2022 review
Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars
[Review of ]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 322(6), C1201–C1213.
author keywords: hexosamine biosynthesis pathway; hyaluronan; nucleotide sugars; UDP-glucuronate; UDP-N-acetylglucosamine
MeSH headings : Glycosaminoglycans; Hyaluronan Synthases / genetics; Hyaluronic Acid / metabolism; Nucleotides; Sugars; Uridine Diphosphate N-Acetylglucosamine / metabolism
TL;DR:
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.
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UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
7. Affordable and Clean Energy
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Source: Web Of Science
Added: June 27, 2022
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.