methylglyoxal degradation I

MetaCyc:PWY-5386

The complete three-reaction glutathione-dependent route from methylglyoxal to pyruvate represented by MetaCyc PWY-5386 and PathBank SMP0002125, curated for the E. coli K-12 protein core. GloA acts as a homodimer on the spontaneously formed methylglyoxal-glutathione hemithioacetal; the source net reaction includes that nonenzymatic condensation. Monomeric GloB hydrolyzes (R)-S-lactoylglutathione, regenerating glutathione and releasing D-(R)-lactate. FAD-dependent membrane-associated Dld oxidizes D-lactate to pyruvate while reducing a quinone. Exact Rhea quinone/quinol classes are retained without asserting ubiquinone-6 specificity; ubiquinone-8 supports reconstituted E. coli respiration. The native PathBank L-lactate identity and oxidized-glutathione cross-reference are rejected. Pathway-level flux evidence comes from MG1655-derived SIJ488 strains with engineered glycolytic deletions grown on glycerol, not unrestricted wild-type flux. The older MetaCyc description calls the D-lactate fate likely; the 2022 deletion study supports this branch in its tested context. The GloB branch does not exclude accessory GloC activity. Ni activates GloA whereas Zn activates GloB; published GloA metal occupancies differ and are retained in the cofactor evidence. Upstream methylglyoxal synthesis, alternative glutathione-independent routes, Kef regulation and downstream respiratory-chain reactions are outside this pathway.

Pathway type
detoxification
Organism scope

Read the source YAML

Pathway network

21 nodes · 25 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Pathway network: methylglyoxal degradation I 21 nodes · 25 asserted directed edges. Every arrow links to its evidence table row; nodes link to their component details. Isolated declared components are retained. CHEBI:17158 — consumes → RHEA:19071; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:19069consumes CHEBI:57925 — consumes → RHEA:19071; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:19069consumes RHEA:19071 — produces → CHEBI:57474; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:19069produces CHEBI:57474 — consumes → RHEA:25246; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:25245consumes CHEBI:15377 — consumes → RHEA:25246; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:25245consumes RHEA:25246 — produces → CHEBI:16004; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:25245produces RHEA:25246 — produces → CHEBI:57925; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:25245produces RHEA:25246 — produces → CHEBI:15378; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:25245produces CHEBI:16004 — consumes → RHEA:51469; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:51468consumes CHEBI:132124 — consumes → RHEA:51469; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:51468consumes RHEA:51469 — produces → CHEBI:24646; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:51468produces RHEA:51469 — produces → CHEBI:15361; Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.; Evidence: RHEA:51468produces UniProtKB:P0AC81 — part_of → MetaCyc:GLYOXI-CPLX; Two GloA chains form the homodimer; subunit membership does not assert that an isolated chain catalyzes the net reaction.; Evidence: MetaCyc:GLYOXI-CPLX, MetaCyc:GLYOXI-MONOMER, PMID:9628737part of MetaCyc:GLYOXI-CPLX — catalyzes → RHEA:19071; GloA isomerizes the hemithioacetal formed spontaneously from methylglyoxal and glutathione. The Rhea net equation folds the preceding spontaneous equilibrium into the conversion; it is not evidence that GloA catalyzes initial condensation.; Evidence: MetaCyc:GLYOXI-CPLX, UniProtKB:P0AC81, RHEA:19069, PathBank:SMP0002125catalyzes UniProtKB:P0AC84 — catalyzes → RHEA:25246; Monomeric GloB hydrolyzes the R-specific thioester. This is the source map’s GloB branch; GloC provides an experimentally supported accessory isoenzyme but is not required to invent an additional chemical step.; Evidence: UniProtKB:P0AC84, RHEA:25245, PMID:17196158, PathBank:SMP0002125, PMID:25670698catalyzes UniProtKB:P06149 — catalyzes → RHEA:51469; Respiratory Dld oxidizes D-(R)-lactate using enzyme-bound FAD and a quinone acceptor. The generic Rhea class is faithful to current annotation; no UQ6 specificity, NAD dependence or direct proton pumping by Dld is inferred. The inspected 1986 reconstitution used ubiquinone-8; its electron-transfer step was not electrogenic.; Evidence: UniProtKB:P06149, RHEA:51468, PathBank:SMP0002125, PMID:3013300catalyzes MetaCyc:GLYOXI-CPLX — has_cofactor → CHEBI:49786; Ni2+ activates E. coli GloA, whereas Zn2+ does not. Current annotation of the 2000 structures reports one Ni per subunit/two per dimer; the 1998 solution study reported one Ni per dimer. These are differing measurements, not a universal physiological occupancy. Co2+ and Cd2+ also activated protein-metal complexes in the structural study.; Evidence: UniProtKB:P0AC81, PMID:10913283, PMID:9628737has cofactor UniProtKB:P0AC84 — has_cofactor → CHEBI:29105; Current annotation reports two Zn2+ ions per GloB monomer. Mn2+ and Co2+ substitute in reconstitution experiments; this is not a claim of in vivo metal substitution. Neither GloA nickel dependence nor other organisms’ mixed metals are transferred to GloB.; Evidence: UniProtKB:P0AC84has cofactor UniProtKB:P06149 — has_cofactor → CHEBI:57692; FAD is bound to Dld and cycles redox state during turnover; it is not a freely consumed substrate in the net quinone reaction. The ChEBI charge state follows current UniProt grounding.; Evidence: UniProtKB:P06149, PMID:10944213has cofactor UniProtKB:P06149 — located_in → GO:0005886; Dld is a peripheral enzyme on the cytoplasmic side of the E. coli inner (plasma) membrane. The edge does not encode integral topology or a universal location for the whole pathway.; Evidence: UniProtKB:P06149, PMID:10944213located in RHEA:19071 — part_of → MetaCyc:PWY-5386; Native reaction membership plus an independently grounded selected Rhea direction. The Dld bridge uses matching catalyst and chemistry, not a fabricated exact-match cross-reference.; Evidence: MetaCyc:PWY-5386, MetaCyc:GLYOXI-RXN, RHEA:19069part of RHEA:25246 — part_of → MetaCyc:PWY-5386; Native reaction membership plus an independently grounded selected Rhea direction. The Dld bridge uses matching catalyst and chemistry, not a fabricated exact-match cross-reference.; Evidence: MetaCyc:PWY-5386, MetaCyc:GLYOXII-RXN, RHEA:25245part of RHEA:51469 — part_of → MetaCyc:PWY-5386; Native reaction membership plus an independently grounded selected Rhea direction. The Dld bridge uses matching catalyst and chemistry, not a fabricated exact-match cross-reference.; Evidence: MetaCyc:PWY-5386, MetaCyc:DLACTDEHYDROGFAD-RXN, UniProtKB:P06149, RHEA:51468part of RHEA:19071 — provides_input_for → RHEA:25246; The R-specific lactoylglutathione product is the GloB substrate; glutathione is regenerated by hydrolysis.; Evidence: RHEA:19069, RHEA:25245, UniProtKB:P0AC84provides input for RHEA:25246 — provides_input_for → RHEA:51469; GloB-derived D-lactate feeds Dld oxidation to pyruvate. The 2022 physiological test used MG1655-derived SIJ488 glycolysis mutants on glycerol; it does not prove identical basal flux in every K-12 condition or GloB exclusivity over GloC.; Evidence: RHEA:25245, RHEA:51468, PMID:37850128provides input for methylglyoxal; CHEBI:17158; Declared type: small_molecule small molecule methylglyoxal glutathionate(1-); CHEBI:57925; Declared type: small_molecule small molecule glutathionate(1-) (R)-S-lactoylglutathionate(1-); CHEBI:57474; Declared type: small_molecule small molecule (R)-S- lactoylglutathionate(1-) water; CHEBI:15377; Declared type: small_molecule small molecule water (R)-lactate; CHEBI:16004; Declared type: small_molecule small molecule (R)-lactate hydron; CHEBI:15378; Declared type: small_molecule small molecule hydron 1,4-benzoquinones; CHEBI:132124; Declared type: small_molecule small molecule 1,4-benzoquinones hydroquinones; CHEBI:24646; Declared type: small_molecule small molecule hydroquinones pyruvate; CHEBI:15361; Declared type: small_molecule small molecule pyruvate nickel(2+); CHEBI:49786; Declared type: cofactor cofactor nickel(2+) zinc(2+); CHEBI:29105; Declared type: cofactor cofactor zinc(2+) FAD(3-); CHEBI:57692; Declared type: cofactor cofactor FAD(3-) Lactoylglutathione lyase; UniProtKB:P0AC81; Declared type: protein protein Lactoylglutathione lyase Hydroxyacylglutathione hydrolase GloB; UniProtKB:P0AC84; Declared type: protein protein Hydroxyacylglutathione hydrolase GloB Quinone-dependent D-lactate dehydrogenase; UniProtKB:P06149; Declared type: protein protein Quinone-dependent D-lactate dehydrogenase glyoxalase I; MetaCyc:GLYOXI-CPLX; Declared type: complex complex glyoxalase I plasma membrane; GO:0005886; Declared type: cellular_component cellular component plasma membrane methylglyoxal + glutathione => (R)-S-lactoylglutathione; RHEA:19071; Declared type: molecular_activity; Source reaction direction: right_to_left molecular activity methylglyoxal + glutathione => (R)-S-lactoylglutathione (R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+); RHEA:25246; Declared type: molecular_activity; Source reaction direction: left_to_right molecular activity (R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+) (R)-lactate + a quinone => a quinol + pyruvate; RHEA:51469; Declared type: molecular_activity; Source reaction direction: left_to_right molecular activity (R)-lactate + a quinone => a quinol + pyruvate methylglyoxal degradation I; MetaCyc:PWY-5386; Declared type: pathway pathway methylglyoxal degradation I

Components and activities

Declared biological components and source reaction directions
NodeKind or roleSource direction
Escherichia coli K-12
NCBITaxon:83333		taxon
methylglyoxal
CHEBI:17158		small molecule
glutathionate(1-)
CHEBI:57925		small molecule
(R)-S-lactoylglutathionate(1-)
CHEBI:57474		small molecule
water
CHEBI:15377		small molecule
(R)-lactate
CHEBI:16004		small molecule
hydron
CHEBI:15378		small molecule
1,4-benzoquinones
CHEBI:132124		small molecule
hydroquinones
CHEBI:24646		small molecule
pyruvate
CHEBI:15361		small molecule
nickel(2+)
CHEBI:49786		cofactor
zinc(2+)
CHEBI:29105		cofactor
FAD(3-)
CHEBI:57692		cofactor
Lactoylglutathione lyase
UniProtKB:P0AC81		protein
Hydroxyacylglutathione hydrolase GloB
UniProtKB:P0AC84		protein
Quinone-dependent D-lactate dehydrogenase
UniProtKB:P06149		protein
glyoxalase I
MetaCyc:GLYOXI-CPLX		complex
plasma membrane
GO:0005886		cellular component
methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071		molecular activityright to left
(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246		molecular activityleft to right
(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469		molecular activityleft to right

Mechanistic edges

Mechanistic edges and their cited evidence
SubjectPredicate and descriptionObjectEvidence
methylglyoxal
CHEBI:17158		consumes

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071
  • RHEA:19069

    Source assertion: RHEA:19071 substrates contain CHEBI:17158 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/19071 rh:substrates; http://rdf.rhea-db.org/19069_R rh:contains1 http://rdf.rhea-db.org/Participant_19069_compound_4547; rh:compound/rh:chebi
glutathionate(1-)
CHEBI:57925		consumes

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071
  • RHEA:19069

    Source assertion: RHEA:19071 substrates contain CHEBI:57925 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/19071 rh:substrates; http://rdf.rhea-db.org/19069_R rh:contains1 http://rdf.rhea-db.org/Participant_19069_compound_4810; rh:compound/rh:chebi
methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071		produces

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

(R)-S-lactoylglutathionate(1-)
CHEBI:57474
  • RHEA:19069

    Source assertion: RHEA:19071 products contain CHEBI:57474 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/19071 rh:products; http://rdf.rhea-db.org/19069_L rh:contains1 http://rdf.rhea-db.org/Participant_19069_compound_1514; rh:compound/rh:chebi
(R)-S-lactoylglutathionate(1-)
CHEBI:57474		consumes

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246
  • RHEA:25245

    Source assertion: RHEA:25246 substrates contain CHEBI:57474 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/25246 rh:substrates; http://rdf.rhea-db.org/25245_L rh:contains1 http://rdf.rhea-db.org/Participant_25245_compound_1514; rh:compound/rh:chebi
water
CHEBI:15377		consumes

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246
  • RHEA:25245

    Source assertion: RHEA:25246 substrates contain CHEBI:15377 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/25246 rh:substrates; http://rdf.rhea-db.org/25245_L rh:contains1 http://rdf.rhea-db.org/Participant_25245_compound_1283; rh:compound/rh:chebi
(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246		produces

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

(R)-lactate
CHEBI:16004
  • RHEA:25245

    Source assertion: RHEA:25246 products contain CHEBI:16004 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/25246 rh:products; http://rdf.rhea-db.org/25245_R rh:contains1 http://rdf.rhea-db.org/Participant_25245_compound_2842; rh:compound/rh:chebi
(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246		produces

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

glutathionate(1-)
CHEBI:57925
  • RHEA:25245

    Source assertion: RHEA:25246 products contain CHEBI:57925 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/25246 rh:products; http://rdf.rhea-db.org/25245_R rh:contains1 http://rdf.rhea-db.org/Participant_25245_compound_4810; rh:compound/rh:chebi
(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246		produces

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

hydron
CHEBI:15378
  • RHEA:25245

    Source assertion: RHEA:25246 products contain CHEBI:15378 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/25246 rh:products; http://rdf.rhea-db.org/25245_R rh:contains1 http://rdf.rhea-db.org/Participant_25245_compound_3249; rh:compound/rh:chebi
(R)-lactate
CHEBI:16004		consumes

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469
  • RHEA:51468

    Source assertion: RHEA:51469 substrates contain CHEBI:16004 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/51469 rh:substrates; http://rdf.rhea-db.org/51468_L rh:contains1 http://rdf.rhea-db.org/Participant_51468_compound_2842; rh:compound/rh:chebi
1,4-benzoquinones
CHEBI:132124		consumes

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469
  • RHEA:51468

    Source assertion: RHEA:51469 substrates contain CHEBI:132124 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/51469 rh:substrates; http://rdf.rhea-db.org/51468_L rh:contains1 http://rdf.rhea-db.org/Participant_51468_compound_13027; rh:compound/rh:chebi
(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469		produces

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

hydroquinones
CHEBI:24646
  • RHEA:51468

    Source assertion: RHEA:51469 products contain CHEBI:24646 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/51469 rh:products; http://rdf.rhea-db.org/51468_R rh:contains1 http://rdf.rhea-db.org/Participant_51468_compound_13026; rh:compound/rh:chebi
(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469		produces

Coefficient 1 in the selected physiological direction. Charge and stereochemistry follow the exact Rhea chemical; quinone/quinol nodes are corresponding substituted chemical classes, not a chain-length-specific pair.

pyruvate
CHEBI:15361
  • RHEA:51468

    Source assertion: RHEA:51469 products contain CHEBI:15361 with coefficient 1.

    Source locationhttp://rdf.rhea-db.org/51469 rh:products; http://rdf.rhea-db.org/51468_R rh:contains1 http://rdf.rhea-db.org/Participant_51468_compound_3719; rh:compound/rh:chebi
Lactoylglutathione lyase
UniProtKB:P0AC81		part_of

Two GloA chains form the homodimer; subunit membership does not assert that an isolated chain catalyzes the net reaction.

glyoxalase I
MetaCyc:GLYOXI-CPLX
  • MetaCyc:GLYOXI-CPLX

    Source assertion: GLYOXI-CPLX contains GLYOXI-MONOMER with coefficient 2.

    Source location/ptools-xml/Protein[@frameid="GLYOXI-CPLX"]/component[Protein/@frameid="GLYOXI-MONOMER"]/coefficient
  • MetaCyc:GLYOXI-MONOMER

    Source assertion: GLYOXI-MONOMER has an explicit UniProt unification cross-reference P0AC81.

    Source location/ptools-xml/Protein[@frameid="GLYOXI-MONOMER"]/dblink[dblink-db="UNIPROT"]
  • PMID:9628737
    gel filtration analysis indicated GlxI to be a homodimer of 30 kDa.
glyoxalase I
MetaCyc:GLYOXI-CPLX		catalyzes

GloA isomerizes the hemithioacetal formed spontaneously from methylglyoxal and glutathione. The Rhea net equation folds the preceding spontaneous equilibrium into the conversion; it is not evidence that GloA catalyzes initial condensation.

methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071
  • MetaCyc:GLYOXI-CPLX

    Source assertion: The complex catalyzes GLYOXI-ENZRXN, whose reaction is GLYOXI-RXN.

    Source location/ptools-xml/Protein[@frameid="GLYOXI-CPLX"]/catalyzes/Enzymatic-Reaction[@frameid="GLYOXI-ENZRXN"]
  • UniProtKB:P0AC81

    Source assertion: FUNCTION specifies spontaneous hemithioacetal formation followed by GloA isomerization; catalytic annotation names RHEA:19069 with ECO:0000269/PMID10913283.

    Source location/comments/0; /comments/1/reaction
  • RHEA:19069

    Source assertion: RHEA:19071 is the right-to-left directional member of master RHEA:19069, producing (R)-S-lactoylglutathione.

    Source locationhttp://rdf.rhea-db.org/19069 rh:directionalReaction; http://rdf.rhea-db.org/19071 rh:substrates/rh:products
  • PathBank:SMP0002125

    Source assertion: Native ReactionCatalysis/6107 assigns glyoxalase I complex ProteinComplex/4108 to Reactions/6149; the complex contains two Protein/6205 chains, whose reference identifies P0AC81.

    Source locationPW002113.owl#ReactionCatalysis/6107; #ProteinComplex/4108; #Protein/6205/Stoichiometry/2.0; #ProteinReference/6205
Hydroxyacylglutathione hydrolase GloB
UniProtKB:P0AC84		catalyzes

Monomeric GloB hydrolyzes the R-specific thioester. This is the source map’s GloB branch; GloC provides an experimentally supported accessory isoenzyme but is not required to invent an additional chemical step.

(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246
  • UniProtKB:P0AC84

    Source assertion: The specific (R)-S-lactoylglutathione hydrolysis is RHEA:25245 (ECO:0000269/PMID17196158,25670698); SUBUNIT says monomer (ECO:0000269/PMID17196158).

    Source location/comments/2/reaction; /comments/7
  • RHEA:25245

    Source assertion: RHEA:25246 is the left-to-right directional member of RHEA:25245.

    Source locationhttp://rdf.rhea-db.org/25245 rh:directionalReaction; http://rdf.rhea-db.org/25246 rh:substrates/rh:products
  • PMID:17196158
    Glyoxalase II (Glx II) hydrolyzes the thioester into d-lactate and free glutathione.
  • PathBank:SMP0002125

    Source assertion: Native ReactionCatalysis/6108 assigns Protein/6206 (UniProt P0AC84) to Reactions/6150. Its L-lactate label/xref is contradicted by the independently inspected R-specific enzyme chemistry.

    Source locationPW002113.owl#ReactionCatalysis/6108; #ProteinReference/6206; #Reactions/6150; #CompoundReference/PW_C000122
  • PMID:25670698
    The two isoenzymes have additive effects and ensure maximal MG degradation.
Quinone-dependent D-lactate dehydrogenase
UniProtKB:P06149		catalyzes

Respiratory Dld oxidizes D-(R)-lactate using enzyme-bound FAD and a quinone acceptor. The generic Rhea class is faithful to current annotation; no UQ6 specificity, NAD dependence or direct proton pumping by Dld is inferred. The inspected 1986 reconstitution used ubiquinone-8; its electron-transfer step was not electrogenic.

(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469
  • UniProtKB:P06149

    Source assertion: Dld catalytic annotation names RHEA:51468: (R)-lactate + a quinone = a quinol + pyruvate; ECO:0000269/PMID3013300,7578233 and ECO:0000255/HAMAP MF_02092.

    Source location/comments/1/reaction
  • RHEA:51468

    Source assertion: RHEA:51469 is the left-to-right directional member of RHEA:51468, using the exact ChEBI quinone and quinol classes.

    Source locationhttp://rdf.rhea-db.org/51468 rh:directionalReaction; http://rdf.rhea-db.org/51469 rh:substrates/rh:products
  • PathBank:SMP0002125

    Source assertion: Native ReactionCatalysis/6109 assigns Protein/5893 (UniProt P06149) to Reactions/6151. The L-lactate and UQ6 assignments are not imported as exact Rhea equivalences.

    Source locationPW002113.owl#ReactionCatalysis/6109; #ProteinReference/5893; #Reactions/6151
  • PMID:3013300
    proteoliposomes reconstituted with purified D-lactate dehydrogenase, ubiquinone 8, and purified cytochrome o
glyoxalase I
MetaCyc:GLYOXI-CPLX		has_cofactor

Ni2+ activates E. coli GloA, whereas Zn2+ does not. Current annotation of the 2000 structures reports one Ni per subunit/two per dimer; the 1998 solution study reported one Ni per dimer. These are differing measurements, not a universal physiological occupancy. Co2+ and Cd2+ also activated protein-metal complexes in the structural study.

nickel(2+)
CHEBI:49786
  • UniProtKB:P0AC81

    Source assertion: COFACTOR: Ni2+ (ECO:0000269/PMID10913283); note reports one nickel per subunit/two between dimer subunits and inactivity with Zn2+.

    Source location/comments/2/cofactors; /comments/2/note
  • PMID:10913283
    the Escherichia coli enzyme is inactive in the presence of Zn(2+) and is maximally active with Ni(2+).
  • PMID:9628737

    Source assertion: The indexed abstract reports one nickel ion per dimeric enzyme by inductively coupled plasma and atomic absorption analyses; this differs from the later structured annotation.

    Source location/resultList/result[0]/abstractText, metal-analysis sentences
Hydroxyacylglutathione hydrolase GloB
UniProtKB:P0AC84		has_cofactor

Current annotation reports two Zn2+ ions per GloB monomer. Mn2+ and Co2+ substitute in reconstitution experiments; this is not a claim of in vivo metal substitution. Neither GloA nickel dependence nor other organisms’ mixed metals are transferred to GloB.

zinc(2+)
CHEBI:29105
  • UniProtKB:P0AC84

    Source assertion: GloB binds two Zn2+ ions per subunit (ECO:0000269/PMID17196158); Mn2+ and Co2+ can replace zinc in reconstitution experiments.

    Source location/comments/3/cofactors; /comments/3/note
Quinone-dependent D-lactate dehydrogenase
UniProtKB:P06149		has_cofactor

FAD is bound to Dld and cycles redox state during turnover; it is not a freely consumed substrate in the net quinone reaction. The ChEBI charge state follows current UniProt grounding.

FAD(3-)
CHEBI:57692
  • UniProtKB:P06149

    Source assertion: COFACTOR identifies FAD/CHEBI:57692 with experimental support from PMID10944213,4575624,4582730,7578233, alongside HAMAP inference.

    Source location/comments/2/cofactors
  • PMID:10944213
    a noncovalently bound FAD cofactor
Quinone-dependent D-lactate dehydrogenase
UniProtKB:P06149		located_in

Dld is a peripheral enzyme on the cytoplasmic side of the E. coli inner (plasma) membrane. The edge does not encode integral topology or a universal location for the whole pathway.

plasma membrane
GO:0005886
  • UniProtKB:P06149

    Source assertion: SUBCELLULAR LOCATION: cell inner membrane, peripheral membrane protein, cytoplasmic side; experimental citations include PMID1092688,4575624,4582730 alongside HAMAP.

    Source location/comments/5/subcellularLocations/0
  • PMID:10944213
    located on the cytoplasmic side of the inner membrane
methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071		part_of

Native reaction membership plus an independently grounded selected Rhea direction. The Dld bridge uses matching catalyst and chemistry, not a fabricated exact-match cross-reference.

MetaCyc:PWY-5386
  • MetaCyc:PWY-5386

    Source assertion: PWY-5386 explicitly lists GLYOXI-RXN; its reaction-layout selects R2L.

    Source location/ptools-xml/Pathway[@frameid="PWY-5386"]/reaction-list; reaction-layout[Reaction/@frameid="GLYOXI-RXN"]
  • MetaCyc:GLYOXI-RXN

    Source assertion: GLYOXI-RXN has native Rhea unification cross-reference 19072; this is the bidirectional family member, not the selected directed accession.

    Source location/ptools-xml/Reaction[@frameid="GLYOXI-RXN"]/dblink[dblink-db="RHEA"]
  • RHEA:19069

    Source assertion: Master RHEA:19069 explicitly has bidirectionalReaction RHEA:19072 and directionalReaction RHEA:19071.

    Source locationhttp://rdf.rhea-db.org/19069 rh:bidirectionalReaction http://rdf.rhea-db.org/19072; rh:directionalReaction http://rdf.rhea-db.org/19071
(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246		part_of

Native reaction membership plus an independently grounded selected Rhea direction. The Dld bridge uses matching catalyst and chemistry, not a fabricated exact-match cross-reference.

MetaCyc:PWY-5386
  • MetaCyc:PWY-5386

    Source assertion: PWY-5386 explicitly lists GLYOXII-RXN; its reaction-layout selects L2R.

    Source location/ptools-xml/Pathway[@frameid="PWY-5386"]/reaction-list; reaction-layout[Reaction/@frameid="GLYOXII-RXN"]
  • MetaCyc:GLYOXII-RXN

    Source assertion: GLYOXII-RXN has native Rhea unification cross-reference 25245; this is the master, not the selected directed accession.

    Source location/ptools-xml/Reaction[@frameid="GLYOXII-RXN"]/dblink[dblink-db="RHEA"]
  • RHEA:25245

    Source assertion: Master RHEA:25245 explicitly has directionalReaction RHEA:25246.

    Source locationhttp://rdf.rhea-db.org/25245 rh:directionalReaction http://rdf.rhea-db.org/25246
(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469		part_of

Native reaction membership plus an independently grounded selected Rhea direction. The Dld bridge uses matching catalyst and chemistry, not a fabricated exact-match cross-reference.

MetaCyc:PWY-5386
  • MetaCyc:PWY-5386

    Source assertion: PWY-5386 explicitly lists DLACTDEHYDROGFAD-RXN; its reaction-layout selects L2R.

    Source location/ptools-xml/Pathway[@frameid="PWY-5386"]/reaction-list; reaction-layout[Reaction/@frameid="DLACTDEHYDROGFAD-RXN"]
  • MetaCyc:DLACTDEHYDROGFAD-RXN

    Source assertion: Native reaction consumes D-LACTATE and Ubiquinones, producing PYRUVATE and Ubiquinols; it has no explicit Rhea dblink.

    Source location/ptools-xml/Reaction[@frameid="DLACTDEHYDROGFAD-RXN"]/left; /right
  • UniProtKB:P06149

    Source assertion: The native Dld controller P06149 is independently assigned RHEA:51468; the current Rhea reaction uses broader quinone/quinol classes.

    Source location/comments/1/reaction; /uniProtKBCrossReferences[database="BioCyc"]
  • RHEA:51468

    Source assertion: Master RHEA:51468 explicitly has directionalReaction RHEA:51469.

    Source locationhttp://rdf.rhea-db.org/51468 rh:directionalReaction http://rdf.rhea-db.org/51469
methylglyoxal + glutathione => (R)-S-lactoylglutathione
RHEA:19071		provides_input_for

The R-specific lactoylglutathione product is the GloB substrate; glutathione is regenerated by hydrolysis.

(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246
  • RHEA:19069

    Source assertion: RHEA:19071 produces CHEBI:57474.

    Source locationhttp://rdf.rhea-db.org/19071 rh:products; http://rdf.rhea-db.org/19069_L rh:contains1
  • RHEA:25245

    Source assertion: RHEA:25246 consumes CHEBI:57474 and produces CHEBI:57925.

    Source locationhttp://rdf.rhea-db.org/25246 rh:substrates/rh:products
  • UniProtKB:P0AC84

    Source assertion: FUNCTION identifies the hydrolysis of (R)-S-lactoylglutathione to (R)-lactate and glutathione, with ECO:0000269 primary citations.

    Source location/comments/0
(R)-S-lactoylglutathione + H2O => (R)-lactate + glutathione + H(+)
RHEA:25246		provides_input_for

GloB-derived D-lactate feeds Dld oxidation to pyruvate. The 2022 physiological test used MG1655-derived SIJ488 glycolysis mutants on glycerol; it does not prove identical basal flux in every K-12 condition or GloB exclusivity over GloC.

(R)-lactate + a quinone => a quinol + pyruvate
RHEA:51469
  • RHEA:25245

    Source assertion: RHEA:25246 produces CHEBI:16004, the R-specific lactate.

    Source locationhttp://rdf.rhea-db.org/25246 rh:products; http://rdf.rhea-db.org/25245_R rh:contains1
  • RHEA:51468

    Source assertion: RHEA:51469 consumes CHEBI:16004 and produces pyruvate.

    Source locationhttp://rdf.rhea-db.org/51469 rh:substrates/rh:products
  • PMID:37850128
    the absence of GloA or Dld completely abolished growth on glycerol

References

Curation history