module: dmel_cytosolic_nadph_regeneration
title: Cytosolic NADPH regeneration in Drosophila melanogaster
label: Cytosolic NADPH regeneration
module_type: METABOLIC_PATHWAY
description: >-
  NADPH supplies reducing power for fatty acid synthesis and for antioxidant
  systems such as glutathione and thioredoxin reduction. In Drosophila, as in
  other animals, it is regenerated outside mitochondria by three sets of
  NADP-dependent dehydrogenases. The oxidative branch of the pentose phosphate
  pathway produces two NADPH per glucose 6-phosphate through
  glucose-6-phosphate dehydrogenase (G6pd, Zw) and 6-phosphogluconate
  dehydrogenase (Pgd). NADP-dependent isocitrate dehydrogenase (Idh) oxidizes
  isocitrate to 2-oxoglutarate, and NADP-dependent malic enzyme (Men)
  decarboxylates malate to pyruvate, each reducing NADP+. Studies of fly
  mutants and allozyme variants link these enzymes to lipid accumulation.
summary: >-
  NADPH regeneration by the oxidative pentose phosphate pathway (G6pd, Pgd),
  NADP-isocitrate dehydrogenase (Idh) and malic enzymes (Men, Men-b).
concepts:
  - {id: GO:0006740, label: NADPH regeneration}
parts:
  - id: oxidative_pentose_phosphate
    label: Oxidative pentose phosphate pathway
    role: glucose 6-phosphate to ribulose 5-phosphate with two NADPH
    parts:
      - id: g6p_dehydrogenation
        label: Glucose 6-phosphate dehydrogenation
        role: glucose 6-phosphate to 6-phosphogluconolactone
        genes: [G6pd]
        function: {id: GO:0004345, label: glucose-6-phosphate dehydrogenase activity}
      - id: phosphogluconate_decarboxylation
        label: 6-Phosphogluconate oxidative decarboxylation
        role: 6-phosphogluconate to ribulose 5-phosphate
        genes: [Pgd]
        function: {id: GO:0004616, label: phosphogluconate dehydrogenase (decarboxylating) activity}
    connections:
      - source: g6p_dehydrogenation
        target: phosphogluconate_decarboxylation
        connection_type: PRECEDES
        description: >-
          6-phosphogluconate, formed from the G6pd product by lactonase, is
          oxidized by Pgd.
  - id: isocitrate_oxidation
    label: NADP-isocitrate oxidation
    role: isocitrate to 2-oxoglutarate with NADPH
    genes: [Idh]
    function: {id: GO:0004450, label: isocitrate dehydrogenase (NADP+) activity}
  - id: malate_decarboxylation
    label: NADP-malic enzyme decarboxylation
    role: malate to pyruvate with NADPH
    description: >-
      Men is the main NADP-malic enzyme; Men-b is a paralog whose activity has
      not been characterized.
    genes: [Men, Men-b]
    complex: false
    unit_functions:
      Men: {id: GO:0004473, label: malate dehydrogenase (decarboxylating) (NADP+) activity}
notes: >-
  Boundary. The module covers the five FlyBase NADPH regeneration enzymes. The
  three parts are parallel sources of NADPH and are not linked by connections.
  The 6-phosphogluconolactonase step between G6pd and Pgd is not a FlyBase
  member and is not modelled. Mitochondrial NADPH sources (for example
  nicotinamide nucleotide transhydrogenase) are outside the module.
group: NADPHRE