This indicated that functional heparin molecules had similar kinetic properties regardless of size or antithrombin III-binding affinity and is possible because theKmfor antithrombin III is determined by diffusion rather than by binding affinity. Substitute heparins and depolymerized heparin were poor catalysts for thrombin inhibition, due at least partially to their affinity for thrombin. This latter binary interaction inhibits thrombin reaction in the heparin-catalyzed reaction.