Sialic acid

Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid (Neu5Ac or NANA). Sialic acids are found widely distributed in animal tissues and to a lesser extent in other species ranging from plants and fungi to yeasts and bacteria, mostly in glycoproteins and gangliosides. The amino group generally bears either an acetyl or glycolyl group but other modifications have been described. The hydroxyl substituents may vary considerably: acetyl, lactyl, methyl, sulfate, and phosphate groups have been found. The term "sialic acid" (from the Greek for saliva, σίαλον/sialon) was first introduced by Swedish biochemist Gunnar Blix in 1952.

Structure


The numbering of the sialic acid structure begins at the carboxylate carbon and continues around the chain. The configuration which places the carboxylate in the axial position is the alpha-anomer.



Biosynthesis
In bacterial systems, sialic acids are biosynthesized by an aldolase enzyme. The enzyme uses a mannose derivative as a substrate, inserting three carbons from pyruvate into the resulting sialic acid structure. These enzymes can be used for chemoenzymatic synthesis of sialic acid derivatives.



Function
Sialic acid-rich glycoproteins (sialoglycoproteins) bind selectin in humans and other organisms. Metastatic cancer cells often express a high density of sialic acid-rich glycoproteins. This helps these late-stage cancer cells enter the blood stream.

Sialic acid also plays an important role in human influenza infections. The influenza viruses (orthomyxoviridae) have hemagglutinin activity (HA) glycoproteins on their surface that bind to sialic acids found on the surface of human erythrocytes and on the cell membranes of the upper respiratory tract. This is the basis of hemagglutination when viruses are mixed with blood cells, and entry of the virus into cells of the upper respiratory tract.

Sialic acid-rich oligosaccharides on the glycoconjugates (glycolipids, glycoproteins, proteoglycans) found on surface membranes help keep water at the surface of cells. The sialic acid-rich regions contribute to creating a negative charge on the cells' surface. Since water is a polar molecule with partial positive charges on both hydrogen atoms, it is attracted to cell surfaces and membranes. This also contributes to cellular fluid uptake.

Sialic acid can "hide" mannose antigens on the surface of host cells or bacteria from mannose-binding lectin. This prevents activation of complement.

Sialic acid in the form of polysialic acid is an unusual posttranslational modification that occurs on the neural cell adhesion molecules, NCAM. In the synapse, the strong negative charge of the polysialic acid prevents NCAM cross-linking of cells.