Overview of the Hexosamine Biosynthetic Pathway (HBP) and O-GlcNAcylation. The HBP integrates four metabolism pathways, including carbohydrate (glucose), amino acid (glutamine), lipid (Acetyl-CoA) and nucleotide (UTP). Glucose becomes F-6P through the initial two steps shared by the HBP and glycolysis pathway. Only 2–3% F-6P enters the HBP, and in combination with glutamine, Acetyl-CoA and UTP generates UDP-GlcNAc. OGT catalyzes the transfer of GlcNAc moiety onto the serine (S) or threonine (T) site on the protein substrates, while OGA is able to remove the GlcNAc. Free GlcNAc can return to the HBP through the salvage pathway.