Lindahl U
Inst för medicinsk och fysiologisk kemi, Uppsala Universitet, Biomedicum.
Nord Med. 1994;109(1):4-8.
The polysaccharide heparin, produced by mast cells, had been used in the prophylaxis and treatment of thrombotic disease long before the molecular mechanism responsible for its anticoagulant activity was elucidated. The anticoagulant effect is particularly dependent upon the presence of a specific pentasaccharide sequence, which binds to the proteinase inhibitor, antithrombin. Detailed knowledge of this mechanism enabled the development of low-molecular weight heparin with improved therapeutic properties. Studies on the biosynthesis of heparin have revealed the essential features of the generation of such complex saccharide sequences, the initial formation of a simple, repetitive polymer is followed by the action of a number of modifying enzymes. Though the mode of regulation of these enzymes is still only partly understood, heparan sulphate, structurally related to heparin, has been found to be generated by virtually all the mammalian cells studied, and is typically exposed as a proteoglycan at cell surfaces. Recent findings suggest specific heparan sulphate sequences to be crucially involved in the action of certain growth factors.
肥大细胞产生的多糖类物质肝素，早在其抗凝活性的分子机制被阐明之前，就已用于血栓性疾病的预防和治疗。抗凝作用尤其依赖于特定的五糖序列的存在，该序列可与蛋白酶抑制剂抗凝血酶结合。对这一机制的详细了解促使了具有更好治疗特性的低分子量肝素的研发。肝素生物合成的研究揭示了这类复杂糖序列产生的基本特征，即先形成简单的重复聚合物，随后由多种修饰酶发挥作用。尽管这些酶的调节方式仍仅部分为人所知，但已发现硫酸乙酰肝素在结构上与肝素相关，几乎在所有研究的哺乳动物细胞中都能产生，并且通常以蛋白聚糖的形式暴露于细胞表面。最近的研究结果表明，特定的硫酸乙酰肝素序列在某些生长因子的作用中起着关键作用。
