@misc{zimmer_barycki_simpson_2022, title={Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars}, volume={322}, ISSN={["1522-1563"]}, DOI={10.1152/ajpcell.00130.2022}, abstractNote={ Hyaluronan is a versatile macromolecule capable of an exceptional range of functions from cushioning and hydration to dynamic signaling in development and disease. Because of its critical roles, hyaluronan production is regulated at multiple levels including epigenetic, transcriptional, and posttranslational control of the three hyaluronan synthase (HAS) enzymes. Precursor availability can dictate the rate and amount of hyaluronan synthesized and shed by the cells producing it. However, the nucleotide-activated sugar substrates for hyaluronan synthesis by HAS also participate in exquisitely fine-tuned cross-talking pathways that intersect with glycosaminoglycan production and central carbohydrate metabolism. Multiple UDP-sugars have alternative metabolic fates and exhibit coordinated and reciprocal allosteric control of enzymes within their biosynthetic pathways to preserve appropriate precursor ratios for accurate partitioning among downstream products, while also sensing and maintaining energy homeostasis. Since the dysregulation of nucleotide sugar and hyaluronan synthesis is associated with multiple pathologies, these pathways offer opportunities for therapeutic intervention. Recent structures of several key rate-limiting enzymes in the UDP-sugar synthesis pathways have offered new insights to the overall regulation of hyaluronan production by precursor fate decisions. The details of UDP-sugar control and the structural basis for underlying mechanisms are discussed in this review. }, number={6}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY}, author={Zimmer, Brenna M. and Barycki, Joseph J. and Simpson, Melanie A.}, year={2022}, month={Jun}, pages={C1201–C1213} }
 @misc{zimmer_barycki_simpson_2021, title={Integration of Sugar Metabolism and Proteoglycan Synthesis by UDP-glucose Dehydrogenase}, volume={69}, ISSN={["1551-5044"]}, DOI={10.1369/0022155420947500}, abstractNote={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:}, number={1}, journal={JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY}, author={Zimmer, Brenna M. and Barycki, Joseph J. and Simpson, Melanie A.}, year={2021}, month={Jan}, pages={13–23} }