Edelberg J M, Weissler M, Pizzo S V
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
Biochem J. 1991 Jun 15;276 ( Pt 3)(Pt 3):785-91. doi: 10.1042/bj2760785.
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.
糖胺聚糖（GAGs）中的肝素、硫酸乙酰肝素和硫酸软骨素6-硫酸盐可刺激人纤溶酶原的尿激酶激活速率。纤溶酶原激活的动力学分析表明，肝素、硫酸乙酰肝素和硫酸软骨素6-硫酸盐分别使催化速率（Kcat）提高了5.3倍、3.5倍和2.5倍。这些具有刺激作用的GAGs对尿激酶与纤溶酶原的亲和力没有影响，因为反应的Km不受GAGs的改变。GAGs可能通过与尿激酶的催化结构域相互作用来提高纤溶酶原激活速率，解离常数约为30 nM。此外，脂蛋白、脂蛋白（a）[Lp（a）]和低密度脂蛋白（LDL）抑制肝素和硫酸乙酰肝素对纤溶酶形成的刺激作用。Lp（a）是一种竞争性抑制剂（抑制常数Kic为20 nM），LDL是肝素增强的尿激酶介导的纤溶酶原激活的混合型抑制剂（抑制常数Kic为24 nM，非竞争性抑制常数Kiu为60 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GAGs和脂蛋白可能在体内调节尿激酶介导的纤溶酶形成中发挥重要作用。
