Schatteman K A, Goossens F J, Scharpé S S, Hendriks D F
From the Department of Clinical Biochemistry, University of Antwerp, Universiteitsplein 1, B-2610, Wilrijk, Belgium.
Clin Chim Acta. 2000 Feb 25;292(1-2):25-40. doi: 10.1016/s0009-8981(99)00205-3.
Carboxypeptidase U (CPU, EC 3.4.17.20) is a recently described basic carboxypeptidase which circulates in plasma as an enzymatically inactive precursor procarboxypeptidase U (proCPU), also known as plasma carboxypeptidase B precursor or thrombin activatable fibrinolysis inhibitor (TAFI). The activation of the zymogen proceeds through a proteolytic cleavage at Arg-92. The active form - CPU - is able to retard the initial phase of fibrinolysis by cleaving C-terminal lysine residues exposed on fibrin partially degraded by the action of plasmin. These C-terminal lysine residues are essential for the high affinity binding of plasminogen to fibrin and the subsequent activation to plasmin. In this report, the activation of purified human proCPU was studied using trypsin and some key proteases of the coagulation and fibrinolytic cascade, i.e., kallikrein, plasmin and thrombin. The most efficient activation is obtained in the presence of thrombin in complex with thrombomodulin. After in vitro activation, CPU is unstable at 37 degrees C (T(1/2)=15 min). Its stability can be improved dramatically using lower temperatures.
羧肽酶U（CPU，EC 3.4.17.20）是一种最近被描述的碱性羧肽酶，它以无酶活性的前体羧肽酶U（proCPU）的形式在血浆中循环，proCPU也被称为血浆羧肽酶B前体或凝血酶激活的纤维蛋白溶解抑制剂（TAFI）。酶原的激活通过在精氨酸92处的蛋白水解切割进行。活性形式——CPU——能够通过切割纤溶酶作用后暴露在部分降解的纤维蛋白上的C末端赖氨酸残基来延缓纤维蛋白溶解的初始阶段。这些C末端赖氨酸残基对于纤溶酶原与纤维蛋白的高亲和力结合以及随后激活为纤溶酶至关重要。在本报告中，使用胰蛋白酶以及凝血和纤维蛋白溶解级联反应的一些关键蛋白酶，即激肽释放酶、纤溶酶和凝血酶，研究了纯化的人proCPU的激活。在凝血酶与血栓调节蛋白形成复合物的情况下可获得最有效的激活。体外激活后，CPU在37℃时不稳定（半衰期T(1/2)=15分钟）。使用较低温度可显著提高其稳定性。
