hyaluronic acid
Summary
Hyaluronic acid (hyaluronan) is a non-sulfated glycosaminoglycan (GAG) composed of repeating disaccharide units of D-glucuronic acid and N-acetylglucosamine. It is a major component of the extracellular matrix, synovial fluid, and vitreous humor, providing lubrication, hydration, and structural support. It is notably the only GAG not sulfated and not covalently attached to a core protein (not a proteoglycan).
Detail
Hyaluronic acid (HA) is synthesized at the plasma membrane by hyaluronan synthases (HAS1-3) rather than in the Golgi like other GAGs, and it can reach extremely high molecular weight (up to millions of Da). Structurally, it consists of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine linked by alternating β-1,4 and β-1,3 glycosidic bonds. Unlike other glycosaminoglycans (e.g., chondroitin sulfate, heparan sulfate, keratan sulfate, dermatan sulfate), HA is not sulfated and does not covalently bind to a core protein, though it can noncovalently interact with proteoglycans (e.g., aggrecan) via link proteins to form large aggregates in cartilage.
Clinical/Physiological significance: - Found abundantly in synovial fluid, vitreous humor, cartilage, skin, and umbilical cord (Wharton's jelly). - Provides viscoelasticity and lubrication in joints; degraded HA fragments can promote inflammation and angiogenesis. - Used clinically as intra-articular injections for osteoarthritis (viscosupplementation) to improve joint lubrication. - Widely used in cosmetic dermal fillers due to its water-binding capacity (can hold up to 1000x its weight in water) and biocompatibility. - Important in wound healing—present in high amounts in early wound matrix, facilitating cell migration. - CD44 is the primary cell surface receptor for HA, involved in cell adhesion, migration, and tumor metastasis (elevated HA-CD44 signaling seen in some cancers). - Hyaluronidase, an enzyme that degrades HA, is used clinically to increase tissue permeability (e.g., to aid drug diffusion) and is produced by some invasive bacteria (e.g., Streptococcus, Clostridium perfringens) as a virulence factor to spread through tissue planes.
High-yield boards association: Know that HA is a GAG that is not sulfated and not attached to a core protein, distinguishing it from other GAGs on biochemistry questions. Also relevant to pharmacology (fillers, viscosupplementation) and microbiology (hyaluronidase as a spreading factor in bacterial infections).
Sources
- First Aid for the USMLE Step 1
- Lippincott Biochemistry
- Robbins Basic Pathology
- Kaplan USMLE Step 1 Biochemistry Lecture Notes
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.