Figure 5.The hexosamine biosynthesis pathway (HBP) splits from the glycolytic pathway with the reaction of fructose-6-phosphate (F6P) with the NH2 donor amino acid, glutamine, being converted to glucosamine-6-phosphate (GlcN6P) by the rate-limiting enzyme, glutamine fructose-6-phosphate amidotransferase (GFA). Subsequent reactions result in the formation of UDP-GlcNAc (uridine diphosphate N-acteylglucosamine) which is utilized as a substrate for N- and O-linked glycosylation. It is intracellular protein O-glycosylation mediated by OGT (O-linked GlcNAc transferase) which has been postulated to contribute to glucose toxicity by altering gene expression. Many studies use glucosamine as an agent to drive this pathway to investigate the consequences of increased flux through the HBP. Glucosamine bypasses the rate limiting GFA.