Castellino F J, Urano T, de Serrano V, Morris J P, Chibber B A
Department of Chemistry, University of Notre Dame, Indiana 46556.
Haemostasis. 1988;18 Suppl 1:15-23. doi: 10.1159/000215833.
The activation of Glu1-plasminogen (Glu-Pg) by streptokinase (SK), urokinase (UK) and tissue plasminogen activator (tPA) is under rigorous control by molecules such as epsilon-aminocaproic acid (EACA), fibrinogen (Fg), fibrin (Fn) and, as we have recently discovered, anions. This presentation will focus on the biochemical mechanisms that are involved in these processes. In the case of activation by SK, a species of activator complex, composed of Glu-Pg and SK, can be identified that is inhibited by anions, such as Cl-, and stimulated by Fg and Fn. This species rapidly decays to another activator complex, also consisting of Glu-Pg and SK, that is much less sensitive to control by these effector molecules. The most stable activator complex, containing equimolar SK and plasmin, is not affected to a great extent by anions, Fg or Fn. In the overall activation of Glu-Pg by SK, Cl- behaves as a mixed inhibitor, with a Ki of 6.4-9.2 mM, and Fg functions as a mixed activator, displaying a Ka of 110-240 nM. These results show that activation of Glu-Pg by SK in physiological samples would be considerably inhibited by Cl- in the absence of Fg. The activation of Glu-Pg by both high- and low-molecular weight UK is also inhibited by Cl-, but is stimulated by EACA. The inhibition by Cl- does not occur in the presence of concentrations of EACA that saturate its weak binding sites on Glu-Pg, and the stimulation by EACA is maximally exhibited in the presence of Cl-.(ABSTRACT TRUNCATED AT 250 WORDS)
链激酶（SK）、尿激酶（UK）和组织型纤溶酶原激活剂（tPA）对Glu1-纤溶酶原（Glu-Pg）的激活受到ε-氨基己酸（EACA）、纤维蛋白原（Fg）、纤维蛋白（Fn）以及我们最近发现的阴离子等分子的严格调控。本报告将聚焦于这些过程中涉及的生化机制。在SK激活的情况下，可以鉴定出一种由Glu-Pg和SK组成的激活剂复合物，它会受到Cl-等阴离子的抑制，并被Fg和Fn刺激。该复合物会迅速衰变为另一种同样由Glu-Pg和SK组成的激活剂复合物，而后者对这些效应分子的调控不太敏感。最稳定的激活剂复合物，含有等摩尔的SK和纤溶酶，在很大程度上不受阴离子、Fg或Fn的影响。在SK对Glu-Pg的整体激活过程中，Cl-表现为混合抑制剂，Ki为6.4 - 9.2 mM，Fg则作为混合激活剂，Ka为110 - 240 nM。这些结果表明，在生理样本中，若没有Fg，Cl-会显著抑制SK对Glu-Pg的激活。高分子量和低分子量UK对Glu-Pg的激活也受到Cl-的抑制，但会被EACA刺激。当EACA的浓度饱和其在Glu-Pg上的弱结合位点时，Cl-的抑制作用不会发生，且EACA的刺激作用在有Cl-存在时表现得最为明显。（摘要截短至250字）
