Fig. 1

Schematic illustration of Hexosamine biosynthetic pathway and protein O-GlcNAcylation. Glucose-6-phosphate isomerase converts glucose to fructose-6-phosphate. Both fructose-6-phosphate and glucose-6-phosphate can be metabolized through glycolysis or the hexosamine biosynthetic pathway (HBP). The rate-limiting enzyme of the HBP, known as GFPT1 or GFAT, catalyzes the conversion of fructose-6-phosphate to glucosamine-6-phosphate using glutamine as the amide donor. The expression of GFAT mRNA and protein is upregulated by saturated fatty acids, while feedback inhibition occurs due to its enzymatic product, glucosamine-6-phosphate. Subsequently, the enzyme GNA1 converts acetyl-CoA and glucosamine-6-phosphate to CoA and N-acetylglucosamine-6-phosphate. Another enzyme, PGM3, converts N-acetylglucosamine-6-phosphate to N-acetylglucosamine-1-phosphate, with glucose-1,6-bisphosphate serving as a co-factor. Finally, UDP-N-acetylglucosamine is synthesized by adding UTP to N-acetylglucosamine through the action of UAP1