Nucleotide sugars metabolism explained

In nucleotide sugar metabolism a group of biochemicals known as nucleotide sugars act as donors for sugar residues in the glycosylation reactions that produce polysaccharides.^[1] They are substrates for glycosyltransferases.^[2] The nucleotide sugars are also intermediates in nucleotide sugar interconversions that produce some of the activated sugars needed for glycosylation reactions.^[1] Since most glycosylation takes place in the endoplasmic reticulum and golgi apparatus, there are a large family of nucleotide sugar transporters that allow nucleotide sugars to move from the cytoplasm, where they are produced, into the organelles where they are consumed.^{[3] [4]}

Nucleotide sugar metabolism is particularly well-studied in yeast,^[5] fungal pathogens,^[6] and bacterial pathogens, such as E. coli and Mycobacterium tuberculosis, since these molecules are required for the synthesis of glycoconjugates on the surfaces of these organisms.^{[7] [8]} These glycoconjugates are virulence factors and components of the fungal and bacterial cell wall. These pathways are also studied in plants, but here the enzymes involved are less well understood.^[9]

Notes and References

1. Ginsburg V . Comparative biochemistry of nucleotide-linked sugars . Prog. Clin. Biol. Res. . 23 . 595–600 . 1978 . 351635.
2. Rademacher T, Parekh R, Dwek R . Glycobiology . Annu Rev Biochem . 57 . 785–838 . 1988 . 3052290 . 10.1146/annurev.bi.57.070188.004033.
3. Handford M, Rodriguez-Furlán C, Orellana A . Nucleotide-sugar transporters: structure, function and roles in vivo . Braz. J. Med. Biol. Res. . 39 . 9 . 1149–58 . 2006 . 16981043 . 10.1590/s0100-879x2006000900002. free .
4. Gerardy-Schahn R, Oelmann S, Bakker H . Nucleotide sugar transporters: biological and functional aspects . Biochimie . 83 . 8 . 775–82 . 2001 . 11530210 . 10.1016/S0300-9084(01)01322-0.
5. Dean N, Zhang YB, Poster JB . The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae. . J. Biol. Chem. . 272 . 50 . 31908–14. 1997 . 9395539 . 10.1074/jbc.272.50.31908. free .
6. Nishikawa A. . Poster J.B. . Jigami Y. . Dean N. . Molecular and phenotypic analysis of CaVRG4, encoding an essential Golgi apparatus GDP-mannose transporter. . J. Bacteriol. . 184. 50 . 29–42. 2002 . 11741841 . 134776. 10.1128/JB.184.1.29-42.2002 .
7. Samuel G, Reeves P . Biosynthesis of O-antigens: genes and pathways involved in nucleotide sugar precursor synthesis and O-antigen assembly . Carbohydr. Res. . 338 . 23 . 2503–19 . 2003 . 14670712 . 10.1016/j.carres.2003.07.009.
8. Ma Y, Pan F, McNeil M . Formation of dTDP-rhamnose is essential for growth of mycobacteria . J. Bacteriol. . 184 . 12 . 3392–5 . 2002 . 12029057 . 10.1128/JB.184.12.3392-3395.2002 . 135104.
9. Seifert GJ . Nucleotide sugar interconversions and cell wall biosynthesis: how to bring the inside to the outside . Curr. Opin. Plant Biol. . 7 . 3 . 277–84 . 2004 . 15134748 . 10.1016/j.pbi.2004.03.004.