小柯机器人

美国肯塔基大学Matthew S. Gentry、Ramon C. Sun等研究人员合作发现，脑糖原可作为蛋白质糖基化所需的关键氨基葡萄糖贮藏库。相关论文于2021年5月26日在线发表在《细胞—代谢》杂志上。

研究人员发现，大脑中的N-连接蛋白糖基化通过糖原分解代谢途径传导至葡萄糖胺代谢。结果表明，氨基葡萄糖是脑糖原的丰富组成部分，它可以作为多种糖结合物的氨基葡萄糖储存库。研究人员证明了糖原合酶将葡糖胺以酶促方式掺入糖原中，并通过生化和结构方法通过糖原磷酸化酶在原代星形胶质细胞中释放，而且通过同位素示踪和质谱在体内进行了释放。

使用糖原贮积病的两种小鼠模型，研究人员表明脑糖原代谢的破坏会导致UDP-N-乙酰氨基葡萄糖和N-连接蛋白质糖基化池的整体减少。这些发现揭示了脑糖原在蛋白质糖基化中的基本生物学作用，并与中枢神经系统的多种人类疾病直接相关。

据悉，糖基化缺陷是许多神经系统疾病的标志。但是，这种病理的分子和代谢基础尚未完全了解。

附：英文原文

Title: Brain glycogen serves as a critical glucosamine cache required for protein glycosylation

Author: Ramon C. Sun, Lyndsay E.A. Young, Ronald C. Bruntz, Kia H. Markussen, Zhengqiu Zhou, Lindsey R. Conroy, Tara R. Hawkinson, Harrison A. Clarke, Alexandra E. Stanback, Jessica K.A. Macedo, Shane Emanuelle, M. Kathryn Brewer, Alberto L. Rondon, Annette Mestas, William C. Sanders, Krishna K. Mahalingan, Buyun Tang, Vimbai M. Chikwana, Dyann M. Segvich, Christopher J. Contreras, Elizabeth J. Allenger, Christine F. Brainson, Lance A. Johnson, Richard E. Taylor, Dustin D. Armstrong, Robert Shaffer, Charles J. Waechter, Craig W. Vander Kooi, Anna A. DePaoli-Roach, Peter J. Roach, Thomas D. Hurley, Richard R. Drake, Matthew S. Gentry

Issue&Volume: 2021-05-26

Abstract: Glycosylation defects are a hallmark of many nervous system diseases. However, themolecular and metabolic basis for this pathology is not fully understood. In thisstudy, we found that N-linked protein glycosylation in the brain is metabolicallychanneled to glucosamine metabolism through glycogenolysis. We discovered that glucosamineis an abundant constituent of brain glycogen, which functions as a glucosamine reservoirfor multiple glycoconjugates. We demonstrated the enzymatic incorporation of glucosamineinto glycogen by glycogen synthase, and the release by glycogen phosphorylase by biochemicaland structural methodologies, in primary astrocytes, and in vivo by isotopic tracing and mass spectrometry. Using two mouse models of glycogen storagediseases, we showed that disruption of brain glycogen metabolism causes global decreasesin free pools of UDP-N-acetylglucosamine and N-linked protein glycosylation. Thesefindings revealed fundamental biological roles of brain glycogen in protein glycosylationwith direct relevance to multiple human diseases of the central nervous system.

DOI: 10.1016/j.cmet.2021.05.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00220-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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