Biosynthesis of sialic acids

The biosynthesis of sialic acids begins with D-glucose (Glc), the commoDr precursor of all monosaccharides in complex carbohydrate metabolism. The complete pathway provides both N-acetylhexosamines and sialic acids for biosynthesis and can be divided up into two halves with UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) as the central metabolite. The individual steps are presented in the schemes in Figs. 1 and 2, and a summary of the regulation on the complete pathways is shown in Fig. 9. 

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The pathway of the biosynthesis of Neu5Ac demonstrates the origin of sialic acids from the cellular hexose and hexosamine pools. These sugars are, therefore, suitable components for the study of the biosynthesis of sialic acid. However, only ManNAc has been shown to be a relatively specific precursor of sialic acids, as may be seen from the distribution of radioactivity between the individual monosaccharides of glycoconjugates after incubation. Injections of radioactive ManNAc into animals, or incubation of surviving tissue slices or individual cells with this compound, give incorporation of label mainly into the sialic acids.226 227... 

N-acetylglucosamine (see Chapter 9) is a component of glycoproteins, connective tissue proteoglycans, and complex lipids. It may be synthesized in the human organism from fructose-6-phosphate, as indicated in Figure 18.17. N-acetylglucosamine is also a precursor of N-acetylmannosamine, which along with pyruvic acid participates in the biosynthesis of sialic acid. 

The biosynthesis of sialic acid has been studied in liver and bacteria. Since several alternative pathways exist, it is important that the biosynthesis of this compound also be studied in the brain. The synthesis of sialic add starts with the formation of acetylglucosa-mine. Enzyme preparations obtained from Neurospora... 

The biosynthesis of sialic acid conjugates requires three dedicated en2ymatic steps along the general Leloir pathway, which consist of a carbohgation step to construct the special extended sialic acid backbone, followed by nucleotide activation of the sugar and its regio- and stereospecific transfer to a suitable acceptor moiety (Scheme 17.1). For the most common sialic acid, namely NeuSAc, synthesis... 

Procedures have been described for the assay of protein-bound carbohydrate in sera and urine from normal children and from patients with sialuria. It was concluded that sialuria is not associated with an anomalous metabolism of glycoproteins, but with an anomalous biosynthesis of sialic acid. 

Bergwerfif, A. A., Hulleman, S.H.D., Kamerling, J. P., Vliegenthart, J.F.G., Shaw, L., Reuter, G., and Schauer, R., 1992, Nature and biosynthesis of sialic acids in the starfish Asterias rubens. Identification of sialo-oligomers and detection of S-adenosyl-L-methionine N-acylneuraminate... 

Schauer, R., 1978b, Biosynthesis of sialic acids. Methods Enzymol. 50 374-386. 

Blacklow, R. S., and Warren, L., 1962, Biosynthesis of sialic acids by Neisseria meningitidis, J. Biol. Chem. 237 3520-3526. 

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