Reactome | GMDS dehydrates GDP-Man to GDP-DHDMan

GMDS dehydrates GDP-Man to GDP-DHDMan

Stable Identifier

R-HSA-6787632

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        GDP-fucose biosynthesis (Homo sapiens)
        
        GMDS dehydrates GDP-Man to GDP-DHDMan (Homo sapiens)

General

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The de novo synthesis pathway for GDP-L-fucose is a two step pathway starting from GDP-mannose. In the first step, GDP-mannose (GDP-Man) is dehydrated to GDP-4-dehydro-6-deoxy-alpha-D-mannose (GDP-DHDMan) by GDP-mannose 4,6 dehydratase (GMDS) (Sullivan et al. 1998, Ohyama et al. 1998). Fucosylation is one of the most important oligosaccharide modifications in cancer and inflammation. Defects in GMDS are involved in the progression of colorectal cancer (Nakayama et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
9603974	Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in Lec13 cells Lowe, JB, Ohyama, C, Smith, PL, Angata, K, Fukuda, MN, Fukuda, M	J. Biol. Chem.	1998
23922970	Mutation of GDP-mannose-4,6-dehydratase in colorectal cancer metastasis Shinzaki, S, Imai, T, Kamada, Y, Murata, K, Moriwaki, K, Nakayama, K, Miyoshi, E	PLoS ONE	2013
9525924	Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro Xu, GY, Potvin, B, Sullivan, FX, Rouse, J, Kumar, R, Chang, XJ, Kriz, R, Cumming, DA, Boodhoo, A, Stahl, M	J. Biol. Chem.	1998