Glycosaminoglycan

For other uses of GAGs see Gag (disambiguation)

Chondroitin sulfate

Hyaluronan (-4GlcUAβ1-3GlcNAcβ1-)_n

Glycosaminoglycans^[1] (GAGs) or mucopolysaccharides^[2] are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose (six-carbon sugar) or a hexuronic acid, linked to a hexosamine (six-carbon sugar containing nitrogen).

Production

Protein cores made in the rough endoplasmic reticulum are posttranslationally modified by glycosyltransferases in the Golgi apparatus, where GAG disaccharides are added to protein cores to yield proteoglycans; the exception is the GAG hyaluronan, which is uniquely synthesized without a protein core and is "spun out" by enzymes at the cell surface directly into the extracellular space.

Function

This family of carbohydrates is essential or important for life.

GAGs form an important component of connective tissues. GAG chains may be covalently linked to a protein to form proteoglycans. Water sticks to GAGs; this is where the resistance to pressure comes from. The density of sugar molecules and the net negative charges attract cations, for example, Na+, which, after the sodium binds, attracts water molecules.

Some examples of glycosaminoglycan uses in nature include heparin as an anticoagulant, hyaluronan as a component in the synovial fluid lubricant in body joints, and chondroitins, which can be found in connective tissues, cartilage, and tendons.

Classification

Members of the glycosaminoglycan family vary in the type of hexosamine, hexose or hexuronic acid unit they contain (e.g. glucuronic acid, iduronic acid, galactose, galactosamine, glucosamine).

They also vary in the geometry of the glycosidic linkage.

Examples of GAGs include:

Name	Hexuronic acid / Hexose	Hexosamine	Linkage geometry between predominant monomeric units	Unique features
Chondroitin sulfate	GlcUA or GlcUA(2S)	GalNAc or GalNAc(4S) or GalNAc(6S) or GalNAc(4S,6S)	-4GlcUAβ1-3GalNAcβ1-	Most prevalent GAG
Dermatan sulfate	GlcUA or IdoUA or IdoUA(2S)	GalNAc or GalNAc(4S) or GalNAc(6S) or GalNAc(4S,6S)	-4IdoUAβ1-3GalNAcβ1-	Distinguished from chondroitin sulfate by the presence of iduronic acid, although some hexuronic acid monosaccharides may be glucuronic acid.[3]
Keratan sulfate	Gal or Gal(6S)	GlcNAc or GlcNAc(6S)	-3Gal(6S)β1-4GlcNAc(6S)β1-	Keratan sulfate type II may be fucosylated.[4]
Heparin	GlcUA or IdoUA(2S)	GlcNAc or GlcNS or GlcNAc(6S) or GlcNS(6S)	-4IdoUA(2S)α1-4GlcNS(6S)α1-	Highest negative charge density of any known biological molecule
Heparan sulfate	GlcUA or IdoUA or IdoUA(2S)	GlcNAc or GlcNS or GlcNAc(6S) or GlcNS(6S)	-4GlcUAβ1-4GlcNAcα1-	Highly similar in structure to heparin, however heparan sulfates disaccharide units are organised into distinct sulfated and non-sulfated domains.[5]
Hyaluronan	GlcUA	GlcNAc	-4GlcUAβ1-3GlcNAcβ1-	The only GAG that is exclusively non-sulfated

Abbreviations

• GlcUA = β-D-glucuronic acid
• GlcUA(2S) = 2-O-sulfo-β-D-glucuronic acid
• IdoUA = α-L-iduronic acid
• IdoUA(2S) = 2-O-sulfo-α-L-iduronic acid
• Gal = β-D-galactose
• Gal(6S) = 6-O-sulfo-β-D-galactose
• GalNAc = β-D-N-acetylgalactosamine
• GalNAc(4S) = β-D-N-acetylgalactosamine-4-O-sulfate
• GalNAc(6S) = β-D-N-acetylgalactosamine-6-O-sulfate
• GalNAc(4S,6S) = β-D-N-acetylgalactosamine-4-O, 6-O-sulfate
• GlcNAc = α-D-N-acetylglucosamine
• GlcNS = α-D-N-sulfoglucosamine
• GlcNS(6S) = α-D-N-sulfoglucosamine-6-O-sulfate

References

1. ^ "glycosaminoglycan" at Dorland's Medical Dictionary
2. ^ "mucopolysaccharide" at Dorland's Medical Dictionary
3. ^ Trowbridge JM, Gallo RL. (2002). "Dermatan sulfate: new functions from an old glycosaminoglycan". Glycobiology 12 (9): 117R–125R. doi:10.1093/glycob/cwf066. PMID 12213784. 
4. ^ Funderburgh JL. (2000). "Keratan sulfate: structure, biosynthesis, and function". Glycobiology 10 (10): 951–958. doi:10.1093/glycob/10.10.951. PMID 11030741. 
5. ^ Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V.. Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59. 

See also

• Mucopolysaccharidosis (lysosomal storage diseases)
• Lipopolysaccharide

External links

• Proteoglycans and Glycosaminoglycans at Lancaster University
• Illustration at scientificpsychic.com
• The Role of Mucopolysaccharides in good health
• King M. 2005. Glycosaminoglycans. Indiana University School of Medicine Accessed December 31, 2006.
• MeSH Glycosaminoglycans
• MRI evaluation of glycosaminoglycan loss (dGEMRIC evaluation)