Marciniak E
Br J Haematol. 1981 Jun;48(2):325-36.
Products obtained in reaction of excess antithrombin III (AT III) with human alpha-thrombin and heparin were found to contain markedly less of residual AT III than products of similar reactions without heparin. The increased utilization of AT III was primarily due to limited proteolysis of a portion of unbound inhibitor, associated with the release of a 50 000-dalton protein fragment. Thrombin-induced release of this fragment was promoted by polydispersed heparin preparation and, to a variable degree, by all heparin fractions obtained in gel filtration. The optimum amount of heparin required to facilitate AT III proteolysis was of 5 microgram/ml (0.8 u/ml). Excessive reduction of the residual inhibitory activity and changes in two-dimensional immunoelectrophoresis suggested that AT III in plasma is also subjected to nonproductive proteolysis and formation of a modified AT III derivative following addition of thrombin and heparin. These data indicate that the effect of heparin on AT III is more complex than generally recognized. On the one hand, heparin interacting with AT III and thrombin contributes to a rapid binding and neutralization of the enzyme; on the other, heparin facilitates proteolytic degradation of unbound inhibitor even in the presence of small quantities of thrombin accounting for excessive reduction of the overall inhibitory potential of AT III.
研究发现，过量抗凝血酶III（AT III）与人α-凝血酶及肝素反应所得到的产物中，残留的AT III明显少于无肝素参与的类似反应产物。AT III利用率的增加主要是由于一部分未结合抑制剂发生了有限的蛋白水解作用，并伴随着一个50000道尔顿蛋白质片段的释放。凝血酶诱导该片段的释放受到多分散肝素制剂的促进，并且在不同程度上受到凝胶过滤得到的所有肝素组分的促进。促进AT III蛋白水解所需的最佳肝素量为5微克/毫升（0.8单位/毫升）。残留抑制活性的过度降低以及二维免疫电泳的变化表明，血浆中的AT III在加入凝血酶和肝素后也会发生无活性的蛋白水解作用，并形成一种修饰的AT III衍生物。这些数据表明，肝素对AT III的作用比一般认为的更为复杂。一方面，肝素与AT III和凝血酶相互作用有助于酶的快速结合和中和；另一方面，即使存在少量导致AT III总体抑制潜能过度降低的凝血酶，肝素也会促进未结合抑制剂的蛋白水解降解。
