Zhang Xu, Wang Fengshan, Sheng Juzheng
Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; National Glycoengineering Research Center, Shandong University, Jinan 250012, China.
Carbohydr Res. 2016 Jun 16;428:1-7. doi: 10.1016/j.carres.2016.04.002. Epub 2016 Apr 8.
Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity.
硫酸乙酰肝素（HS）以HS蛋白聚糖的形式广泛分布于哺乳动物组织中，在各种生理和病理过程中发挥着重要作用。与DNA和蛋白质合成中涉及的模板导向过程不同，HS生物合成被认为不涉及模板。然而，HS链的最终结构似乎受到严格调控。在此，我们报告基于研究的假说，即HS生物合成涉及两个主要步骤，即“编码”和“解码”步骤，这两个步骤严格调控其化学结构和生物活性。在此背景下，“编码”过程基于HS链中葡萄糖胺残基氨基上硫酸基团的分布。这些胺基的硫酸化由具有四种同工酶的N-脱乙酰酶/N-磺基转移酶催化。HS聚糖链上硫酸基团和艾杜糖醛酸残基的组成和分布由其他几种修饰酶决定，这些酶可以识别这些编码序列（即“解码”过程）。HS链中硫酸化和差向异构化的程度和模式决定了它们与几种不同蛋白质因子相互作用的程度，这进一步影响它们的生物活性。
