Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina.
J Histochem Cytochem. 2021 Jan;69(1):13-23. doi: 10.1369/0022155420947500. Epub 2020 Aug 4.
Regulation of proteoglycan and glycosaminoglycan synthesis is critical throughout development, and to maintain normal adult functions in wound healing and the immune system, among others. It has become increasingly clear that these processes are also under tight metabolic control and that availability of carbohydrate and amino acid metabolite precursors has a role in the control of proteoglycan and glycosaminoglycan turnover. The enzyme uridine diphosphate (UDP)-glucose dehydrogenase (UGDH) produces UDP-glucuronate, an essential precursor for new glycosaminoglycan synthesis that is tightly controlled at multiple levels. Here, we review the cellular mechanisms that regulate UGDH expression, discuss the structural features of the enzyme, and use the structures to provide a context for recent studies that link post-translational modifications and allosteric modulators of UGDH to its function in downstream pathways.
蛋白聚糖和糖胺聚糖的合成调控在整个发育过程中至关重要，对于维持正常的成年功能，如创伤愈合和免疫系统等也很重要。越来越清楚的是，这些过程也受到严格的代谢控制，碳水化合物和氨基酸代谢物前体的可用性在蛋白聚糖和糖胺聚糖周转率的控制中起作用。酶尿苷二磷酸（UDP）-葡萄糖脱氢酶（UGDH）产生 UDP-葡萄糖醛酸，这是新糖胺聚糖合成的必需前体，其在多个水平受到严格控制。在这里，我们回顾了调节 UGDH 表达的细胞机制，讨论了该酶的结构特征，并利用这些结构为最近的研究提供了背景，这些研究将 UGDH 的翻译后修饰和别构调节剂与其在下游途径中的功能联系起来。
