'Heparin' - from anticoagulant drug into the new biology
'Heparin' - from anticoagulant drug into the new biology
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DOI：
10.1023/a:1011030711317
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发表时间：
2000-06-01
影响因子：
3
通讯作者：
Lindahl, U
中科院分区：
文献类型：
--
作者：
Lindahl, U
本综述试图涵盖，从个人的角度来看，“肝素”领域的发展在过去的四十年。特别地，它强调了硫酸肝素（HS）的蜕变，从肝素生产中的一个令人不安的污染物到今天在细胞和发育生物学中的关键角色。我们对多糖的结构性质的了解已经大大促进了其生物合成的研究。我们现在对各种酶催化反应有了相当详细的了解，这些酶催化反应将初始的[4GlcA β 1- 4glcnac α 1-](n)聚合物转化为具有高度可变比例的GlcA/IdoA以及n -乙酰基、n -硫酸盐和o -硫酸盐取代基的硫酸酸化产物。人们还认识到，多糖的各种取代结构域以或多或少特定的方式与多种蛋白质相互作用，这些相互作用对蛋白质的生物学功能至关重要。分子遗传学已经揭示了合成肝素或HS链所需的几乎所有酶的基因结构，并表明其中一些蛋白质表现出遗传多态性。虽然酶同工型之间底物特异性的差异可能有助于解释特别是HS链的结构变异性，但我们仍然只部分了解肝素/HS生物合成及其调控的关键特征。
This overview attempts to cover, from a personal viewpoint, the development of the 'heparin' field during the last four decades. In particular, it emphasizes the metamorphosis of heparan sulfate (HS), from a disturbing contaminant in heparin production to the present-day key player in cell and developmental biology. Our understanding of the structural properties of the polysaccharides has been greatly promoted by studies of their biosynthesis. We now have a fairly detailed view of the various enzymatic reactions, that convert the initial [4GlcA beta1-4GlcNAc alpha1-](n) polymer into sulfated products with highly variable proportions of GlcA/IdoA and of N-acetyl, N-sulfate and O-sulfate substituents. It is also recognized that the variously substituted domains of the polysaccharide serve to interact, in more or less specific fashion, with a multitude of proteins, and that these interactions are essential to the biological functions of the proteins. Molecular genetics has unravelled the gene structures for almost all of the enzymes required to synthesize a heparin or HS chain, and has shown that several of these proteins exhibit genetic polymorphism. While differences in substrate specificity between enzyme isoforms may help to explain the structural variability of, in particular, HS chains, we still only partly understand the key features of heparin/HS biosynthesis and its regulation.