module: dmel_citrate_malate_shuttle
title: Citrate-malate shuttle in Drosophila melanogaster
label: Citrate-malate shuttle
module_type: METABOLIC_PATHWAY
description: >-
  The citrate-malate shuttle moves acetyl units from mitochondria to the
  cytosol for fatty acid and sterol synthesis and for histone acetylation.
  Citrate made in the mitochondrial matrix is exported by the mitochondrial
  citrate carrier, encoded in Drosophila by scheggia (sea), in exchange for
  malate. In the cytosol ATP-citrate lyase (Acly) cleaves citrate into
  acetyl-CoA and oxaloacetate, and cytosolic malate dehydrogenase (Mdh1)
  reduces the oxaloacetate to malate, which can return to the mitochondria
  through the citrate carrier or be decarboxylated by malic enzyme.
summary: >-
  Mitochondrial citrate export by Sea, cytosolic citrate cleavage by Acly and
  oxaloacetate reduction by Mdh1.
concepts:
  - {id: GO:0006843, label: mitochondrial citrate transmembrane transport}
parts:
  - id: citrate_export
    label: Mitochondrial citrate export
    role: citrate export from mitochondria in exchange for malate
    genes: [sea]
    function: {id: GO:0015137, label: citrate transmembrane transporter activity}
    locations:
      - {id: GO:0005743, label: mitochondrial inner membrane}
  - id: citrate_cleavage
    label: Cytosolic citrate cleavage
    role: citrate to acetyl-CoA + oxaloacetate
    genes: [Acly]
    function: {id: GO:0003878, label: ATP citrate synthase activity}
    locations:
      - {id: GO:0005829, label: cytosol}
  - id: oxaloacetate_reduction
    label: Oxaloacetate reduction
    role: oxaloacetate to malate
    genes: [Mdh1]
    function: {id: GO:0030060, label: L-malate dehydrogenase (NAD+) activity}
    locations:
      - {id: GO:0005829, label: cytosol}
connections:
  - source: citrate_export
    target: citrate_cleavage
    connection_type: PRECEDES
    description: Exported citrate is cleaved by ATP-citrate lyase in the cytosol.
  - source: citrate_cleavage
    target: oxaloacetate_reduction
    connection_type: PRECEDES
    description: Oxaloacetate from citrate cleavage is reduced to malate by Mdh1.
  - source: oxaloacetate_reduction
    target: citrate_export
    connection_type: PROVIDES_INPUT_FOR
    description: Cytosolic malate is the counter-substrate for citrate export.
notes: >-
  Boundary. The module covers the three FlyBase members. Mitochondrial citrate
  synthase and the cytosolic NADP-malic enzymes (see the cytosolic NADPH
  regeneration module) are adjacent steps and not parts. The citrate carrier
  function of Sea and the enzyme functions are assigned by orthology to the
  conserved mammalian proteins. The module is grounded to mitochondrial citrate
  transmembrane transport because the newer GO term citrate-malate shuttle
  (GO:7770108) is not yet in the ontology release used for validation; it
  should replace the concept once available.
group: CIMALSH