module: dmel_mitochondrial_fatty_acid_synthesis
title: Mitochondrial type II fatty acid synthesis in Drosophila melanogaster
label: Mitochondrial fatty acid synthesis
module_type: METABOLIC_PATHWAY
description: >-
  Mitochondria carry their own type II fatty acid synthesis (mtFAS) system, in
  which separate enzymes act on acyl chains attached to the mitochondrial acyl
  carrier protein (ND-ACP). Malonyl groups are loaded onto ACP by the malonyl
  transacylase (beg), condensed by a beta-ketoacyl-ACP synthase (CG12170),
  reduced by a 3-ketoacyl-ACP reductase, dehydrated and then reduced by the
  enoyl-ACP reductase Mecr. The main product, octanoyl-ACP, is the precursor of
  lipoic acid; acylated ACP also binds and supports assembly of respiratory
  complex I and the iron-sulfur cluster assembly machinery.
summary: >-
  Acyl carrier protein-based fatty acid synthesis in mitochondria that supplies
  octanoyl chains for lipoic acid synthesis.
concepts:
  - {id: GO:0006633, label: fatty acid biosynthetic process}
cellular_components:
  - {id: GO:0005759, label: mitochondrial matrix}
parts:
  - id: malonyl_coa_supply
    label: Malonyl-CoA supply
    role: carboxylation of acetyl-CoA to malonyl-CoA
    module_type: REACTION
    genes: [Acc]
    function: {id: GO:0003989, label: acetyl-CoA carboxylase activity}
  - id: acyl_carrier
    label: Mitochondrial acyl carrier protein
    role: carrier of the growing acyl chain
    genes: [ND-ACP]
    function: {id: GO:0000036, label: acyl carrier activity}
  - id: malonyl_transacylation
    label: Malonyl transfer to ACP
    role: step 1, malonyl-CoA to malonyl-ACP
    module_type: REACTION
    genes: [beg]
    function: {id: GO:0004314, label: "[acyl-carrier-protein] S-malonyltransferase activity"}
  - id: ketoacyl_condensation
    label: Condensation to 3-oxoacyl-ACP
    role: step 2, Claisen condensation
    module_type: REACTION
    genes: [CG12170]
    function: {id: GO:0004315, label: "3-oxoacyl-[acyl-carrier-protein] synthase activity"}
  - id: ketoacyl_reduction
    label: Reduction of 3-oxoacyl-ACP
    role: step 3, 3-ketoacyl-ACP reduction
    module_type: REACTION
    genes: [CG3603]
  - id: enoyl_reduction
    label: Reduction of trans-2-enoyl-ACP
    role: step 5, enoyl-ACP reduction
    module_type: REACTION
    genes: [Mecr]
    function: {id: GO:0141148, label: "enoyl-[acyl-carrier-protein] reductase (NADPH) activity"}
connections:
  - {source: malonyl_coa_supply, target: malonyl_transacylation, connection_type: PROVIDES_INPUT_FOR, description: Malonyl-CoA is the donor for malonyl-ACP.}
  - {source: acyl_carrier, target: malonyl_transacylation, connection_type: PROVIDES_INPUT_FOR, description: ND-ACP is the acceptor of the malonyl group and carries the chain through each cycle.}
  - {source: malonyl_transacylation, target: ketoacyl_condensation, connection_type: PRECEDES, description: Malonyl-ACP is condensed with the acyl primer.}
  - {source: ketoacyl_condensation, target: ketoacyl_reduction, connection_type: PRECEDES, description: The 3-oxoacyl-ACP is reduced to 3-hydroxyacyl-ACP.}
  - {source: ketoacyl_reduction, target: enoyl_reduction, connection_type: PRECEDES, description: "After dehydration, the trans-2-enoyl-ACP is reduced by Mecr."}
notes: >-
  Boundary and caveats. The 3-hydroxyacyl-ACP dehydratase step (step 4; HTD2 in
  mammals) is not in the FlyBase group and is not modelled, so the connection
  from ketoacyl reduction to enoyl reduction spans it. Acc is a FlyBase member
  but is best known as the cytosolic acetyl-CoA carboxylase; whether a fly Acc
  isoform supplies malonyl-CoA inside mitochondria is not established (mammals
  use ACSF3 for intramitochondrial malonyl-CoA), so it is modelled as the
  malonyl-CoA supply step without a location claim. CG3603 is assigned to the
  ketoreductase step by its membership in the FlyBase group; in mammals this
  step is performed by an HSD17B8-CBR4 heterotetramer and the fly assignment is
  only by sequence similarity, so no molecular function is given. ND-ACP is also
  a subunit of respiratory complex I and part of the iron-sulfur cluster
  assembly complex (module dmel_iron_sulfur_cluster_assembly). Other molecular
  functions follow orthology and have not been assayed in flies.
knowledge_gaps:
  - gap_statement: >-
      Which fly proteins perform the 3-ketoacyl-ACP reductase and
      3-hydroxyacyl-ACP dehydratase steps inside mitochondria, and how
      malonyl-CoA is generated in the fly mitochondrial matrix, have not been
      determined experimentally.
    boundary: Mitochondrial type II fatty acid synthesis steps 3 and 4 and malonyl-CoA supply.
    gap_kind: [BIOLOGY]