Kinetic analysis of the effects of glycosaminoglycans and lipoproteins on urokinase-mediated plasminogen activation.
Kinetic analysis of the effects of glycosaminoglycans and lipoproteins on urokinase-mediated plasminogen activation.
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糖胺聚糖和脂蛋白对尿激酶介导的纤溶酶原激活影响的动力学分析。
DOI：
10.1042/bj2760785
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Pizzo,SV
中科院分区：
文献类型：
--
作者：
Edelberg,JM;Weissler,M;Pizzo,SV
糖胺多聚糖(GAGS)肝素、硫酸肝素和6-硫酸软骨素可刺激人纤溶酶原尿激活率。对纤溶酶原激活的动力学分析表明，肝素、硫酸肝素和6-硫酸软骨素使纤溶酶原的催化速率(Kcat)分别提高了5.3、3.5和2.5倍。这些刺激性GAG不影响尿激酶对纤溶酶原的亲和力，因为反应的Km不被GAG改变。GAG可通过与尿激活酶的催化结构域相互作用来提高纤溶酶原激活的速率，其解离常数约为。30海里。此外，脂蛋白、脂蛋白(A)[Lp(A)]和低密度脂蛋白(LDL)可抑制肝素和硫酸肝素对纤溶酶形成的刺激。Lp(A)是竞争性抑制物(KIC20 NM)，低密度脂蛋白是肝素增强的尿激活型纤溶酶原激活的混合抑制物(KIC24 nM和KIU60 nM)。这些抑制常数与这些脂蛋白的生理浓度相关。这些数据表明，这些GAG和脂蛋白可能在体内调节尿激酶介导的纤溶酶的形成中发挥重要作用。
The glycosaminoglycans (GAGs) heparin, heparan sulphate and chondroitin 6-sulphate stimulate the rate of urokinase activation of human plasminogen. Kinetic analysis of plasminogen activation demonstrates that heparin, heparan sulphate and chondroitin 6-sulphate increased the catalytic rate (Kcat) by 5.3-, 3.5- and 2.5-fold respectively. These stimulatory GAGs had no effect on the affinity of urokinase for plasminogen, since the Km of the reaction is unaltered by the GAGs. The GAGs may enhance the rate of plasminogen activation through an interaction with the catalytic domain of the urokinase, with dissociation constants of approx. 30 nM. Additionally, the lipoproteins, lipoprotein (a) [Lp(a)] and low-density lipoprotein (LDL) inhibit heparin and heparan sulphate stimulation of plasmin formation. Lp(a) is a competitive inhibitor (Kic 20 nM) and LDL is a mixed inhibitor of heparin-enhanced urokinase-mediated plasminogen activation (Kic 24 nM and Kiu 60 nM). These inhibition constants correlate with physiological concentrations of these lipoproteins. These data suggest that these GAGs and lipoproteins may play an important role in vivo in regulating urokinase-mediated plasmin formation.