Hexosamine biosynthetic pathway (HBP)

The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing and glycosylation-driving metabolic pathway that diverts a small fraction of glucose and other nutrients (glutamine, acetyl-CoA, UTP) toward the synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc), a critical substrate for both N- and O-glycosylation of proteins and lipids. The pathway is primarily regulated by the rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase (GFAT). HBP activity is responsive to metabolic state and has been implicated in the regulation of cell signaling, protein quality control, and the pathogenesis of cancer, diabetes, immunological, and degenerative diseases. While not a molecular target itself, the pathway is therapeutically exploited by targeting its key enzymes

Other names

Glucosamine pathwayHexosamine pathwayHBP

Inhibition of rate-limiting enzymes (e.g., GFAT) to reduce UDP-GlcNAc production; Inhibition of O-GlcNAc transferase (OGT) to modulate O-GlcNAcylation; Inhibition of O-GlcNAcase (OGA) to increase O-GlcNAcylation; Supplementation (glucosamine/GlcNAc) to increase end product UDP-GlcNAc