glycosaminoglycan

Definition: Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit.

They are called GAGs because one of the two sugar residues in the repeating disaccharide is always an amino sugar (N-acetylglucosamine or N-acetylgalactosamine), which in most cases sulfated.

Because there are sulfate or carboxyl groups on most of their sugar residues, GAG are highly negatively charged.

Glycosaminoglycans form long-chain complex carbohydrates that are linked with proteins to form proteoglycans. They are abundant in the ground substance of connective tissue.

The enzymes involved in the degradation of these molecules cleave terminal sugars from the polysaccharide chains disposed along a polypeptide or core protein.

Structure

The repeating disaccharide unit consists of an N-acetyl-hexosamine and a hexose or hexuronic acid, either or both of which may be sulfated. The combination of the sulfate group and the carboxylate groups of the uronic acid residues gives them a very high density of negative charge.

Function

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

Glycoaminoglycan and proteoglycan molecules in connective tissue form a highly dydrated, gel-like ground substance in which the fibrous proteins are enbedded. The polysaccharide gel resists compressive forces on the matrix and the collagen biber provide tensile strength. The aqueous phase of the polysaccharide gel permist the rapid diffusion of nutrients, metabolites and hormornes between the blood and the tissue cells.

Proteoglycans

GAG chains may be covalently linked to a protein to form proteoglycans.

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 hyaluronan, which is uniquely synthesized without a protein core and is "spun out" by enzymes at cell surfaces directly into the extracellular space.

Examples of proteoglycans

 chondroitin sulfate
 dermatan sulfate
 keratan sulfate
 hyaluronan
 heparin
 heparan sulfate

Pathology

When there is a block in the removal of a terminal sugar, the remainder of the polysaccharide chain is not further degraded, and thus the long unbranched chains accumulate within lysosomes in various tissues and organs of the body, causing mucopolysaccharidoses (MPS). Severe somatic and neurologic changes result.

The proteoglycans that accumulate in mucopolysaccharidoses (MPS) are dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate.

See also

 proteoglycans
 carbohydrates
 mucopolysaccharidoses