GAGs

Glycosaminoglycans (GAGs) are long, unbranched, negatively charged polysaccharides that form a major component of the extracellular matrix and cell surfaces. They consist of repeating disaccharide units of uronic acid and amino sugar; most are sulfated, imparting negative charge. Most GAGs are covalently attached to core proteins to form proteoglycans; hyaluronic acid is a unique, non-sulfated GAG that is not covalently linked to proteins and can exist as a free polysaccharide.

Common GAGs include heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. Heparan sulfate and heparin typically contain iduronic acid and diverse sulfation patterns that bind growth factors and modulate signaling; chondroitin sulfate and dermatan sulfate regulate matrix structure and interact with collagen and growth factors; keratan sulfate is abundant in cornea and cartilage, with various sulfation patterns. Hyaluronic acid provides hydrated, space-filling properties and serves as a backbone for proteoglycans.

Biosynthesis occurs in the Golgi, where a linkage region on serine residues of core proteins initiates proteoglycan formation; hyaluronic acid is synthesized at the plasma membrane by hyaluronan synthases and extruded. Degradation occurs in lysosomes through specific enzymes; deficiencies cause mucopolysaccharidoses, a group of lysosomal storage diseases.

Clinical relevance and applications include the anticoagulant use of heparin; hyaluronic acid is employed in dermatology, ophthalmology, and joint therapy; dietary chondroitin sulfate is marketed with mixed evidence for efficacy. Analytical approaches for GAGs include disaccharide composition analysis by high-performance liquid chromatography after enzymatic digestion, mass spectrometry, and nuclear magnetic resonance spectroscopy.