Glycosaminoglycans (GAGs) are long, unbranched chains of repeating disaccharide units consisting of an amino sugar (either N-acetylglucosamine or N-acetylgalactosamine) and a uronic acid (either glucuronic acid or iduronic acid) or galactose. GAGs can be found either attached to core proteins as part of proteoglycans or as free molecules in the extracellular matrix (ECM) and on cell surfaces. They are highly negatively charged due to the presence of sulfate groups and carboxyl groups, which enable them to attract and retain water molecules.
GAGs contribute to the hydration, viscosity, and resistance to compression of the ECM, providing tissues with the ability to withstand mechanical stress. They also play a role in various biological processes, such as cell adhesion, growth factor signaling, and tissue repair.
There are several types of GAGs, including:
- Hyaluronic acid: Unlike other GAGs, hyaluronic acid is not sulfated and is not covalently attached to a core protein. It is a major component of the ECM in connective tissues, synovial fluid, and vitreous humor of the eye. Hyaluronic acid plays a role in cell migration, tissue hydration, and lubrication.
- Chondroitin sulfate: Chondroitin sulfate is the most abundant GAG in the ECM and is primarily found attached to proteoglycans, such as aggrecan and versican. It is prevalent in cartilage, bone, and skin, where it contributes to the mechanical properties and resistance to compression of tissues.
- Dermatan sulfate: Dermatan sulfate is a GAG found in various connective tissues, such as skin, blood vessels, and heart valves. It is often attached to proteoglycans, such as decorin and biglycan. Dermatan sulfate is involved in cell adhesion, tissue repair, and the regulation of coagulation.
- Heparan sulfate: Heparan sulfate is a GAG that can be found attached to proteoglycans, such as perlecan and syndecans, on the cell surface and in the ECM. It is involved in cell adhesion, growth factor signaling, and the regulation of various physiological processes, such as blood coagulation and lipid metabolism.
- Keratan sulfate: Keratan sulfate is a GAG that can be found attached to proteoglycans, such as aggrecan and lumican, in various tissues, including cartilage, cornea, and intervertebral discs. It contributes to the mechanical properties and transparency of tissues.
Dysregulation of GAG synthesis or degradation can contribute to various pathological conditions, such as osteoarthritis, mucopolysaccharidoses, and cancer. Understanding the role and regulation of GAGs is essential for developing therapeutic strategies targeting tissue repair, regeneration, and disease progression.