Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units that consist of an amino sugar (either N-acetylglucosamine or N-acetylgalactosamine) and a uronic acid (either glucuronic acid or iduronic acid) or a galactose. GAGs are important components of the extracellular matrix (ECM) in connective tissues and are also found on the surface of some cell types.
Glycosaminoglycans have a strong affinity for water due to their highly negative charge, which arises from the presence of sulfate and carboxyl groups on their sugar residues. This property enables GAGs to form hydrated gel-like structures, which contribute to the compressive resistance and viscoelastic properties of the ECM.
There are four main classes of glycosaminoglycans:
- Hyaluronic acid: This is the only GAG that does not contain sulfate groups and is not covalently attached to a core protein. Hyaluronic acid plays a crucial role in maintaining the hydration and viscosity of the ECM, and is abundant in the skin, synovial fluid, and vitreous humor of the eye. It is also involved in cell signaling, wound healing, and tissue regeneration.
- Chondroitin sulfate: This GAG is commonly found in cartilage, bone, and skin, and contributes to the mechanical properties of these tissues. It is covalently attached to core proteins to form proteoglycans such as aggrecan, which is a major component of cartilage ECM.
- Dermatan sulfate: Also known as chondroitin sulfate B, dermatan sulfate is found in the skin, blood vessels, heart valves, and tendons. It contributes to the viscoelastic properties of the ECM and is involved in the regulation of coagulation and cell adhesion.
- Heparan sulfate: This GAG is found on cell surfaces and in basement membranes, where it is covalently attached to core proteins to form proteoglycans such as syndecan and perlecan. Heparan sulfate plays a role in cell signaling, growth factor binding, and cell adhesion.
- Keratan sulfate: This GAG is found in cartilage, cornea, and intervertebral discs. It is covalently attached to core proteins to form proteoglycans such as lumican and keratocan. Keratan sulfate contributes to the structural integrity and transparency of the cornea.
Glycosaminoglycans play a crucial role in various physiological processes, including cell signaling, tissue hydration, cell adhesion, and the regulation of tissue repair and development. Abnormalities in GAG synthesis or degradation can lead to various connective tissue disorders, such as mucopolysaccharidoses, which are a group of inherited metabolic diseases characterized by the accumulation of partially degraded GAGs in cells and tissues.