module: dmel_methionine_salvage
title: L-methionine salvage pathway in Drosophila melanogaster
label: Methionine salvage pathway
module_type: METABOLIC_PATHWAY
description: >-
  The methionine salvage pathway recycles the methylthio group of
  5'-methylthioadenosine (MTA), a by-product of polyamine synthesis, back into
  methionine. MTA phosphorylase (Mtap) cleaves MTA to adenine and
  5-methylthioribose-1-phosphate, which is isomerised to
  methylthioribulose-1-phosphate (Mri1) and dehydrated to a diketo phosphate
  (CG11134). The bifunctional enolase-phosphatase Enoph converts this to
  acireductone, which acireductone dioxygenase (Adi1) oxidises to
  4-methylthio-2-oxobutanoate. A final transamination regenerates methionine.
  As in other animals, the pathway in flies lacks the methylthioribose kinase
  step used by bacteria and plants, because MTA is cleaved phosphorolytically.
summary: >-
  Five-enzyme pathway that converts 5'-methylthioadenosine back to the
  methionine precursor 4-methylthio-2-oxobutanoate.
concepts:
  - {id: GO:0071267, label: L-methionine salvage}
parts:
  - id: mta_phosphorolysis
    label: 5'-methylthioadenosine phosphorolysis
    role: step 1, MTA to methylthioribose-1-phosphate
    module_type: REACTION
    genes: [Mtap]
    function: {id: GO:0017061, label: S-methyl-5-thioadenosine phosphorylase activity}
  - id: mtr1p_isomerization
    label: Methylthioribose-1-phosphate isomerization
    role: step 2, isomerization to methylthioribulose-1-phosphate
    module_type: REACTION
    genes: [Mri1]
    function: {id: GO:0046523, label: S-methyl-5-thioribose-1-phosphate isomerase activity}
  - id: mtru1p_dehydration
    label: Methylthioribulose-1-phosphate dehydration
    role: step 3, dehydration to the diketo phosphate
    module_type: REACTION
    genes: [CG11134]
    function: {id: GO:0046570, label: methylthioribulose 1-phosphate dehydratase activity}
  - id: enolase_phosphatase
    label: Enolization and dephosphorylation to acireductone
    role: step 4, diketo phosphate to acireductone
    module_type: REACTION
    genes: [Enoph]
    function: {id: GO:0043874, label: acireductone synthase activity}
  - id: acireductone_dioxygenation
    label: Acireductone dioxygenation
    role: step 5, acireductone to 4-methylthio-2-oxobutanoate
    module_type: REACTION
    genes: [Adi1]
    function: {id: GO:0010309, label: "acireductone dioxygenase [iron(II)-requiring] activity"}
connections:
  - {source: mta_phosphorolysis, target: mtr1p_isomerization, connection_type: PRECEDES, description: 5-methylthioribose-1-phosphate is the substrate of the isomerase.}
  - {source: mtr1p_isomerization, target: mtru1p_dehydration, connection_type: PRECEDES, description: Methylthioribulose-1-phosphate is dehydrated.}
  - {source: mtru1p_dehydration, target: enolase_phosphatase, connection_type: PRECEDES, description: The diketo phosphate is enolized and dephosphorylated to acireductone.}
  - {source: enolase_phosphatase, target: acireductone_dioxygenation, connection_type: PRECEDES, description: Acireductone is oxidised by Adi1.}
notes: >-
  Boundary. The final transamination of 4-methylthio-2-oxobutanoate to
  methionine is carried out by broad-specificity aminotransferases that FlyBase
  does not include in this group, so it is not modelled. Adi1 is given the
  iron-dependent dioxygenase activity, which yields the methionine precursor;
  the nickel-dependent activity that yields methylthiopropionate is a
  side reaction. Molecular functions follow orthology to the characterized
  enzymes of other organisms; except for Mtap, the fly enzymes have not been
  assayed directly.