Last revised by Kanwal Laique on 4 Jun 2023

Glycosaminoglycans (GAGs), formerly known as mucopolysaccharides, are biomolecules produced by almost all mammalian cells, as well as in many vertebrates and invertebrates, but have not been described in plants 1. They are constituent elements of proteoglycans and are found within the cells in the intracellular environment, on the cellular surface and the extracellular matrix. Due to their high polarity, they bind high amounts of water to their surroundings.

Glycosaminoglycans are complex carbohydrates composed of repeating disaccharide units that are built of amino sugars and uronic acid or galactose 1-4 and differ regarding their linkages between units, the position of sulfate groups and degree of sulfation and uronate epimerization 1,2. They feature a substantial degree of structural variability and can be broadly classified into the following classes 1-5:

  • chondroitin sulfate (CS)
  • dermatan sulfate (DS)
  • heparin/heparan sulfate (HS)
  • hyaluronan (HA)
  • keratan sulfate (KS)

Most glycosaminoglycans have uronic acid and sulfate groups on most of their units with hyaluronic acid being the only glycosaminoglycan without any sulfate group 2,3.

Glycosaminoglycans participate in a myriad of biological functions and play a role in almost all physiological activities of the body and many pathological conditions. This includes proteoglycan-mediated interactions which are also attributed to glycosaminoglycan chains 2-4. Major functions include the following 2-4:

  • maintenance of structural cell and tissue integrity
  • maintenance of homeostasis
  • interactions with cytokines, chemokines, growth factors, morphogens, enzymes and adhesion molecules
  • shock absorbing lubricating functions due to their water-binding capacities

Their interaction has a profound effect on the following physiological and pathological processes 2-4:

  • cell adhesion, cell migration
  • cell and tissue proliferation and differentiation including tissue development
  • cell membrane function and signaling
  • matrix organization
  • apoptosis
  • coagulation
  • inflammation, chemotaxis
  • lipid metabolism
  • angiogenesis
  • pathogen and viral infections
  • tumor progression, metastasis

Glycosaminoglycans are involved in cancer growth including signaling for cancer angiogenesis, cancer invasion and metastasis. Conversely, they are also involved in the suppression of tumor progression 2,4.

Among other tasks glycosaminoglycans regulate the surface coating of endothelial cells and leukocytes and are involved in the migration process as well as the cell-cell and cell-matrix interaction of inflammatory cells 2,3.

Due to their effect on tumor progression and their role in inflammatory processes, they serve as a target for the development of different therapeutics including anti-cancer and anti-inflammatory agents 2,3.

Changes in their structure or expression are seen in many pathological processes and therefore they can be used as biomarkers for disease progression 2.

Some tissue types like hyaline cartilage and myxoid matrix contain large amounts of glycosaminoglycans.

The first described function of glycosaminoglycans was the anticoagulation with heparin being discovered in 1917 by the American surgeon Jay McLean and the American physiologist William Henry Howell 3.

Clinical conditions and diseases related to glycosaminoglycans include the following disorders 2:

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