Holmer E, Söderström G, Andersson L O
Eur J Biochem. 1979 Jan 2;93(1):1-5. doi: 10.1111/j.1432-1033.1979.tb12787.x.
The rate of the reaction between thrombin and antithrombin III is greatly increased in the presence of heparin. Several mechanisms for this effect are possible. To study the problems commercial heparin was fractionated into one fraction of high anticogulant activity and one of low anticoagulant activity by affinity chromatography on matrix-bound antithrombin III. The strength of the binding of the two heparin fractions to antithrombin III and thrombin, respectively, was determined by a crossed immunoelectrophoresis technique. As was to be expected, the high activity fraction was strongly bound to antithrombin III while the low activity fraction was weakly bound. In contrast, thrombin showed equal binding affinity for both heparin fractions. The ability of the two heparin fractions to catalyse the inhibition of thrombin by antithrombin III was determined and was found to be much greater for the high activity heparin fraction. A mechanism for the reaction between thrombin and antithrombin III in the presence of small amounts of heparin is suggested, whereby antithrombin III first binds heparin and this complex then inhibits thrombin by interaction with both the bound heparin and the antithrombin III.
在肝素存在的情况下，凝血酶与抗凝血酶III之间的反应速率会大幅提高。这种效应可能有几种机制。为了研究这些问题，通过在与抗凝血酶III结合的基质上进行亲和色谱，将商业肝素分离成一种高抗凝活性组分和一种低抗凝活性组分。采用交叉免疫电泳技术分别测定了这两种肝素组分与抗凝血酶III和凝血酶的结合强度。正如所预期的，高活性组分与抗凝血酶III紧密结合，而低活性组分则结合较弱。相反，凝血酶对两种肝素组分表现出相同的结合亲和力。测定了这两种肝素组分催化抗凝血酶III抑制凝血酶的能力，发现高活性肝素组分的这种能力要强得多。提出了在少量肝素存在下凝血酶与抗凝血酶III之间反应的一种机制，即抗凝血酶III首先结合肝素，然后该复合物通过与结合的肝素和抗凝血酶III相互作用来抑制凝血酶。
