module: dmel_gdp_mannose_biosynthesis
title: GDP-mannose biosynthesis in Drosophila melanogaster
label: GDP-mannose biosynthesis
module_type: METABOLIC_PATHWAY
description: >-
  GDP-mannose is the mannose donor for N-glycan precursor assembly, GPI anchors
  and protein O-mannosylation (through dolichol-phosphate-mannose), and the
  precursor of GDP-fucose. It is made in the cytosol from hexose
  6-phosphates. Hexokinases phosphorylate glucose or mannose; glucose
  6-phosphate is isomerized to fructose 6-phosphate by glucose-6-phosphate
  isomerase (Pgi), and mannose-6-phosphate isomerase (Mpi) interconverts
  fructose 6-phosphate and mannose 6-phosphate. Phosphomannomutase (Pmm2)
  converts mannose 6-phosphate to mannose 1-phosphate, and GDP-mannose
  pyrophosphorylase, formed by the catalytic subunit Gmppb and the regulatory
  subunit Gmppa, condenses mannose 1-phosphate with GTP to make GDP-mannose.
summary: >-
  Hexose phosphorylation and isomerization (Hex-A, Hex-C, Pgi, Mpi), Pmm2 and
  the Gmppa-Gmppb pyrophosphorylase convert hexoses to GDP-mannose.
concepts:
  - {id: GO:0009298, label: GDP-mannose biosynthetic process}
cellular_components:
  - {id: GO:0005829, label: cytosol}
parts:
  - id: hexose_phosphorylation
    label: Hexose phosphorylation
    role: glucose or mannose to hexose 6-phosphate
    genes: [Hex-A, Hex-C]
    complex: false
    function: {id: GO:0004396, label: hexokinase activity}
  - id: glucose_phosphate_isomerization
    label: Glucose 6-phosphate isomerization
    role: glucose 6-phosphate to fructose 6-phosphate
    genes: [Pgi]
    function: {id: GO:0004347, label: glucose-6-phosphate isomerase activity}
  - id: mannose_phosphate_isomerization
    label: Mannose 6-phosphate isomerization
    role: fructose 6-phosphate to mannose 6-phosphate
    genes: [Mpi]
    function: {id: GO:0004476, label: mannose-6-phosphate isomerase activity}
  - id: phosphomannomutation
    label: Phosphomannomutation
    role: mannose 6-phosphate to mannose 1-phosphate
    genes: [Pmm2]
    function: {id: GO:0004615, label: phosphomannomutase activity}
  - id: gdp_mannose_pyrophosphorylase
    label: GDP-mannose pyrophosphorylase
    role: mannose 1-phosphate + GTP to GDP-mannose
    description: >-
      Gmppb is the catalytic subunit; Gmppa is a catalytically inactive
      regulatory subunit.
    genes: [Gmppb, Gmppa]
    module_type: PROTEIN_COMPLEX
    complex: true
    complex_term: {id: GO:0120508, label: GDP-mannose pyrophosphorylase complex}
    unit_functions:
      Gmppb: {id: GO:0004475, label: mannose-1-phosphate guanylyltransferase (GTP) activity}
    roles:
      Gmppb: catalytic subunit
      Gmppa: regulatory subunit
connections:
  - source: hexose_phosphorylation
    target: glucose_phosphate_isomerization
    connection_type: PRECEDES
    description: Glucose 6-phosphate from hexokinase is isomerized by Pgi.
  - source: glucose_phosphate_isomerization
    target: mannose_phosphate_isomerization
    connection_type: PRECEDES
    description: Fructose 6-phosphate is converted to mannose 6-phosphate by Mpi.
  - source: hexose_phosphorylation
    target: phosphomannomutation
    connection_type: PRECEDES
    description: Mannose 6-phosphate made directly from mannose by hexokinase enters at Pmm2.
  - source: mannose_phosphate_isomerization
    target: phosphomannomutation
    connection_type: PRECEDES
    description: Mannose 6-phosphate is converted to mannose 1-phosphate by Pmm2.
  - source: phosphomannomutation
    target: gdp_mannose_pyrophosphorylase
    connection_type: PRECEDES
    description: Mannose 1-phosphate is condensed with GTP to GDP-mannose.
notes: >-
  Boundary. The module covers the seven FlyBase members. Pgi and the
  hexokinases are shared with glycolysis and act in many pathways; they are
  included because FlyBase places them in this group. The Gmppa-Gmppb
  pyrophosphorylase is modelled as one complex. Use of GDP-mannose for
  GDP-fucose synthesis is modelled in the GDP-fucose biosynthesis module.
group: MANGPG