Advanced glycation end product (AGE) and hexosamine biosynthetic pathway (AGE (for advanced glycation end product), HBP (for hexosamine biosynthetic pathway))

Advanced glycation end products (AGEs) are a heterogeneous group of molecules formed via non-enzymatic reactions (Maillard reaction) between reducing sugars and protein, lipid, or nucleic acid amino groups, particularly under hyperglycemic and oxidative stress conditions as in diabetes. AGEs accumulate and contribute to cellular dysfunction by cross-linking proteins, promoting vascular stiffness, and activating intracellular signaling—primarily via the receptor for advanced glycation end products (RAGE)—to trigger inflammation and oxidative stress. The hexosamine biosynthetic pathway (HBP) is a metabolic route that diverts glucose to generate UDP-N-acetylglucosamine, thereby regulating O-GlcNAc modification of proteins and numerous aspects of cell signaling, influencing gene expression, and interacting with pathways such as PKC, polyol, and AGE formation. Both AGEs and hexosamine pathway intermediates are implicated in diabetes pathophysiology, driving inflammation, vascular damage, and metabolic memory even after normalization of glucose levels.

Other names

AGEs (advanced glycation end products)HBP (hexosamine biosynthetic pathway)glycoxidation end productsO-GlcNAc pathway

AGE inhibitors block formation of AGEs and/or disrupt AGE-RAGE interaction; Drugs modulating hexosamine pathway target enzymes or flux to alter protein glycosylation and signaling