Schoen P, Lindhout T
J Biol Chem. 1987 Aug 15;262(23):11268-74.
The inhibition of thrombin by antithrombin III (AT III) and heparin has been studied in pure systems to determine the kinetics of inhibition during human prothrombin activation. The present study shows that prothrombinase-catalyzed prothrombin activation resulted in the generation of thrombin and meizothrombin(des F1). In the absence of heparin the second-order rate constants of the inactivation of both thrombin and meizothrombin(des F1) formed in the reaction mixture appeared to be identical, k = 3.7 X 10(5) M-1 min-1. The rate constant of inhibition of purified thrombin was 6.5 X 10(5) M-1 min-1. In the presence of heparin the decay of the amidolytic activity was biexponential and could be modeled by a four-parameter equation to determine the pseudo first-order rate constants of inhibition as well as the composition of the reaction with respect to the levels of thrombin and meizothrombin(des F1). The ratio of thrombin over meizothrombin(des F1) varied with the initial prothrombin concentration. Heparin catalyzed the AT III inhibition of thrombin but not meizothrombin(des F1) formed during the prothrombin activation. Thrombin, generated by (Xa-Va-phospholipid-Ca2+) was inhibited by AT III/heparin more slowly than purified thrombin, and the saturation kinetics of the inhibition with respect to AT III differed from those found with purified thrombin.
在纯体系中研究了抗凝血酶III（AT III）和肝素对凝血酶的抑制作用，以确定人凝血酶原激活过程中的抑制动力学。本研究表明，凝血酶原酶催化的凝血酶原激活导致凝血酶和中凝血酶（去F1）的生成。在没有肝素的情况下，反应混合物中形成的凝血酶和中凝血酶（去F1）失活的二级速率常数似乎相同，k = 3.7×10⁵ M⁻¹ min⁻¹。纯化凝血酶的抑制速率常数为6.5×10⁵ M⁻¹ min⁻¹。在有肝素的情况下，酰胺水解活性的衰减是双指数的，可以用四参数方程建模，以确定抑制的伪一级速率常数以及反应相对于凝血酶和中凝血酶（去F1）水平的组成。凝血酶与中凝血酶（去F1）的比例随凝血酶原初始浓度而变化。肝素催化AT III对凝血酶的抑制作用，但不催化对凝血酶原激活过程中形成的中凝血酶（去F1）的抑制作用。由（Xa-Va-磷脂-Ca²⁺）产生的凝血酶被AT III/肝素抑制的速度比纯化凝血酶慢，并且相对于AT III的抑制饱和动力学与纯化凝血酶不同。
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