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. 2022 May 30;11(11):1789. doi: 10.3390/cells11111789

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Nutrient availability drives the dynamic cycle of protein O-GlcNAcylation via the hexosamine biosynthesis pathway. The GlcNAc provided by UDP-GlcNAc is necessary and unique for O-GlcNAcylation, and the only source of UDP-GlcNAc is HBP. Changes in nutritional availability, such as carbohydrates, lipids, amino acids, nucleotides and ATP, fluctuate HBP flux. Therefore, UDP-GlcNAc and HBP link carbohydrate metabolism, lipid metabolism, amino acid metabolism and nucleotide metabolism. These physiological characteristics make OGT extremely sensitive to nutrient fluctuations.