Glycosaminoglycans

What is Glycosaminoglycans?

Glycogen and starch are both composed of glucose units. Besides, starch is a form of stored energy in plants, which is digested with amylases, and insoluble in water. In animals, glycogen exists in the form of stored energy. Cellulose is the primary structural component in plants and is indigestible by humans. Some other polysaccharides, such as xanthan gum, are present in the bacterium capsule.

They contain protein cores, made in the endoplasmic reticulum and modified post-translationally by the Golgi body. Glycosaminoglycan disaccharides are added to the protein cores and produce proteoglycans. These are the important components of connective tissues and much essential to life. Also, the GAG chains are covalently bonded to other proteins such as cytokines, chemokines, morphogens, enzyme adhesion molecules forming proteoglycans, and growth factors.

What are Carbohydrates?

Carbohydrates are the bio-polymers composed of monomer units known as monosaccharides. Carbohydrates can be classified into various types based on the number of monosaccharide units present in them.

• Monosaccharides: 

The monomer units cannot be further hydrolyzed.

• Oligosaccharide: 

Hydrolysis of oligosaccharides supplies 2-10 units of monosaccharides.

• Polysaccharides: 

These are composed of 10-100 or even more monosaccharide units.

Polysaccharides are described as complex carbohydrates that contain multiple monosaccharides with the other structures. They are also known as glycans because the monosaccharide units are bonded with the glycosidic linkages. Polysaccharides are branched and large molecules, which are amorphous in nature, often insoluble in water. These are non-sweet carbohydrates. Cellulose, starch, chitin, and glycogen are the best examples of polysaccharides.

Types of Glycosaminoglycans

• Homopolysaccharides

• Heteropolysaccharides

Homopolysaccharides are composed of similar types of monosaccharide units, whereas the heteropolysaccharides have different types of monosaccharide units. The general formula of polysaccharides can be given as Cn(H2O)n-1, where n falls between 200 and 2500.

Structure of Glycosaminoglycans

In general, glycosaminoglycans are linear and negatively charged polysaccharides that can be non-sulfate or sulfate with nearly 10-100 kilodalton molecular weights.

They can be classified into two types based on their structural units and linkage between the disaccharide units, as listed below.

• Sulfated GAGs: For example, dermatan sulfate (DS), chondroitin sulfate (CS), keratan sulfate (KS), heparin, and heparin sulfate (HS),

• Non-sulfated GAGs: An example is glycosaminoglycans hyaluronic acid (HA).

There are the disaccharides repeating units in the glycosaminoglycan chains, composed of uronic acid-like L-iduronic acid or D-glucuronic acid and amino sugar such as D-glucosamine or D-galactosamine. All these glycosaminoglycans differ in the hexosamine type, hexuronic or hexose acid unit, and the geometry of the glycosidic linkage between them.

[Image will be Uploaded Soon]

For example, the chondroitin sulfate and dermatan sulfate contain galactosamine and also called glycosaminoglycans. A few other glycosaminoglycans like heparin and heparin sulfate also contain glycosaminoglycan units.

• Chondroitin sulfate contains beta-D-glucuronate, which is linked to the 3rd carbon of N-acetylgalactosamine-4-sulfate. In contrast, heparin is a complex mixture of linear polysaccharides with anticoagulant properties and varies in the saccharide units' sulfation degree.

• The amino sugar in the glycosaminoglycans can be sulfated either on the non-acetylated nitrogen or C4 or C6.

• The sugar structure of GAGs can be sulfated at different positions; hence a simple octasaccharide contains over 1000,000 various sulfation sequences.

• There exist either 2-3 or 1-2 possible sulfation positions on the amino sugar and on the uronic acid, respectively, in the repeating unit of every glycosaminoglycan species.

• Since these positions are not always sulfated, 16 to 48 multiple disaccharide units can exist based on the sulfation position combination.

Function of Glycosaminoglycans 

• Glycosaminoglycans (otherwise called GAGs) participate in various biological processes through the regulation of their different protein partners known as proteoglycan.

• The GAG's large structural diversity makes them approachable for structural, biochemical, molecular modeling, and biology and made them useful in the new drug discovery.

• The underlying sulfation patterns and conformational flexibility of GAGs are responsible for the complexity of GAG-protein interaction.

• Primarily negatively charged molecules prepared in animal cells are phospholipids, glycosaminoglycans (GAGs), and nucleic acids or ribonucleic deoxyribonucleic acid.

• The glycosaminoglycans, which are negatively charged, cover the animal cell surfaces and interact with hundreds of extracellular signaling molecules.

• Due to their structural complexity, they have been claimed to exist as the most information-dense biopolymers that are found in nature. These biomolecules are related to the transfer of genetic information in animals.

Applications of Glycosaminoglycans

There are many new projects currently going on, based on different applications of glycosaminoglycans. Some of them are as follows.

• Inhibitors in FGF/FGFR Signaling and GAG-based Activators.

• In the regulation of FGFR/FGF Signaling.

• Proteoglycans and Serum GAGs as biomarkers for lung cancer.

• Joint Specificity in Rheumatoid Arthritis, on the basis of GAG.

Hyaluronic acid represents various essential functions in signaling activity during wound healing, embryonic morphogenesis, and vascular & pulmonary diseases. Also, it acts as synovial joint lubrication and helps in joint movement and as a wetting agent, space filler, and flow barrier within the synovium. It influences cancer progression and protects cartilage surfaces.