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人肝脏糖原的分子结构

Molecular Structure of Human-Liver Glycogen.

作者信息

Deng Bin, Sullivan Mitchell A, Chen Cheng, Li Jialun, Powell Prudence O, Hu Zhenxia, Gilbert Robert G

机构信息

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.

Centre for Nutrition and Food Science, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, QLD, 4072, Australia.

出版信息

PLoS One. 2016 Mar 2;11(3):e0150540. doi: 10.1371/journal.pone.0150540. eCollection 2016.

Abstract

Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

摘要

糖原是一种高度分支的葡萄糖聚合物,参与维持血糖稳态。肝糖原包含由相连的β颗粒组成的大型复合α颗粒。先前的研究表明,在糖尿病小鼠中,将β颗粒连接成α颗粒的结合受到损害。本研究报告了来自非糖尿病患者的人肝糖原的首次分子结构特征,使用透射电子显微镜观察形态和尺寸排阻色谱分析分子大小分布;后者还作为体外酸水解过程中时间的函数进行研究,酸水解对某些结构特征敏感,特别是糖苷键与蛋白质键。将结果与在小鼠和猪中观察到的结果进行比较。每种情况下酸水解过程中的分子结构变化相似,表明β颗粒连接成α颗粒的键不是糖苷键。这一结果以及每种情况下相似的形态,共同表明人肝糖原与小鼠和猪的肝糖原具有相似的分子结构。这一知识将对未来糖尿病药物靶点有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a406/4775040/ff07abd27f5e/pone.0150540.g001.jpg

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