Glycosaminoglycans

Glycosaminoglycans (GAGs) are linear polymers composed of repeating disaccharides containing an amino sugar—either N-acetylglucosamine or N-acetylgalactosamine—paired with a uronic acid like glucuronic acid or iduronic acid. Their highly acidic nature due to sulfate and carboxylic groups gives them a negative charge, enabling them to attract water and cations in the extracellular matrix.

GAGs attract clouds of cations and water into the extracellular matrix, creating swelling and turgor pressure that helps tissues withstand compressive forces. When covalently attached to core proteins as proteoglycans and linked to hyaluronic acid, they form aggregates that provide load-bearing capacity and resistance to deformity in cartilage and other connective tissues.

The four main GAG groups are hyaluronic acid, chondroitin and dermatan sulfate, heparan sulfate, and keratan sulfate. They differ based on their sugar composition, the type of linkage between sugars, and the number and location of sulfate groups. Each type has distinct structural features and functional roles in various tissues.

Hyaluronic acid is used in eye drops to maintain eyeball shape and lubricates joints. Chondroitin is prescribed to treat osteoarthritis and coronary artery disease. Keratan sulfate is a major corneal component essential for corneal development and transparency. Dermatan sulfate regulates blood coagulation, wound repair, and infection response across various organs.

Due to their polar nature, GAGs attract and retain water molecules, making them excellent lubricants and shock absorbers in animal bodies. Hyaluronic acid, a major constituent of synovial tissue, serves as a ground substance in connective tissues and helps lubricate joints while binding cells together, reducing friction and impact stress.

Hyaluronic acid helps skin stretch and flex, thereby reducing wrinkles and maintaining tissue elasticity. As a non-sulfated GAG, it serves as a ground substance in various connective tissues and contributes to the overall hydration and structural integrity of the extracellular matrix throughout the body.

Most GAGs are covalently attached to core proteins, forming proteoglycans that populate the extracellular space of connective tissue. In cartilage, these proteoglycans are linked to hyaluronic acid, creating proteoglycan aggregates. This organization allows GAGs to attract cations and water, generating the turgor pressure necessary for tissue support and resilience.