module: dmel_gdp_fucose_biosynthesis
title: De novo GDP-fucose biosynthesis in Drosophila melanogaster
label: De novo GDP-fucose biosynthesis
module_type: METABOLIC_PATHWAY
description: >-
  GDP-L-fucose is the donor substrate for fucosyltransferases, including the
  O-fucosyltransferase that modifies Notch EGF repeats and the Golgi
  fucosyltransferases that fucosylate N-glycans. Drosophila makes it de novo
  from GDP-mannose in the cytosol: GDP-mannose 4,6-dehydratase (Gmd) forms
  GDP-4-keto-6-deoxymannose, and GDP-L-fucose synthase (Gmer) epimerizes and
  reduces this intermediate to GDP-L-fucose. GDP-fucose is then carried into
  the secretory pathway by two transporters, the Golgi GDP-fucose transporter
  (Gfr) and the endoplasmic reticulum transporter Efr. Loss of Gmd or of both
  transporters impairs Notch O-fucosylation and Notch signaling.
summary: >-
  Gmd and Gmer convert GDP-mannose to GDP-fucose, which Gfr and Efr import
  into the Golgi and endoplasmic reticulum.
concepts:
  - {id: GO:0042351, label: "'de novo' GDP-L-fucose biosynthetic process"}
parts:
  - id: gdp_mannose_dehydration
    label: GDP-mannose dehydration
    role: GDP-mannose to GDP-4-keto-6-deoxymannose
    genes: [Gmd]
    function: {id: GO:0008446, label: "GDP-mannose 4,6-dehydratase activity"}
  - id: gdp_fucose_synthesis
    label: GDP-L-fucose synthesis
    role: GDP-4-keto-6-deoxymannose to GDP-L-fucose
    genes: [Gmer]
    function: {id: GO:0050577, label: GDP-L-fucose synthase activity}
  - id: gdp_fucose_transport
    label: GDP-fucose import into the secretory pathway
    role: GDP-fucose transport into Golgi and endoplasmic reticulum
    description: >-
      Gfr imports GDP-fucose into the Golgi; Efr acts in the endoplasmic
      reticulum and also transports other nucleotide sugars.
    genes: [Gfr, Efr]
    complex: false
    unit_functions:
      Gfr: {id: GO:0005457, label: GDP-fucose transmembrane transporter activity}
    roles:
      Gfr: Golgi GDP-fucose transporter
      Efr: endoplasmic reticulum nucleotide-sugar transporter
connections:
  - source: gdp_mannose_dehydration
    target: gdp_fucose_synthesis
    connection_type: PRECEDES
    description: The Gmd product is converted to GDP-L-fucose by Gmer.
  - source: gdp_fucose_synthesis
    target: gdp_fucose_transport
    connection_type: PRECEDES
    description: Cytosolic GDP-L-fucose is imported into the secretory pathway.
notes: >-
  Boundary. The module covers the four FlyBase members. GDP-mannose supply is
  modelled in the GDP-mannose biosynthesis module; the fucosyltransferases that
  consume GDP-fucose (for example O-fut1 and FucT6) are downstream and not
  parts. Drosophila is reported to lack the fucose salvage pathway, so the de novo route is its source of GDP-fucose.
group: GDPFUC