methylglyoxal degradation III

MetaCyc:PWY-5453

The glutathione-independent acetol branch of methylglyoxal degradation III in Escherichia coli uses Gpr/YghZ to reduce methylglyoxal with NADPH and GldA to reduce acetol with NADH. The record represents the native MG1655 pathway annotation with K-12 enzyme and mutant evidence. Purified YghZ produces acetol; NADH activity and the reverse reaction were negligible or undetected under the reported conditions. The (S)-propanediol product is retained as a current Rhea/UniProt annotation, not an enantiomer-resolved result of the inspected 2005 NMR experiments. A separate engineered AG1 study produced R-propanediol through a proposed lactaldehyde route and does not establish the stereochemistry of this acetol branch. Native physiological flux, exclusive enzyme roles and a fixed GldA oligomeric state are not implied. YghZ also acts on L-glyceraldehyde 3-phosphate; other methylglyoxal reductases provide parallel activities. Transport and neighboring lactaldehyde, glyoxalase and glycerol-utilization reactions are outside this two-reaction record.

Pathway type

methylglyoxal detoxification

Organism scope

Escherichia coli str. K-12 substr. MG1655 NCBITaxon:511145

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Pathway network

15 nodes · 17 asserted directed edges

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Reaction / activity
Chemical / cofactor
Protein / complex
Pathway
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli str. K-12 substr. MG1655 `NCBITaxon:511145`	taxon
hydron `CHEBI:15378`	small molecule
methylglyoxal `CHEBI:17158`	small molecule
hydroxyacetone `CHEBI:27957`	small molecule
(S)-propane-1,2-diol `CHEBI:29002`	small molecule
NADPH(4-) `CHEBI:57783`	small molecule
NADP(3-) `CHEBI:58349`	small molecule
NAD(1-) `CHEBI:57540`	small molecule
NADH(2-) `CHEBI:57945`	small molecule
zinc(2+) `CHEBI:29105`	cofactor
L-glyceraldehyde 3-phosphate reductase `UniProtKB:Q46851`	protein
Glycerol dehydrogenase `UniProtKB:P0A9S5`	protein
L-1,2-propanediol dehydrogenase / glycerol dehydrogenase `MetaCyc:GLYCDEH-CPLX`	complex
methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	molecular activity	right to left
hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
methylglyoxal `CHEBI:17158`	consumes	methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	RHEA:27988 Source assertion: Rhea RHEA:27988 assigns CHEBI:17158 to its substrates, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27988']/rh:substrates; rdf:Description[@rdf:about='http://rdf.rhea-db.org/27986_R']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_27986_compound_4547']; rh:compound/rh:chebi`
NADPH(4-) `CHEBI:57783`	consumes	methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	RHEA:27988 Source assertion: Rhea RHEA:27988 assigns CHEBI:57783 to its substrates, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27988']/rh:substrates; rdf:Description[@rdf:about='http://rdf.rhea-db.org/27986_R']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_27986_compound_3438']; rh:compound/rh:chebi`
hydron `CHEBI:15378`	consumes	methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	RHEA:27988 Source assertion: Rhea RHEA:27988 assigns CHEBI:15378 to its substrates, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27988']/rh:substrates; rdf:Description[@rdf:about='http://rdf.rhea-db.org/27986_R']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_27986_compound_3249']; rh:compound/rh:chebi`
methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	produces	hydroxyacetone `CHEBI:27957`	RHEA:27988 Source assertion: Rhea RHEA:27988 assigns CHEBI:27957 to its products, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27988']/rh:products; rdf:Description[@rdf:about='http://rdf.rhea-db.org/27986_L']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_27986_compound_6312']; rh:compound/rh:chebi`
methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	produces	NADP(3-) `CHEBI:58349`	RHEA:27988 Source assertion: Rhea RHEA:27988 assigns CHEBI:58349 to its products, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27988']/rh:products; rdf:Description[@rdf:about='http://rdf.rhea-db.org/27986_L']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_27986_compound_5188']; rh:compound/rh:chebi`
hydroxyacetone `CHEBI:27957`	consumes	hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	RHEA:28668 Source assertion: Rhea RHEA:28668 assigns CHEBI:27957 to its substrates, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28668']/rh:substrates; rdf:Description[@rdf:about='http://rdf.rhea-db.org/28667_L']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_28667_compound_6312']; rh:compound/rh:chebi`
NADH(2-) `CHEBI:57945`	consumes	hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	RHEA:28668 Source assertion: Rhea RHEA:28668 assigns CHEBI:57945 to its substrates, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28668']/rh:substrates; rdf:Description[@rdf:about='http://rdf.rhea-db.org/28667_L']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_28667_compound_1650']; rh:compound/rh:chebi`
hydron `CHEBI:15378`	consumes	hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	RHEA:28668 Source assertion: Rhea RHEA:28668 assigns CHEBI:15378 to its substrates, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28668']/rh:substrates; rdf:Description[@rdf:about='http://rdf.rhea-db.org/28667_L']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_28667_compound_3249']; rh:compound/rh:chebi`
hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	produces The (S) product is the current Rhea/UniProt and native pathway annotation. The inspected 2005 NMR study did not resolve diol enantiomers. Engineered AG1 R-diol production in PMID:10049880 was assigned to a lactaldehyde route and does not directly test this exact GldA acetol step.	(S)-propane-1,2-diol `CHEBI:29002`	RHEA:28668 Source assertion: Rhea RHEA:28668 assigns CHEBI:29002 to its products, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28668']/rh:products; rdf:Description[@rdf:about='http://rdf.rhea-db.org/28667_R']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_28667_compound_5131']; rh:compound/rh:chebi`
hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	produces	NAD(1-) `CHEBI:57540`	RHEA:28668 Source assertion: Rhea RHEA:28668 assigns CHEBI:57540 to its products, with coefficient 1 in rh:contains1. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28668']/rh:products; rdf:Description[@rdf:about='http://rdf.rhea-db.org/28667_R']/rh:contains1[@rdf:resource='http://rdf.rhea-db.org/Participant_28667_compound_3484']; rh:compound/rh:chebi`
L-glyceraldehyde 3-phosphate reductase `UniProtKB:Q46851`	enables Functional Gpr/YghZ activity is represented without asserting a monomeric physical catalyst. Current UniProt reports tetrameric and octameric assemblies in different studies. Its methylglyoxal activity is much less efficient than its L-glyceraldehyde 3-phosphate reductase activity; this is not an exclusive substrate or physiological-role claim.	methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	PMID:16077126 Source assertion: Purified YghZ converts methylglyoxal to acetol with NADPH by NMR. NADH activity was below 3% of NADPH activity; the reverse acetol-to-methylglyoxal reaction was not detected under the assay conditions. Source location `PMC1196063: Results, Reduction of methylglyoxal to acetol by purified E. coli AKRs; Figure 3B; Table 2` UniProtKB:Q46851 Source assertion: Reviewed Q46851 assigns hydroxyacetone/NADP versus methylglyoxal/NADPH chemistry to RHEA:27986, citing ECO:0000269 PMID:16077126 and ECO:0000305 PMID:12583903. Source location `/comments/2/reaction; /genes/0; /primaryAccession`
L-1,2-propanediol dehydrogenase / glycerol dehydrogenase `MetaCyc:GLYCDEH-CPLX`	catalyzes The (S) product is the current Rhea/UniProt and native pathway annotation. The inspected 2005 NMR study did not resolve diol enantiomers. Engineered AG1 R-diol production in PMID:10049880 was assigned to a lactaldehyde route and does not directly test this exact GldA acetol step. This retains a reviewed enzyme-function assertion; the cited older experiments were not all inspected as full texts. NADH is the selected branch, not a claim that no NADPH-supported activity exists.	hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	MetaCyc:RXN-8632 Source assertion: RXN-8632 has ENZRXN0-6324 with GLYCDEH-CPLX as enzyme, a RHEA:28667 cross-reference and acetol/NADH/proton opposite (S)-propane-1,2-diol/NAD. PWY-5453 selects the reduction direction. Source location `Reaction[@frameid="RXN-8632"]/enzymatic-reaction/Enzymatic-Reaction[@frameid="ENZRXN0-6324"]/enzyme; left; right; dblink` UniProtKB:P0A9S5 Source assertion: Reviewed GldA explicitly assigns hydroxyacetone + NADH + H(+) = (S)-propane-1,2-diol + NAD(+) to RHEA:28667, with ECO:0000269 citations 18179582,3920199,40950,6365902. Source location `/comments/2/reaction; /primaryAccession`
Glycerol dehydrogenase `UniProtKB:P0A9S5`	part_of The native octamer coefficient is condition-dependent. This edge records component membership only; it does not assert that all catalysis requires an octamer or excludes tetramers/dimers.	L-1,2-propanediol dehydrogenase / glycerol dehydrogenase `MetaCyc:GLYCDEH-CPLX`	MetaCyc:GLYCDEH-CPLX Source assertion: GLYCDEH-CPLX contains GLYCDEH-MONOMER with coefficient 8 and explicitly notes an active dimer. This supports membership without an invariant assembly stoichiometry. Source location `Protein[@frameid="GLYCDEH-CPLX"]/component; comment` MetaCyc:GLYCDEH-MONOMER Source assertion: The native GLYCDEH-MONOMER has the exact UniProt cross-reference P0A9S5. Source location `Protein[@frameid="GLYCDEH-MONOMER"]/dblink[dblink-db="UNIPROT"]/dblink-oid` PMID:30839292 Source assertion: Purified E. coli GldA eluted as a homogeneous tetramer in 5% glycerol; the authors contrast reported dimer/octamer mixtures without glycerol. Source location `PMC6404857: Results and discussion 3.1, Protein purification; Figure 1b`
Glycerol dehydrogenase `UniProtKB:P0A9S5`	has_cofactor The crystal demonstrates bound zinc; it is not an apo-enzyme metal-reconstitution assay for acetol reduction. NAD+ in the 2019 structural illustration was modeled from another structure, not observed in that crystal.	zinc(2+) `CHEBI:29105`	UniProtKB:P0A9S5 Source assertion: Reviewed GldA names Zn(2+) as cofactor with ECO:0000305 PMID:30839292; its note says one zinc ion per subunit with ECO:0000269 for the same paper. Source location `/comments/4/cofactors/0; /comments/4/note` PMID:30839292 Source assertion: The E. coli GldA structure contains active-site Zn2+ coordinated by His254, His271 and Asp171 and interacting with glycerol. Source location `PMC6404857: Results and discussion 3.3, Overall structural details; Figure 3`
methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	part_of	`MetaCyc:PWY-5453`	MetaCyc:PWY-5453 Source assertion: PWY-5453 lists RXN0-4281 in methylglyoxal degradation III and chooses its reductive direction in reaction-layout. The graph restricts the multispecies definition to the supported E. coli branch. Source location `Pathway[@frameid="PWY-5453"]/reaction-list/Reaction[@frameid="RXN0-4281"]; reaction-layout; species` MetaCyc:RXN0-4281 Source assertion: Native RXN0-4281 provides the exact chemical sides and Rhea master cross-reference for the selected directional reaction. Source location `Reaction/left; right; reaction-direction; dblink[dblink-db="RHEA"]`
hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	part_of	`MetaCyc:PWY-5453`	MetaCyc:PWY-5453 Source assertion: PWY-5453 lists RXN-8632 in methylglyoxal degradation III and chooses its reductive direction in reaction-layout. The graph restricts the multispecies definition to the supported E. coli branch. Source location `Pathway[@frameid="PWY-5453"]/reaction-list/Reaction[@frameid="RXN-8632"]; reaction-layout; species` MetaCyc:RXN-8632 Source assertion: Native RXN-8632 provides the exact chemical sides and Rhea master cross-reference for the selected directional reaction. Source location `Reaction/left; right; reaction-direction; dblink[dblink-db="RHEA"]`
methylglyoxal + NADPH + H(+) => hydroxyacetone + NADP(+) `RHEA:27988`	provides_input_for This is the annotated acetol-connected two-enzyme route. The 2005 diol observation is from engineered MG-accumulating CK281 derivatives or crude extracts, not a purified two-enzyme reconstitution or proof of unrestricted MG1655 flux.	hydroxyacetone + NADH + H(+) => (S)-propane-1,2-diol + NAD(+) `RHEA:28668`	MetaCyc:PWY-5453 Source assertion: PWY-5453 orders RXN0-4281 before RXN-8632, with acetol as the shared intermediate and both reactions selected in the reductive direction. Source location `Pathway[@frameid="PWY-5453"]/reaction-ordering[Reaction[@frameid="RXN-8632"]]/predecessor-reactions; reaction-layout` PMID:16077126 Source assertion: The MG-accumulating strain and crude extracts produced acetol followed by small amounts of 1,2-propanediol; purified AKRs produced acetol but no detectable diol. Source location `PMC1196063: Results, Detection of acetol from methylglyoxal-producing E. coli cells; Figure 2; MG-reducing activity in crude extracts; Figure 3B`

References

MetaCyc:PWY-5453 MetaCyc PWY-5453 (source version: 22.5; official mirror retrieved 2026-10-10)
MetaCyc:RXN0-4281 MetaCyc RXN0-4281 (source version: 22.5; official mirror retrieved 2026-10-10)
MetaCyc:RXN-8632 MetaCyc RXN-8632 (source version: 22.5; official mirror retrieved 2026-10-10)
MetaCyc:GLYCDEH-CPLX MetaCyc GLYCDEH-CPLX (source version: 22.5; official mirror retrieved 2026-10-10)
MetaCyc:GLYCDEH-MONOMER MetaCyc GLYCDEH-MONOMER (source version: 22.5; official mirror retrieved 2026-10-10)
UniProtKB:Q46851 Reviewed UniProtKB Q46851 (source version: 2026_03; response release header and entry retrieved 2026-10-10)
UniProtKB:P0A9S5 Reviewed UniProtKB P0A9S5 (source version: 2026_03; response release header and entry retrieved 2026-10-10)
RHEA:27988 Rhea 27988 directional reaction (source version: 142 (2026-09-02))
RHEA:28668 Rhea 28668 directional reaction (source version: 142 (2026-09-02))
PMID:16077126 Conversion of methylglyoxal to acetol by Escherichia coli aldo-keto reductases. (source version: Primary full text; retrieved 2026-10-10)
PMID:30839292 Structure of glycerol dehydrogenase (GldA) from Escherichia coli. (source version: Primary full text; retrieved 2026-10-10)
PMID:10049880 Metabolic engineering of a 1,2-propanediol pathway in Escherichia coli. (source version: Primary full text; retrieved 2026-10-10)

Curation history

2026-10-10T23:32:06Z codex
- CREATE — Add the two-reaction E. coli methylglyoxal acetol branch
  Added MetaCyc:PWY-5453 with exact directed Rhea27988/28668 chemistry, functional Gpr, the native GldA complex, component membership and zinc annotation. Preserved stereochemical annotation versus inspected assay limits, assembly variability and physiological scope; excluded unverified transport and neighboring branches. Author source replay passed; independent reviews and full publication gates are recorded separately.
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