Glycans & sialic acid

Glycans are sugar chains composed of saccharides aggregation that are found in the surface of eukaryotic cells and bacteria attaching to lipids and proteins. These saccharides contribute to different functions to the cell that include: (1) Extracellular matrix formation; (2) Structural support; (3) Signal transduction; and (4) Contribute to protein folding change. The study of glycans has emerged as a field of biochemistry known as “Glycobiology

Glycans are found on the cell surface, and they mediate cell-to-cell, and cell-to-extracellular fluid communication. The most common glycosulation of proteins is known as “O-glycosylation” and “N-glycosylation

Sialic acids are diverse family of 9-carbon sugars that are found attached to the “Outer” surface of the cells’ glycans. Silaic acids have “Negative charge” and are “Hydrophilic” molecules. The negative charge expressed by body cells (e.g., RBCs) is due to sialic acids. Also, the negative charge of the silica acids in the glomerular basement membrane assists in preventing the filtration of proteins, which are also negatively-charged

Sialic acids work as “Binding sites” for many pathogens and toxins. Many pathogens bind to sialic acids on the cell surface, which will cause protein channel misshape opening the cell membrane to pathogens; examples include: Human influenza A (Binds to Hemagglutinin), Plasmodium falciparum (Binds to EBA-175), Clostridium botulinum (Binds to Toxin), Helicobacter pylori (Binds to SabA), E. Coli (Binds to Polysialic acid), Group B streptococcus (Binds to Sialylated N-acetyllactosamine), Group A streptococcus (Binds to Hyaluronan), and Campylobacter jejuni (Binds to Sialylated ganglioside-like glycans)  

Many pathogens decorates themselves externally with silica acids that mimics the body’s own cellular silica acids, evoking the immune system to attack the pathogens and the normal cells that contain the same silaic acids shapes; this is known as “Molecular mimicry” in immunity. A very famous example is “Gullian-Barre syndrome”, in which the body forms antibodies against “Campylobacter jejuni”, which will also attack the nerve sheaths of peripheral nerves, causing demyelination. Campylobacter jejuni has sialiac acids that are similar to the peripheral nerves sheaths, resulting in molecular mimicry attack. The same mechanism of disease is seen in Tetanus and Botulism 

 

Selected references

1. Varki A. Sialic acids in human health and disease. Trends in Molecular Medicine 2008; 14(8); 351-360

2. Khatua B et al. Sialic acids siglec interaction: A unique strategy to circumvent innate immune response by pathogens. Indian J Med Res 2013; 138: 648-662