Publisher Summary This chapter discusses the chemistry, metabolism, and biological functions of sialic acids. Interest in the sialic acids has rapidly increased in recent years, especially because of the reorganization of their involvement in the regulation of a great variety of biological phenomena. The occurrence of sialic acids in plants has never unequivocally been established, although some positive reports exist. The acylneuraminic acids can be released from their glycosidic linkages either by dilute (aqueous or methanolic) acids or sialidases. The unequivocal determination of sialic acids occurring in low concentrations in many biological materials is rather difficult, and this explains the many errors that have been made in this field. The biosynthesis of N-acetylneuraminic acid (Neu5Ac) is briefly reported in this chapter and more attention is given to the enzyme reactions modifying this compound. Little information is available about the role of the modifications of sialic acid resulting in a species- and tissue-specific distribution of different N,O-acylated and O-methylated sialic acids.

Chemistry, Metabolism, and Biological Functions of Sialic Acids

https://www.uni-kiel.de/Biochemie/AGSch/pdf/reviews/82_Schauer_2009_Current-Opinion-in-Structural-Biology.pdf

Sialic Acids as Regulators of Molecular and Cellular Interactions

Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system.

https://www.physiology.org/doi/pdf/10.1152/physrev.00033.2013

Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration

https://www.cell.com/cell/pdf/0092-8674(91)90008-M.pdf

A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells.

Neuronal development in the Drosophila retina: monoclonal antibodies as molecular probes.

The discovery and the widespread occurrence of the sialic acids in mammalian tissues (Blix 1936, Klenk 1941) has been correlated with a range of different biological functions (see chapter J) which continues to expand. Although the literature on sialic acid occurrence is large (Gottschalk 1960, Blix and Jeanloz 1969, Tuppy and Gottschalk 1972, Schauer 1973, Ng and Dain 1976), it has been essentially limited to the vertebrates and some examples from the Echinodermata and Bacteria. Only one survey of sialic acid distribution in different phyla has been published (Warren 1963). Current data on sialic acid structure is compiled in Table 1, introducing the known spectrum of derivatives covered in this chapter.

Occurrence of Sialic Acids

New chromatographic system for the rapid analysis and preparation of colostrum sialyloligosaccharides.

The specificity of viral and bacterial sialidases for α(2–3)- and α(2–6)-linked sialic acids in glycoproteins

The wide occurrence of sialic acids in nature is an indication of their great biological importance. As is described in other chapters in this book, the identification of the sialic acids was pioneered in several laboratories, while the biosynthetic mechanism of sialic acid formation was elucidated essentially by the work of Roseman’s and Warren’s groups in the United States (see Roseman 1962, Warren 1972, Schachter and Roden 1973, McGuire 1976, Schachter 1978).

Metabolism of Sialic Acids

Gangliosides have been found to contain up to five sialic acid moieties bound to galactose residues in α, 2->3 linkages either at the end of the oligosaccharide chain or within the chain, and may form di- and trisialyl groups with α,2->8 linkages (1,2). N-Acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuG1) have been identified as the commonly occurring sialic acids in gangliosides, while the O-acetylated sialic acids occur less frequently. The 9-O-acetyl-N-acetylneuraminic acid has been found in gangliosides from a variety of vertebrates including man (3), and 4-O-acetyl-N-glycolylneuraminic acid (4-OAc-NeuGl) has been isolated from horse erythrocyte hematoside (4).

Anthony P. Corfield

Papers

Occurrence of Sialic Acids

New chromatographic system for the rapid analysis and preparation of colostrum sialyloligosaccharides.

The specificity of viral and bacterial sialidases for α(2–3)- and α(2–6)-linked sialic acids in glycoproteins

Metabolism of Sialic Acids

“Neuraminidase-Resistant” Sialic Acid Residues of Gangliosides