module: dmel_udp_glucuronate_xylose_biosynthesis
title: UDP-glucuronate and UDP-xylose biosynthesis in Drosophila melanogaster
label: UDP-glucuronate and UDP-xylose biosynthesis
module_type: METABOLIC_PATHWAY
description: >-
  UDP-glucuronic acid and UDP-xylose are the sugar donors for proteoglycan
  glycosaminoglycan chains and for other glucuronidated and xylosylated
  molecules. UDP-glucose pyrophosphorylase (Ugp) makes UDP-glucose from
  glucose-1-phosphate and UTP, and UDP-glucose 6-dehydrogenase (Sugarless, sgl)
  oxidises it to UDP-glucuronic acid in the cytosol. The nucleotide-sugar
  transporter Fringe connection (frc) imports UDP-glucuronic acid and other UDP
  sugars into the ER and Golgi lumen, where UDP-glucuronic acid decarboxylase
  (Uxs) converts UDP-glucuronic acid to UDP-xylose. Sugarless and Fringe
  connection were identified genetically through their requirement for Wingless
  and other heparan sulfate proteoglycan-dependent signalling.
summary: >-
  Synthesis of UDP-glucuronic acid and UDP-xylose from glucose-1-phosphate and
  their supply to the secretory pathway.
concepts:
  - {id: GO:0006065, label: UDP-glucuronate biosynthetic process}
  - {id: GO:0033320, label: UDP-D-xylose biosynthetic process}
parts:
  - id: udp_glucose_synthesis
    label: UDP-glucose synthesis
    role: step 1, glucose-1-phosphate and UTP to UDP-glucose
    module_type: REACTION
    genes: [Ugp]
    function: {id: GO:0003983, label: UTP:glucose-1-phosphate uridylyltransferase activity}
  - id: udp_glucose_oxidation
    label: UDP-glucose oxidation
    role: step 2, UDP-glucose to UDP-glucuronic acid
    module_type: REACTION
    genes: [sgl]
    function: {id: GO:0003979, label: UDP-glucose 6-dehydrogenase activity}
  - id: udp_sugar_import
    label: UDP-sugar import into the secretory pathway
    role: step 3, transport of UDP-glucuronic acid into the ER and Golgi
    module_type: TRANSPORT_STEP
    genes: [frc]
    function: {id: GO:0005461, label: UDP-glucuronate transmembrane transporter activity}
  - id: udp_glucuronate_decarboxylation
    label: UDP-glucuronic acid decarboxylation
    role: step 4, UDP-glucuronic acid to UDP-xylose
    module_type: REACTION
    genes: [Uxs]
    function: {id: GO:0048040, label: UDP-glucuronate decarboxylase activity}
connections:
  - source: udp_glucose_synthesis
    target: udp_glucose_oxidation
    connection_type: PRECEDES
    description: UDP-glucose is oxidised by Sugarless.
  - source: udp_glucose_oxidation
    target: udp_sugar_import
    connection_type: PRECEDES
    description: Cytosolic UDP-glucuronic acid is imported by Fringe connection.
  - source: udp_sugar_import
    target: udp_glucuronate_decarboxylation
    connection_type: PRECEDES
    description: Lumenal UDP-glucuronic acid is decarboxylated to UDP-xylose.
notes: >-
  Boundary. The module ends with the nucleotide sugars; their use by
  glycosyltransferases (for example xylosyltransferase Oxt and the
  glucuronyltransferases) is in dmel_glycosaminoglycan_biosynthesis and other
  glycosylation modules. Ugp also supplies UDP-glucose for glycogen and
  trehalose synthesis. frc and sgl are in both FlyBase groups and appear once.
  Fringe connection transports several UDP sugars (UDP-glucuronic acid,
  UDP-GlcNAc, UDP-xylose and others); the annoton gives the UDP-glucuronate
  transport activity relevant here. Placing Uxs after import assumes a lumenal
  enzyme, as for its mammalian ortholog UXS1; the topology of fly Uxs has not
  been determined.