glycosaminoglycanes

Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units that typically include an amino sugar (such as N-acetylglucosamine or N-acetylgalactosamine) and a uronic acid or galactose. Most GAGs are highly sulfated and carry a strong negative charge, which promotes hydration and resilience of the extracellular matrix. With the exception of hyaluronic acid, GAG chains are covalently attached to protein cores to form proteoglycans; hyaluronic acid is not protein-bound and can form large aggregates with proteoglycans in the extracellular matrix.

The major classes of GAGs include heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. Heparan sulfate and heparin are highly sulfated and participate in regulation of coagulation, inflammation, and growth-factor signaling. Chondroitin sulfate and dermatan sulfate are abundant in cartilage and connective tissue, contributing to structural integrity. Keratan sulfate is found in the cornea and cartilage, while hyaluronic acid provides space-filling properties, lubrication, and high molecular weight in synovial fluid and tissues.

Biosynthesis occurs mainly in the Golgi apparatus for most GAGs, via specific glycosyltransferases; hyaluronic acid is synthesized at the plasma membrane by hyaluronan synthases. Degradation takes place in lysosomes through specialized hydrolases and sulfatases. Defects in these enzymes cause mucopolysaccharidoses, a group of lysosomal storage disorders such as Hurler and Hunter syndromes.

GAGs contribute to tissue hydration, mechanical resilience, and regulation of cell behavior by interacting with cytokines, growth factors, and cell-surface receptors. They are also clinically significant, featuring in anticoagulant therapy (heparin) and in various diagnostic and therapeutic contexts related to GAG biology.