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Fucose-1-Phosphate Guanylyltransferase (FPGT)

  • Risto Renkonen
Reference work entry

Abstract

l-fucose is an important monosaccharide in glycosylated proteins. Fucosylation plays a pivotal important role in cell signaling events related to inflammation, fertilization, development, and tumor metastasis programmed cell death (Becker 2003; Luhn 2012). The fucosyl donor for these fucosylated glycans decorating glycoproteins is GDP-beta-l-fucose. Two alternate pathways exist for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-d-mannose to GDP-beta-l-fucose via three enzymatic reactions. The alternative salvage pathway yields GDP-fucose derived directly from fucose. This route utilizes fucose first transported into the cytosol from an extracellular origin or fucose that is liberated from fucosylated glycans in the lysosome and then transported into the cytosol. Two enzymes participate in the salvage pathway; fucose kinase and Fucose-1-phosphate guanylyltransferase (GDP-fucose pyrophosphorylase, FPGT) with fucose-1-phosphate is the metabolic intermediate. Newly synthesized GDP-fucose is then transported into the Golgi lumen where it is used by various fucosyltransferases to generate fucosylated glycans finally decorating glycoproteins and glycolipids (Yurchenco 1977; Pastuszak 1998; Smith 2002; Becker 2003; Luhn 2012).

Keywords

Salvage Pathway Nucleotide Sugar Ammonium Citrate Cell Signaling Event Guanosine Diphosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Becker DJ, Lowe JB (2003) Fucose: biosynthesis and biological function in mammals. Glycobiology 13:41R–53RPubMedCrossRefGoogle Scholar
  2. Liu TW, Kaji H, Togayachi A, Ito H, Sato T, Narimatsu H (2012) A chemoenzymatic approach toward the identification of fucosylated glycoproteins and mapping of N-glycan sites. Glycobiology 22:630–637PubMedCrossRefGoogle Scholar
  3. Lühn K, Wild MK (2012) Human deficiencies of fucosylation and sialylation affecting selectin ligands. Semin Immunopathol 34:383–399PubMedCrossRefGoogle Scholar
  4. Niittymäki J, Mattila P, Roos C, Huopaniemi L, Sjöblom S, Renkonen R (2004) Cloning and expression of murine enzymes involved in the salvage pathway of GDP-L-fucose. Eur J Biochem 271:78–86PubMedCrossRefGoogle Scholar
  5. Niittymäki J, Mattila P, Renkonen R (2006) Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII. APMIS 114:539–548PubMedCrossRefGoogle Scholar
  6. Pastuszak I, Ketchum C, Hermanson G, Sjoberg EJ, Drake R, Elbein AD (1998) GDP-L-fucose pyrophosphorylase. Purification, cDNA cloning, and properties of the enzyme. J Biol Chem 273:30165–30174PubMedCrossRefGoogle Scholar
  7. Rabina J, Maki M, Savilahti EM, Jarvinen N, Renkonen R (2001) Analysis of nucleotide sugars from cell lysates by ion-pair solid-phase extraction and reversed-phase high-performance liquid chromatography. Glycoconj J 18:799–805PubMedCrossRefGoogle Scholar
  8. Smith PL, Myers JT, Rogers CE, Zhou L, Petryniak B, Becker DJ, Homeister JW, Lowe JB (2002) Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J Cell Biol 158:801–815PubMedCrossRefGoogle Scholar
  9. Wang W, Hu T, Frantom PA, Zheng T, Gerwe B, Del Amo DS, Garret S, Seidel RD 3rd, Wu P (2009) Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives. Proc Natl Acad Sci USA 106:16096–16101PubMedCrossRefGoogle Scholar
  10. Wiltshire SA, Leiva-Torres GA, Vidal SM (2011) Quantitative trait locus analysis, pathway analysis, and consomic mapping show genetic variants of Tnni3k, Fpgt, or H28 control susceptibility to viral myocarditis. J Immunol 186:6398–6405PubMedCrossRefGoogle Scholar
  11. Yurchenco PD, Atkinson PH (1977) Equilibration of fucosyl glycoprotein pools in HeLa cells. Biochemistry 16:944–953PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Haartman Institute, University of HelsinkiHelsinkiFinland

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