module: dmel_cuticle_tanning_pigmentation
title: Cuticle tanning and pigmentation in Drosophila melanogaster
label: Cuticle tanning and pigmentation
module_type: METABOLIC_PATHWAY
description: >-
  After each molt and at eclosion, the insect cuticle is hardened
  (sclerotized) and pigmented using dopamine made by tyrosine hydroxylase
  (Pale) and DOPA decarboxylase. Dopamine is used in three branches. Arylalkylamine
  N-acetyltransferase (Speck, Aanat1) acetylates it to N-acetyldopamine (NADA),
  the precursor of colourless sclerotin. Ebony conjugates dopamine with
  beta-alanine to N-beta-alanyldopamine (NBAD), the precursor of yellow-tan
  sclerotin, and Tan hydrolyses NBAD back to dopamine, so the Ebony-Tan balance
  sets cuticle colour. Oxidation of dopamine and DOPA by phenoloxidases yields
  quinones and chromes that polymerize into black and brown melanins; the
  Yellow family proteins Yellow-f and Yellow-f2 convert dopachrome and
  Yellow-h converts dopaminechrome, and Yellow itself is needed for black
  melanin. Beta-alanine for NBAD comes from decarboxylation of aspartate by
  Black (Adc) and from uracil degradation through dihydropyrimidine
  dehydrogenase, dihydropyrimidinase and beta-ureidopropionase.
summary: >-
  Dopamine-derived NADA, NBAD and melanin pathways, with beta-alanine supply,
  that sclerotize and pigment the cuticle.
concepts:
  - {id: GO:0048067, label: cuticle pigmentation}
  - {id: GO:0007593, label: chitin-based cuticle sclerotization}
parts:
  - id: beta_alanine_supply
    label: Beta-alanine supply
    role: beta-alanine production for NBAD synthesis
    processes:
      - {id: GO:0019483, label: beta-alanine biosynthetic process}
    parts:
      - id: aspartate_decarboxylation
        label: Aspartate decarboxylation
        role: aspartate to beta-alanine
        genes: [Adc]
        function: {id: GO:0004068, label: aspartate 1-decarboxylase activity}
      - id: uracil_reduction
        label: Uracil reduction
        role: uracil to dihydrouracil
        genes: [su(r)]
        function: {id: GO:0017113, label: dihydropyrimidine dehydrogenase (NADP+) activity}
      - id: dihydrouracil_hydrolysis
        label: Dihydrouracil ring opening
        role: dihydrouracil to N-carbamoyl-beta-alanine
        genes: [Crmp]
        function: {id: GO:0004157, label: dihydropyrimidinase activity}
      - id: ureidopropionate_hydrolysis
        label: N-carbamoyl-beta-alanine hydrolysis
        role: N-carbamoyl-beta-alanine to beta-alanine
        genes: [pyd3]
        function: {id: GO:0003837, label: beta-ureidopropionase activity}
    connections:
      - source: uracil_reduction
        target: dihydrouracil_hydrolysis
        connection_type: PRECEDES
        description: Dihydrouracil is hydrolysed by dihydropyrimidinase.
      - source: dihydrouracil_hydrolysis
        target: ureidopropionate_hydrolysis
        connection_type: PRECEDES
        description: N-carbamoyl-beta-alanine is hydrolysed to beta-alanine.
  - id: nbad_synthesis
    label: NBAD synthesis
    role: dopamine + beta-alanine to N-beta-alanyldopamine
    genes: [e]
    function: {id: GO:0003833, label: beta-alanyl amine synthase activity}
  - id: nbad_hydrolysis
    label: NBAD hydrolysis
    role: N-beta-alanyldopamine to dopamine + beta-alanine
    genes: [t]
    function: {id: GO:0003832, label: beta-alanyl-dopamine hydrolase activity}
  - id: nada_synthesis
    label: NADA synthesis
    role: dopamine to N-acetyldopamine
    genes: [speck]
    function: {id: GO:0004059, label: aralkylamine N-acetyltransferase activity}
  - id: melanin_formation
    label: Melanin formation
    role: conversion of oxidized catecholamines into melanin
    description: >-
      Yellow-f and Yellow-f2 convert dopachrome and Yellow-h converts
      dopaminechrome; Yellow is required for black melanin but its biochemical
      activity is not established.
    genes: [yellow-f, yellow-f2, yellow-h, y]
    complex: false
    unit_functions:
      yellow-f: {id: GO:0004167, label: dopachrome isomerase activity}
      yellow-f2: {id: GO:0004167, label: dopachrome isomerase activity}
      yellow-h: {id: GO:0106417, label: dopaminechrome tautomerase activity}
    processes:
      - {id: GO:0042438, label: melanin biosynthetic process}
  - id: straw
    label: Straw
    role: pigmentation factor of unknown activity
    description: >-
      FlyBase places Straw in the melanin, NADA and NBAD branches; its
      biochemical activity is unknown.
    genes: [stw]
connections:
  - source: beta_alanine_supply
    target: nbad_synthesis
    connection_type: PROVIDES_INPUT_FOR
    description: Beta-alanine is the second substrate of Ebony.
  - source: nbad_synthesis
    target: nbad_hydrolysis
    connection_type: PROVIDES_INPUT_FOR
    description: NBAD made by Ebony can be hydrolysed back to dopamine by Tan.
  - source: nbad_hydrolysis
    target: melanin_formation
    connection_type: PROVIDES_INPUT_FOR
    description: Dopamine released by Tan feeds melanin formation.
knowledge_gaps:
  - gap_statement: >-
      The biochemical activities of Yellow and Straw in melanin formation and
      cuticle tanning are unknown.
    boundary: Melanin branch of cuticle pigmentation.
    gap_kind: [BIOLOGY]
notes: >-
  Boundary. The module realizes the FlyBase pigment biosynthesis group without
  its ommochrome subgroup (OMMOBI), which is modelled in a separate ommochrome
  module, together with the beta-alanine biosynthesis group. Dopamine synthesis
  by Pale and Ddc is upstream context modelled in the catecholamine
  biosynthesis module, and the phenoloxidase Laccase 2 and the cuticle proteins
  that are cross-linked are not FlyBase members and are not parts. Yellow (y)
  is not a member of the FlyBase pigment biosynthesis group; it was added to
  the melanin part because it is required for black melanin. Ebony and Tan also
  act in histamine recycling (histamine metabolism module). Uracil-derived
  beta-alanine steps are assigned by orthology to the pyrimidine reductive
  degradation enzymes.
groups: [MELABI, DYNADAB, DYNBADB, BALABIO]