module: dmel_ommochrome_biosynthesis
title: Tryptophan catabolism to ommochrome pigments in Drosophila melanogaster
label: Ommochrome biosynthesis
module_type: METABOLIC_PATHWAY
description: >-
  The brown ommochrome eye pigment xanthommatin is made from tryptophan through
  the kynurenine pathway, which in insects is also the main route of tryptophan
  catabolism. Tryptophan 2,3-dioxygenase (vermilion) opens the indole ring to
  give N-formylkynurenine, kynurenine formamidase (Kfase) releases kynurenine,
  and kynurenine 3-monooxygenase (cinnabar) hydroxylates it to
  3-hydroxykynurenine. 3-Hydroxykynurenine is imported into pigment granules of
  the eye and other tissues by the White-Scarlet ABC transporter, where it is
  condensed to xanthommatin; this last step requires the heme peroxidase
  Cardinal. Mutations in v, cn, w, st and cd give the classic eye-colour
  phenotypes that lack or reduce brown pigment.
summary: >-
  Kynurenine pathway that converts tryptophan to 3-hydroxykynurenine and, in
  pigment granules, to the ommochrome xanthommatin.
concepts:
  - {id: GO:0006727, label: ommochrome biosynthetic process}
  - {id: GO:0006569, label: L-tryptophan catabolic process}
cellular_components:
  - {id: GO:0048770, label: pigment granule}
parts:
  - id: tryptophan_dioxygenation
    label: Tryptophan 2,3-dioxygenation
    role: step 1, tryptophan to N-formylkynurenine
    module_type: REACTION
    genes: [v]
    function: {id: GO:0004833, label: "L-tryptophan 2,3-dioxygenase activity"}
  - id: formylkynurenine_hydrolysis
    label: N-formylkynurenine hydrolysis
    role: step 2, N-formylkynurenine to kynurenine
    module_type: REACTION
    genes: [Kfase]
    function: {id: GO:0004061, label: arylformamidase activity}
  - id: kynurenine_hydroxylation
    label: Kynurenine 3-hydroxylation
    role: step 3, kynurenine to 3-hydroxykynurenine
    module_type: REACTION
    genes: [cn]
    function: {id: GO:0004502, label: kynurenine 3-monooxygenase activity}
  - id: granule_import
    label: White-Scarlet transporter
    role: step 4, import of 3-hydroxykynurenine into pigment granules
    module_type: PROTEIN_COMPLEX
    complex: true
    genes: [w, st]
    complex_label: White-Scarlet ABC transporter
  - id: xanthommatin_formation
    label: Xanthommatin formation
    role: step 5, condensation of 3-hydroxykynurenine to xanthommatin
    module_type: REACTION
    genes: [cd]
connections:
  - source: tryptophan_dioxygenation
    target: formylkynurenine_hydrolysis
    connection_type: PRECEDES
    description: N-formylkynurenine is deformylated to kynurenine.
  - source: formylkynurenine_hydrolysis
    target: kynurenine_hydroxylation
    connection_type: PRECEDES
    description: Kynurenine is hydroxylated by Cinnabar.
  - source: kynurenine_hydroxylation
    target: granule_import
    connection_type: PRECEDES
    description: 3-Hydroxykynurenine is taken up into pigment granules.
  - source: granule_import
    target: xanthommatin_formation
    connection_type: PRECEDES
    description: 3-Hydroxykynurenine in the granule is converted to xanthommatin.
notes: >-
  Boundary. The module joins the FlyBase tryptophan catabolism and ommochrome
  pigment groups, which share v, Kfase and cn. White also pairs with Brown to
  import pteridine (drosopterin) precursors; that heterodimer belongs to
  pteridine pigment synthesis and is not modelled here. No molecular function is
  given to the White-Scarlet transporter, since the exact transported substrate
  has been inferred from genetics rather than transport assays, or to Cardinal,
  which has peroxidase activity by homology but whose precise chemistry in
  xanthommatin synthesis is not settled. Kynurenic acid and other kynurenine
  side branches are not part of this module.
knowledge_gaps:
  - gap_statement: >-
      The enzymatic mechanism of the final oxidative condensation of
      3-hydroxykynurenine to xanthommatin, including whether Cardinal catalyses
      it directly, is not established.
    boundary: Final step of xanthommatin synthesis in pigment granules.
    gap_kind: [BIOLOGY]