多种血浆蛋白酶抑制剂对人凝血因子Xa的抑制作用

Inhibition of human factor Xa by various plasma protease inhibitors.

作者信息

Ellis V, Scully M, MacGregor I, Kakkar V

出版信息

Biochim Biophys Acta. 1982 Feb 4;701(1):24-31.

Abstract

The inhibitory effects of the plasma protease inhibitors antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin on the activity of human factor Xa have been studied using purified proteins. The rate of inhibition was determined by measuring the residual factor Xa activity at timed intervals utilizing the synthetic peptide susbtrate Bz-Ile-Glu(piperidyl)-Gly-Arg-pNA. Kinetic analysis with varying molar concentrations of inhibitors demonstrated that the inhibition of factor Xa by antithromin III, alpha 2-macroglobulin and alpha 1-antitrypsin followed second-order kinetics. Calculated values of the rate constants for the inhibition of factor Xa by antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin were 5.8 . 10(4), 4.00 . 10(4) and 1.36 . 10(4) M -1 . min -1, respectively. The plasma concentrations of the inhibitors can be used to assess their potential relative effectiveness against factor Xa. In plasma this was found as alpha 1-antitrypsin greater than antithrombin III greater than alpha 2-macroglobulin in the ratio 4.64: 2.08: 1.0. Cephalin was shown to inhibit the rate of reaction between factor Xa and antithrombin III.

摘要

利用纯化蛋白研究了血浆蛋白酶抑制剂抗凝血酶III、α2-巨球蛋白和α1-抗胰蛋白酶对人凝血因子Xa活性的抑制作用。通过使用合成肽底物Bz-Ile-Glu（哌啶基）-Gly-Arg-pNA在设定时间间隔测量残余凝血因子Xa活性来确定抑制率。用不同摩尔浓度的抑制剂进行动力学分析表明，抗凝血酶III、α2-巨球蛋白和α1-抗胰蛋白酶对凝血因子Xa的抑制遵循二级动力学。抗凝血酶III、α2-巨球蛋白和α1-抗胰蛋白酶抑制凝血因子Xa的速率常数计算值分别为5.8×10⁴、4.00×10⁴和1.36×10⁴M⁻¹·min⁻¹。抑制剂的血浆浓度可用于评估它们对凝血因子Xa的潜在相对有效性。在血浆中，发现α1-抗胰蛋白酶、抗凝血酶III、α2-巨球蛋白的比例为4.64:2.08:1.0。已证明脑磷脂可抑制凝血因子Xa与抗凝血酶III之间的反应速率。