2-methylcitrate cycle I
MetaCyc:PWY0-42
Complete five-reaction MetaCyc route from propanoate activation through methylcitrate synthesis, dehydration, aconitase hydration and methylisocitrate cleavage to pyruvate and succinate, represented for Escherichia coli K-12 with primary experiments separately scoped to their strains and preparations. The central methylcitrate stereochemistry remains experimentally disputed. Approved stereounspecified Rhea reactions 57493 and 57497 and CHEBI:15598 preserve the established transformations without selecting an absolute stereoisomer or claiming all stereoisomers are substrates. These are broader reactions than the stereospecific native annotations, not exact replacements. PrpC and PrpB assemblies are explicit; AcnB monomer/dimer behavior is conditional. Acs and PrpE are alternative activation roles with different evidence strength. Oxaloacetate regeneration by the TCA cycle is outside the five-member native definition.
- Pathway type
- propionate catabolic pathway
- Organism scope
Pathway network
30 nodes · 41 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.
- Reaction / activity
- Chemical / cofactor
- Protein / complex
- Pathway
- Solid arrow: mechanistic relation
- Dashed arrow: membership, location or cofactor relation
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Escherichia coli str. K-12 substr. MG1655NCBITaxon:511145 | taxon | |
pyruvateCHEBI:15361 | small molecule | |
waterCHEBI:15377 | small molecule | |
hydronCHEBI:15378 | small molecule | |
2-methylcitrate(3-)CHEBI:15598 | small molecule | |
oxaloacetate(2-)CHEBI:16452 | small molecule | |
propionateCHEBI:17272 | small molecule | |
magnesium(2+)CHEBI:18420 | cofactor | |
succinate(2-)CHEBI:30031 | small molecule | |
ATP(4-)CHEBI:30616 | small molecule | |
diphosphate(3-)CHEBI:33019 | small molecule | |
adenosine 5'-monophosphate(2-)CHEBI:456215 | small molecule | |
tetra-mu3-sulfido-tetraironCHEBI:49883 | cofactor | |
coenzyme A(4-)CHEBI:57287 | small molecule | |
propionyl-CoA(4-)CHEBI:57392 | small molecule | |
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateCHEBI:57429 | small molecule | |
(Z)-but-2-ene-1,2,3-tricarboxylateCHEBI:57872 | small molecule | |
Propionate--CoA ligaseUniProtKB:P77495 | protein | |
Acetyl-coenzyme A synthetaseUniProtKB:P27550 | protein | |
2-methylcitrate synthaseUniProtKB:P31660 | protein | |
2-methylcitrate dehydrataseUniProtKB:P77243 | protein | |
Aconitate hydratase BUniProtKB:P36683 | protein | |
2-methylisocitrate lyaseUniProtKB:P77541 | protein | |
2-methylcitrate synthaseMetaCyc:CPLX0-251 | complex | |
2-methylisocitrate lyaseMetaCyc:CPLX0-1021 | complex | |
propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 | molecular activity | left to right |
propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 | molecular activity | left to right |
2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 | molecular activity | left to right |
2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 | molecular activity | right to left |
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 | molecular activity | left to right |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
propionateCHEBI:17272 | consumes | propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 |
|
ATP(4-)CHEBI:30616 | consumes | propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 |
|
coenzyme A(4-)CHEBI:57287 | consumes | propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 |
|
propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 | produces | propionyl-CoA(4-)CHEBI:57392 |
|
propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 | produces | adenosine 5'-monophosphate(2-)CHEBI:456215 |
|
propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 | produces | diphosphate(3-)CHEBI:33019 |
|
propionyl-CoA(4-)CHEBI:57392 | consumes | propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 |
|
oxaloacetate(2-)CHEBI:16452 | consumes | propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 |
|
waterCHEBI:15377 | consumes | propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 |
|
propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 | produces Stereounspecified source identity: this edge leaves methylcitrate absolute configuration unresolved and does not assert utilization or production of every stereoisomer. | 2-methylcitrate(3-)CHEBI:15598 |
|
propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 | produces | coenzyme A(4-)CHEBI:57287 |
|
propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 | produces | hydronCHEBI:15378 |
|
2-methylcitrate(3-)CHEBI:15598 | consumes Stereounspecified source identity: this edge leaves methylcitrate absolute configuration unresolved and does not assert utilization or production of every stereoisomer. | 2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 |
|
2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 | produces | (Z)-but-2-ene-1,2,3-tricarboxylateCHEBI:57872 |
|
2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 | produces | waterCHEBI:15377 |
|
(Z)-but-2-ene-1,2,3-tricarboxylateCHEBI:57872 | consumes | 2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 |
|
waterCHEBI:15377 | consumes | 2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 |
|
2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 | produces | (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateCHEBI:57429 |
|
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateCHEBI:57429 | consumes | (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 |
|
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 | produces | pyruvateCHEBI:15361 |
|
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 | produces | succinate(2-)CHEBI:30031 |
|
propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 | part_of | MetaCyc:PWY0-42 |
|
propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 | part_of The native reaction is stereospecific. This membership uses the separately issued generic parent reaction to represent the same supported pathway transformation while leaving the disputed methylcitrate configuration unspecified; no exactMatch is asserted. | MetaCyc:PWY0-42 |
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2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 | part_of The native reaction is stereospecific. This membership uses the separately issued generic parent reaction to represent the same supported pathway transformation while leaving the disputed methylcitrate configuration unspecified; no exactMatch is asserted. | MetaCyc:PWY0-42 |
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2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 | part_of | MetaCyc:PWY0-42 |
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(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 | part_of | MetaCyc:PWY0-42 |
|
propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 | provides_input_for Material transfer through CHEBI:57392. Ordering is not a thermodynamic irreversibility claim. | propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 |
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propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 | provides_input_for Material transfer through CHEBI:15598; the methylcitrate transfer retains an unspecified absolute configuration. | 2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 |
|
2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 | provides_input_for Material transfer through CHEBI:57872. Ordering is not a thermodynamic irreversibility claim. | 2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 |
|
2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 | provides_input_for Material transfer through CHEBI:57429. Ordering is not a thermodynamic irreversibility claim. | (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 |
|
2-methylcitrate synthaseUniProtKB:P31660 | part_of Native assembly stoichiometry is 2 identical subunits; membership does not assert individual-subunit sufficiency. | 2-methylcitrate synthaseMetaCyc:CPLX0-251 |
|
2-methylisocitrate lyaseUniProtKB:P77541 | part_of Native assembly stoichiometry is 4 identical subunits; membership does not assert individual-subunit sufficiency. | 2-methylisocitrate lyaseMetaCyc:CPLX0-1021 |
|
Propionate--CoA ligaseUniProtKB:P77495 | enables Alternative annotated activation role. The E. coli reviewed FUNCTION is similarity-derived; the 2002 propionate-growth study favored Acs under its conditions. No essentiality or measured PrpE flux is asserted. | propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 |
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Acetyl-coenzyme A synthetaseUniProtKB:P27550 | enables Native curated propionate activation role plus condition-specific primary physiological inference. Current UniProt CATALYTIC ACTIVITY describes acetate activation, not this propionate equation; it is not used as direct support for substrate promiscuity or exclusive Acs dependence. | propanoate + ATP + CoA => propanoyl-CoA + AMP + diphosphateRHEA:20374 |
|
2-methylcitrate synthaseMetaCyc:CPLX0-251 | catalyzes The catalytic transformation is established; its exact methylcitrate stereochemical product is not selected. The source-issued generic reaction is used, not a modified RHEA:23781 equation. | propanoyl-CoA + oxaloacetate + H2O => 2-methylcitrate + CoA + H(+)RHEA:57493 |
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2-methylcitrate dehydrataseUniProtKB:P77243 | catalyzes This records the physiological cis-product branch, not universal stereoisomer acceptance. Native curation preserves disagreement over whether PrpD contains an iron-sulfur cluster; one primary study reports an unstable [2Fe-2S] cluster in its preparation. No obligatory cofactor or cofactor-independence edge is asserted. | 2-methylcitrate => 2-methyl-cis-aconitate + H2ORHEA:57497 |
|
Aconitate hydratase BUniProtKB:P36683 | enables Functional gene-product role, without fixing a condition-independent oligomeric state. Native CPLX0-7761 has one component without a coefficient; current evidence supports conditional monomer/dimer behavior. The catabolic hydration is Rhea right-to-left relative to the master equation. | 2-methyl-cis-aconitate + H2O => (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylateRHEA:17943 |
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2-methylisocitrate lyaseMetaCyc:CPLX0-1021 | catalyzes | (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate => pyruvate + succinateRHEA:16810 |
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Acetyl-coenzyme A synthetaseUniProtKB:P27550 | has_cofactor Protein-level curated cofactor annotation; alternative-metal ranking is source-specific, not a newly measured propionate-specific metal series. | magnesium(2+)CHEBI:18420 |
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Aconitate hydratase BUniProtKB:P36683 | has_cofactor Catalytically active aconitase context; apo-AcnB RNA regulation and oxidative-stress effects are outside the chemical route. | tetra-mu3-sulfido-tetraironCHEBI:49883 |
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2-methylisocitrate lyaseMetaCyc:CPLX0-1021 | has_cofactor | magnesium(2+)CHEBI:18420 |
|
References
MetaCyc:2-METHYLCITRATE-DEHYDRATASE-RXNMetaCyc 2-METHYLCITRATE-DEHYDRATASE-RXN native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:2-METHYLCITRATE-SYNTHASE-RXNMetaCyc 2-METHYLCITRATE-SYNTHASE-RXN native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:4.2.1.99-RXNMetaCyc 4.2.1.99-RXN native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:ACS-MONOMERMetaCyc ACS-MONOMER native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:CPLX0-1021MetaCyc CPLX0-1021 native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:CPLX0-251MetaCyc CPLX0-251 native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:G6196-MONOMERMetaCyc G6196-MONOMER native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:G6198-MONOMERMetaCyc G6198-MONOMER native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:G6199-MONOMERMetaCyc G6199-MONOMER native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:G6200-MONOMERMetaCyc G6200-MONOMER native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:METHYLISOCITRATE-LYASE-RXNMetaCyc METHYLISOCITRATE-LYASE-RXN native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:PROPIONATE--COA-LIGASE-RXNMetaCyc PROPIONATE--COA-LIGASE-RXN native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)MetaCyc:PWY0-42MetaCyc PWY0-42 native XML (source version: MetaCyc public native XML; mirror 22.5; complete response body)PMID:114223892-Methylisocitrate lyases from the bacterium Escherichia coli and the filamentous fungus Aspergillus nidulans: characterization and comparison of both enzymes. (source version: 2001 primary abstract via Europe PMC exact-PMID JSON; digest covers full API response)PMID:11782506AcnC of Escherichia coli is a 2-methylcitrate dehydratase (PrpD) that can use citrate and isocitrate as substrates. (source version: 2002 primary abstract via Europe PMC exact-PMID JSON; digest covers full API response)PMID:12473114Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase. (source version: 2002 primary abstract via Europe PMC exact-PMID JSON; digest covers full API response)PMID:12706720Crystal structure of 2-methylisocitrate lyase (PrpB) from Escherichia coli and modelling of its ligand bound active centre. (source version: 2003 primary abstract via Europe PMC exact-PMID JSON; digest covers full API response)PMID:28956599First Biochemical Characterization of a Methylcitric Acid Cycle from Bacillus subtilis Strain 168. (source version: 2017 primary abstract via Europe PMC exact-PMID JSON; digest covers full API response)RHEA:16810Rhea 142 directed reaction 16810 and family (source version: Rhea 142, 2026-09-02; SHA256 is the full compressed official RDF gzip)RHEA:17943Rhea 142 directed reaction 17943 and family (source version: Rhea 142, 2026-09-02; SHA256 is the full compressed official RDF gzip)RHEA:20374Rhea 142 directed reaction 20374 and family (source version: Rhea 142, 2026-09-02; SHA256 is the full compressed official RDF gzip)RHEA:57493Rhea 142 directed reaction 57493 and family (source version: Rhea 142, 2026-09-02; SHA256 is the full compressed official RDF gzip)RHEA:57497Rhea 142 directed reaction 57497 and family (source version: Rhea 142, 2026-09-02; SHA256 is the full compressed official RDF gzip)UniProtKB:P27550Acetyl-coenzyme A synthetase (source version: UniProt 2026_03; 02-September-2026; complete JSON body)UniProtKB:P316602-methylcitrate synthase (source version: UniProt 2026_03; 02-September-2026; complete JSON body)UniProtKB:P36683Aconitate hydratase B (source version: UniProt 2026_03; 02-September-2026; complete JSON body)UniProtKB:P772432-methylcitrate dehydratase (source version: UniProt 2026_03; 02-September-2026; complete JSON body)UniProtKB:P77495Propionate--CoA ligase (source version: UniProt 2026_03; 02-September-2026; complete JSON body)UniProtKB:P775412-methylisocitrate lyase (source version: UniProt 2026_03; 02-September-2026; complete JSON body)
Curation history
- codex
- CREATE — Curated complete MetaCyc:PWY0-42 pathway network
Complete five-reaction native boundary; approved generic Rhea reactions represent unresolved methylcitrate stereochemistry explicitly. Acs/PrpE, PrpD metal and AcnB assembly limitations remain. Addresses the uncertainty-representation option of issue 332, pending independent review. Record SHA256 ea0940ee8eeb80d6552bed44e7afeeed4167866c919a291b750998997476745b. Evidence bodies, exact replays and source dispositions are retained in research/pathway_additions/2026-10-11-next-195. Shared authority integration, generated pages, full local gates and independent scientific reviews are subsequent checks; this CREATE event does not claim their completion.
- CREATE — Curated complete MetaCyc:PWY0-42 pathway network
- codex
- EDIT — Attach exact PrpD metal-conflict evidence to its pathway edge
Addressed finding methylcitrate-prpd-metal-conflict-source-attribution from initial review20261011T061951Z. Edge036 now separately cites the retained native G6199-MONOMER conflict comment and PMID11782506 unstable-cluster abstract; description is scoped to those source facts. Initial target and author inputs are archived under research/pathway_additions/2026-10-11-next-195/initial-review-inputs/propanoyl. Final YAML SHA256 0ccbcbcee61777f9f3265f5dec8c19ad5ce2ccf6051b54afe36fd1ed3bde40b7; 41 edges and 77 evidence. Nodes, reaction chemistry and no-obligatory-metal decision remain unchanged. Author source regression/replay, independent successor and final full corpus gates verify the change separately; unresolved absolute stereochemistry is retained.
- EDIT — Attach exact PrpD metal-conflict evidence to its pathway edge