Mizumoto Shuji, Yamada Shuhei
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Front Genet. 2021 Sep 3;12:717535. doi: 10.3389/fgene.2021.717535. eCollection 2021.
Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.
糖胺聚糖（GAGs），包括硫酸软骨素、硫酸皮肤素和硫酸乙酰肝素，与特定的核心蛋白共价连接形成蛋白聚糖，它们分布于细胞表面以及细胞外基质中。蛋白聚糖和GAGs已被证明具有多种生理功能，如细胞外基质的构建、组织发育以及通过与细胞外基质成分、形态发生素、细胞因子和生长因子相互作用进行细胞信号传导。不仅包括骨骼发育不良、软骨发育不良、多发性外生骨疣和埃勒斯-当洛综合征等结缔组织疾病，还有心脏和肾脏缺陷、免疫缺陷以及神经异常，都已被证明是由GAGs以及蛋白聚糖的核心蛋白缺陷引起的。这些发现表明，GAGs和蛋白聚糖对人体主要器官的发育至关重要。本文将基于迄今的文献，全面讨论由GAG生物合成酶（包括特定的糖基转移酶、表异构酶和硫酸转移酶）缺陷以及蛋白聚糖核心蛋白缺陷所导致的先天性疾病的糖生物学方面。
