对抗凝血酶III无亲和力的硫酸乙酰肝素与止血控制

Heparan sulphate with no affinity for antithrombin III and the control of haemostasis.

作者信息

Scully M F, Ellis V, Kakkar V V

机构信息

Thrombosis Research Unit, King's College School of Medicine & Dentistry, London, England.

出版信息

FEBS Lett. 1988 Dec 5;241(1-2):11-4. doi: 10.1016/0014-5793(88)81020-2.

DOI:10.1016/0014-5793(88)81020-2

PMID:2973992

Abstract

Heparan sulphate with no affinity for antithrombin III (ATIII) was observed to cause acceleration of the factor Xa:ATIII interaction by 1100-fold (k2, 7 X 10(7) M-1.min-1) and the prothrombinase:ATIII interaction by 2900-fold (k2, 2.5 X 10(7) M-1.min-1). Although high-affinity heparan sulphate catalyzed higher acceleration and at lower concentration, in natural mixtures of the two forms the activity of the no affinity form predominated. Heparan sulphate had no significant effect on the thrombin:ATIII interaction but inhibited its potentiation by heparin (Kd 0.3 microM). From the estimated concentration of heparan sulphate on the endothelial cell surface it is proposed that the non-thrombogenic property of blood vessels is due to the acceleration of the factor Xa or prothrombinase:ATIII interaction by the greater mass of surface-bound heparan sulphate rather than by the much smaller proportion of heparin-like molecules (with high affinity for antithrombin III) which may be present.

摘要

观察到与抗凝血酶III（ATIII）无亲和力的硫酸乙酰肝素可使因子Xa与ATIII的相互作用加速1100倍（二级反应速率常数k2为7×10⁷ M⁻¹·min⁻¹），使凝血酶原酶与ATIII的相互作用加速2900倍（k2为2.5×10⁷ M⁻¹·min⁻¹）。尽管高亲和力的硫酸乙酰肝素在较低浓度下催化作用更强且加速作用更大，但在这两种形式的天然混合物中，无亲和力形式的活性占主导。硫酸乙酰肝素对凝血酶与ATIII的相互作用无显著影响，但可抑制肝素对其的增强作用（解离常数Kd为0.3微摩尔）。根据估计的内皮细胞表面硫酸乙酰肝素浓度，有人提出血管的非血栓形成特性是由于大量表面结合的硫酸乙酰肝素加速了因子Xa或凝血酶原酶与ATIII的相互作用，而不是由于可能存在的比例小得多的（与抗凝血酶III具有高亲和力的）类肝素分子。