Glycosaminoglycan metabolism

Glycosaminoglycans (GAGs) are long, unbranched polysaccharides containing a repeating disaccharide unit composed of a hexosamine (either N-acetylgalactosamine (GalNAc) or N-acetylglucosamine (GlcNAc)) and a uronic acid (glucuronate or iduronate). They can be heavily sulfated. All GAGs (except hyaluronan) are bound to proteoglycans (PG) via the tetrasaccharide linker -GlcA-Gal-Gal-Xyl- on O-serine residues of the core protein. Hyaluronan and GAG-PGs are located primarily in the extracellular matrix (ECM) and on cell membranes, acting as a lubricating fluid for joints and as part of signalling processes. They have structural roles in connective tissue, cartilage, bone and blood vessels. GAG-PGs are degraded in the lysosome as part of their natural turnover. Defects in the lysosomal enzymes responsible for the metabolism of membrane-associated GAG-PGs lead to lysosomal storage diseases called mucopolysaccharidoses (MPS). MPSs are characterised by the accumulation of GAGs in lysosomes resulting in chronic, progressively debilitating disorders that in many instances lead to severe psychomotor retardation and premature death.It is unclear but probable that GAG chains are cleaved off PGs, leaving the tetrasaccharide linker on the protein, which then is degraded by β-glucuronidase, two β-galactosidases, and a β-xylosidase. The biosynthesis and breakdown of the main GAG chains (hyaluronate, keratan sulfate, chondroitin sulfate, dermatan sulfate and heparan sulfate) is described here.

Summary from Reactome (R-HSA-1630316), read 2026-09-23.