Glycoconjugates pathways

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... 

How, exactly, retinol affects protein glycosylation is not yet known, but the formation of retinol phosphate, the D-mannosylation of retinol phosphate by GDP-Man, and the transfer of Man from D-mannosyl (retinol phosphate) to pronase-sensitive glycoconjugates are well established.5857,59 On the other hand, the formation and role of other gly-cosyl esters of retinol phosphate are still controversial.2,80 It is very probable that the D-mannosylation of retinol phosphate, and also the transfer of Man from this lipid derivative to protein, are catalyzed by enzymes different from those involved in the dolichol pathway,81-83 and this finding points to the different physiological roles of Man-P-Dol and D-mannosyl (retinol phosphate). Thus, whereas Man-P-Dol can serve to D-mannosylate dolichol diphosphate-linked oligosaccharides (see Section III), such a role has not been found for D-mannosyl (retinol phosphate).81,83... 

Both transferases from the Leloir and non-Leloir pathways have been employed for the in vitro synthesis of oligosaccharides and glycoconjugates. Glycosidases have also been exploited for synthesis. The function of glycosidases in vivo is to cleave glycosidic bonds,... 

Duverger, E., Pellerin-Mendes, C., Mayer, R., Roche, A.C. and Monsigny, M. (1995) Nuclear import of glycoconjugates is distinct from the classical NLS pathway. J. Cell Sci., 108, 1325-1332. 

In this context, the aim of our work is to provide well defined enzyme systems, to utilize them for the synthesis of these partly instable and very expensive nucleotide sugars, and finally to combine them with glycosyltransferases for glycoconjugate synthesis. In the following sections, I will present a summary of our work on the basis of the biosynthesis pathways for primary and secondary nucleotide sugars. 

Many extracellular proteins are glycoconjugates, containing covalently bound polysaccharides that contribute to stability of the protein and may have a signaling function in cellular targeting. Carbohydrate residues are attached to proteins during secretion from the cell by specialized glycosyl transferases localized in the secretory pathway... 

Cacan R, Verbert A (1995) Glycosyltransferases of the phosphodolichol pathways. In Verbert A (ed) Methods on glycoconjugates. Harwood Academic Publishers, Switzerland, p 191... 

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