Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia.
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia.
Am J Physiol Cell Physiol. 2022 May 1;322(5):C849-C864. doi: 10.1152/ajpcell.00085.2022. Epub 2022 Mar 16.
Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates play important roles in many cellular processes and have been implicated in many disease states, including cancer, inflammation, and genetic disorders. GAGs are among the most complex molecules in biology with enormous information content and extensive structural and functional heterogeneity. GAG biosynthesis is a nontemplate-driven process facilitated by a large group of biosynthetic enzymes that have been extensively characterized over the past few decades. Interestingly, the expression of the enzymes and the consequent structure and function of the polysaccharide chains can vary temporally and spatially during development and under certain pathophysiological conditions, suggesting their assembly is tightly regulated in cells. Due to their many key roles in cell homeostasis and disease, there is much interest in targeting the assembly and function of GAGs as a therapeutic approach. Recent advances in genomics and GAG analytical techniques have pushed the field and generated new perspectives on the regulation of mammalian glycosylation. This review highlights the spatiotemporal diversity of GAGs and the mechanisms guiding their assembly and function in human biology and disease.
糖胺聚糖（GAGs）是长链线性多糖，广泛表达于所有动物细胞的细胞表面和细胞外基质中。这些复杂的碳水化合物在许多细胞过程中发挥着重要作用，并与许多疾病状态有关，包括癌症、炎症和遗传疾病。GAGs 是生物学中最复杂的分子之一，具有巨大的信息含量和广泛的结构与功能异质性。GAG 的生物合成是一个非模板驱动的过程，由一大组生物合成酶来促进，这些酶在过去几十年中得到了广泛的研究。有趣的是，这些酶的表达以及多糖链的结构和功能会在发育过程中以及在某些病理生理条件下随时间和空间而变化，这表明它们的组装在细胞中受到严格调控。由于 GAGs 在细胞稳态和疾病中的许多关键作用，人们对靶向 GAG 组装和功能作为一种治疗方法产生了浓厚的兴趣。基因组学和 GAG 分析技术的最新进展推动了该领域的发展，并为哺乳动物糖基化的调控提供了新的视角。本综述强调了 GAG 的时空多样性，以及指导其在人类生物学和疾病中组装和功能的机制。
