Fig. 1

A schematic overview of the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation. Glucose imported into the cells is rapidly converted to fructose-6-phosphate via the beginning stages of glycolysis. Then, under the catalysis of the rate-limiting enzyme GFAT and other enzymes, HBP integrates multiple metabolic nutrients, ultimately generating UDP-GlcNAc, which is a unique monosaccharide donor for O-GlcNAcylation. The O-GlcNAc cycling is a highly dynamic and reversible modification controlled by a pair of antagonistic enzymes, OGT and OGA. The metabolic and pharmacological interventions for studying the functional role of HBP/O-GlcNAcylation are illustrated with blue and green boxes, respectively