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. Author manuscript; available in PMC: 2022 Apr 14.
Published in final edited form as: Curr Diabetes Rev. 2022;18(2):9–23. doi: 10.2174/1573399817999210111205933

Fig. (3). Glucose is metabolized by the hexosamine biosynthetic pathway to facilitate protein O-GlcNAcylation.

Fig. (3).

In addition to glucose, the synthesis of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) requires input from major metabolic pathways, including amino acid (blue), fatty acid (red), and nucleotide (green) metabolism. The first and rate-limiting step in this nutrient sensitive pathway involves the isomerization of fructose-6-phosphate to produce glucosamine-6-phosphate and is catalyzed by the enzyme glutamin-fructose-6-phosphate amidotransferase (GFAT). Alternatively, glucosamine enters the pathway downstream of this rate-limiting step. Protein O-GlcNAcylation involves the enzymatic O-linked addition of the GlcNAc moiety via the Ser/Thr hydroxyl side chain of a nucleocytoplasmic protein (shown as ribbon diagram) and is catalyzed by the enzyme O-GlcNAc transferase (OGT). The enzyme O-GlcNAcase (OGA) catalyzes the removal of the O-GlcNAc modification.