Ethylmalonyl pathway

KEGG:M00373

The complete 14-reaction KEGG M00373 ethylmalonyl pathway assimilates three acetyl-CoA plus CO2 and bicarbonate into malate and succinyl-CoA. All twelve mandatory orthology groups are retained, including both propionyl-CoA carboxylase subunits and the complete propionyl branch. Experimental protein scope is Cereibacter sphaeroides 2.4.1/DSM158, historically Rhodobacter sphaeroides; AM1 studies provide separately scoped route and terminal-chemistry corroboration. Mcl2 hydrolysis terminates the malate branch without ATP formation. The native MetaCyc PWY-5741 ATP-forming terminal ligase conflicts with this chemistry, so the two pathway identifiers are not exact-mapped. Native CPD-9409 has an older stereochemical conflict; current Rhea/ChEBI beta-methylmalyl chemistry is retained. The R-specific hydroxybutyryl-CoA branch follows the issued module and primary R. sphaeroides evidence; AM1's figure versus assay R/S wording disagreement is not silently resolved. Rhea's whole-ETF redox states are a formal equation. The cited ACAD-family two-ETF mechanism is consistent with observed Mcd ETF semiquinone formation; the Mcd assays do not directly measure its two-ETF microscopic stoichiometry. D3JV03 exactly matches the deposited native 548-aa Mcd coding product; purification tags have separate construct scope; the 555-aa Q3J5V7 counterpart has seven extra N-terminal residues, with no processing explanation inferred. Reviewed Ecm/Mcd homodimer annotations, inferred PCC/MCM assemblies, alternative metal assay conditions and Mcl2's unresolved dimer/trimer are distinguished in evidence. PccR indirectly controls the PCC step through pccB transcription. Exact PhaB and crotonase protein assignments remain unresolved; this does not omit their chemical reactions. No upstream acetate activation, downstream TCA/serine reactions, engineered Mco chemistry or guessed regulator ligand is added.

Pathway type

acetyl coa assimilation

Organism scope

Cereibacter sphaeroides 2.4.1 NCBITaxon:272943

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Pathway network

65 nodes · 105 asserted directed edges

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Cereibacter sphaeroides 2.4.1 `NCBITaxon:272943`	taxon
water `CHEBI:15377`	small molecule
hydron `CHEBI:15378`	small molecule
(S)-malate(2-) `CHEBI:15589`	small molecule
carbon dioxide `CHEBI:16526`	small molecule
hydrogencarbonate `CHEBI:17544`	small molecule
ATP(4-) `CHEBI:30616`	small molecule
glyoxylate `CHEBI:36655`	small molecule
hydrogenphosphate `CHEBI:43474`	small molecule
acetoacetyl-CoA(4-) `CHEBI:57286`	small molecule
coenzyme A(4-) `CHEBI:57287`	small molecule
acetyl-CoA(4-) `CHEBI:57288`	small molecule
succinyl-CoA(5-) `CHEBI:57292`	small molecule
(R)-3-hydroxybutanoyl-CoA(4-) `CHEBI:57315`	small molecule
(3S)-3-carboxy-3-hydroxypropanoyl-CoA(5-) `CHEBI:57317`	small molecule
(R)-methylmalonyl-CoA(5-) `CHEBI:57326`	small molecule
(S)-methylmalonyl-CoA(5-) `CHEBI:57327`	small molecule
crotonoyl-CoA(4-) `CHEBI:57332`	small molecule
propionyl-CoA(4-) `CHEBI:57392`	small molecule
NADPH(4-) `CHEBI:57783`	small molecule
NADP(3-) `CHEBI:58349`	small molecule
(S)-ethylmalonyl-CoA(5-) `CHEBI:60909`	small molecule
L-erythro-3-methylmalyl-CoA(5-) `CHEBI:75634`	small molecule
mesaconyl-CoA(5-) `CHEBI:75635`	small molecule
(2S)-methylsuccinyl-CoA(5-) `CHEBI:84866`	small molecule
(R)-ethylmalonyl-CoA(5-) `CHEBI:85316`	small molecule
ADP(3-) `CHEBI:456216`	small molecule
cobamamide `CHEBI:18408`	cofactor
magnesium(2+) `CHEBI:18420`	cofactor
manganese(2+) `CHEBI:29035`	cofactor
cobalt(2+) `CHEBI:48828`	cofactor
biotinate `CHEBI:57586`	cofactor
FAD(3-) `CHEBI:57692`	cofactor
oxidized [electron-transfer flavoprotein] `RHEA-COMP:10685`	protein
reduced [electron-transfer flavoprotein] `RHEA-COMP:10686`	protein
Acetyl-CoA C-acetyltransferase `UniProtKB:Q3IZW1`	protein
Crotonyl-CoA carboxylase/reductase `UniProtKB:Q3IZ91`	protein
Ethylmalonyl-CoA/methylmalonyl-CoA epimerase `UniProtKB:Q3IZP4`	protein
Ethylmalonyl-CoA mutase `UniProtKB:Q3IZ90`	protein
(2S)-methylsuccinyl-CoA dehydrogenase `UniProtKB:D3JV03`	protein
Mesaconyl-CoA hydratase `UniProtKB:Q3IZ78`	protein
L-malyl-CoA/beta-methylmalyl-CoA lyase `UniProtKB:Q3J5L6`	protein
(3S)-malyl-CoA thioesterase `UniProtKB:D3JV05`	protein
propionyl-CoA carboxylase `UniProtKB:Q3J4D9`	protein
Propionyl-CoA carboxylase beta chain `UniProtKB:Q3J4E3`	protein
Methylmalonyl-CoA mutase `UniProtKB:Q3J4D7`	protein
Propionyl-CoA carboxylase regulator `UniProtKB:Q3J4E6`	protein
crotonyl-CoA carboxylase/reductase `MetaCyc:CPLX-7544`	complex
(2S)-methylsuccinyl-CoA dehydrogenase `MetaCyc:CPLX-8971`	complex
(2R)-ethylmalonyl-CoA mutase `MetaCyc:CPLX-8972`	complex
L-malyl-CoA/β-methylmalyl-CoA lyase `MetaCyc:CPLX-9178`	complex
2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	reaction	left to right
acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	reaction	right to left
(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	reaction	left to right
(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	reaction	right to left
(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	reaction	right to left
(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	reaction	left to right
(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	reaction	left to right
2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	reaction	right to left
(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	reaction	left to right
glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	reaction	right to left
(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	reaction	left to right
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	reaction	left to right
(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	reaction	right to left
(R)-methylmalonyl-CoA => succinyl-CoA `RHEA:22889`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	part_of All 14 issued module reactions are retained; K00626 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R00238 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R00238; ORTHOLOGY K00626; DEFINITION` RHEA:21037 Source assertion: Approved directional equation: 2 acetyl-CoA => acetoacetyl-CoA + CoA Source location `RDF subject http://rdf.rhea-db.org/21037; rh:equation; rh:status`
acetyl-CoA(4-) `CHEBI:57288`	consumes Stoichiometric coefficient 2.	2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	RHEA:21037 Source assertion: The approved reaction consumes 2 acetyl-CoA; this is the whole participant identified as CHEBI:57288. Source location `RDF 21037 rh:substrates http://rdf.rhea-db.org/21036_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4271; rh:contains2`
2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	produces Stoichiometric coefficient 1.	acetoacetyl-CoA(4-) `CHEBI:57286`	RHEA:21037 Source assertion: The approved reaction produces 1 acetoacetyl-CoA; this is the whole participant identified as CHEBI:57286. Source location `RDF 21037 rh:products http://rdf.rhea-db.org/21036_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4872; rh:contains1`
2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	produces Stoichiometric coefficient 1.	coenzyme A(4-) `CHEBI:57287`	RHEA:21037 Source assertion: The approved reaction produces 1 CoA; this is the whole participant identified as CHEBI:57287. Source location `RDF 21037 rh:products http://rdf.rhea-db.org/21036_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1264; rh:contains1`
acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	part_of All 14 issued module reactions are retained; K00023 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R01977 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R01977; ORTHOLOGY K00023; DEFINITION` RHEA:45798 Source assertion: Approved directional equation: acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) Source location `RDF subject http://rdf.rhea-db.org/45798; rh:equation; rh:status`
acetoacetyl-CoA(4-) `CHEBI:57286`	consumes Stoichiometric coefficient 1.	acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	RHEA:45798 Source assertion: The approved reaction consumes 1 acetoacetyl-CoA; this is the whole participant identified as CHEBI:57286. Source location `RDF 45798 rh:substrates http://rdf.rhea-db.org/45796_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4872; rh:contains1`
NADPH(4-) `CHEBI:57783`	consumes Stoichiometric coefficient 1.	acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	RHEA:45798 Source assertion: The approved reaction consumes 1 NADPH; this is the whole participant identified as CHEBI:57783. Source location `RDF 45798 rh:substrates http://rdf.rhea-db.org/45796_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3438; rh:contains1`
hydron `CHEBI:15378`	consumes Stoichiometric coefficient 1.	acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	RHEA:45798 Source assertion: The approved reaction consumes 1 H(+); this is the whole participant identified as CHEBI:15378. Source location `RDF 45798 rh:substrates http://rdf.rhea-db.org/45796_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3249; rh:contains1`
acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	produces Stoichiometric coefficient 1.	(R)-3-hydroxybutanoyl-CoA(4-) `CHEBI:57315`	RHEA:45798 Source assertion: The approved reaction produces 1 (3R)-3-hydroxybutanoyl-CoA; this is the whole participant identified as CHEBI:57315. Source location `RDF 45798 rh:products http://rdf.rhea-db.org/45796_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4693; rh:contains1`
acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	produces Stoichiometric coefficient 1.	NADP(3-) `CHEBI:58349`	RHEA:45798 Source assertion: The approved reaction produces 1 NADP(+); this is the whole participant identified as CHEBI:58349. Source location `RDF 45798 rh:products http://rdf.rhea-db.org/45796_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_5188; rh:contains1`
(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	part_of All 14 issued module reactions are retained; K17865 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R03027 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R03027; ORTHOLOGY K17865; DEFINITION` RHEA:17850 Source assertion: Approved directional equation: (3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O Source location `RDF subject http://rdf.rhea-db.org/17850; rh:equation; rh:status`
(R)-3-hydroxybutanoyl-CoA(4-) `CHEBI:57315`	consumes Stoichiometric coefficient 1.	(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	RHEA:17850 Source assertion: The approved reaction consumes 1 (3R)-3-hydroxybutanoyl-CoA; this is the whole participant identified as CHEBI:57315. Source location `RDF 17850 rh:substrates http://rdf.rhea-db.org/17849_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4693; rh:contains1`
(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	produces Stoichiometric coefficient 1.	crotonoyl-CoA(4-) `CHEBI:57332`	RHEA:17850 Source assertion: The approved reaction produces 1 (2E)-butenoyl-CoA; this is the whole participant identified as CHEBI:57332. Source location `RDF 17850 rh:products http://rdf.rhea-db.org/17849_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_2633; rh:contains1`
(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	produces Stoichiometric coefficient 1.	water `CHEBI:15377`	RHEA:17850 Source assertion: The approved reaction produces 1 H2O; this is the whole participant identified as CHEBI:15377. Source location `RDF 17850 rh:products http://rdf.rhea-db.org/17849_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1283; rh:contains1`
(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	part_of All 14 issued module reactions are retained; K14446 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R09291 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R09291; ORTHOLOGY K14446; DEFINITION` RHEA:28084 Source assertion: Approved directional equation: (2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) Source location `RDF subject http://rdf.rhea-db.org/28084; rh:equation; rh:status`
crotonoyl-CoA(4-) `CHEBI:57332`	consumes Stoichiometric coefficient 1.	(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	RHEA:28084 Source assertion: The approved reaction consumes 1 (2E)-butenoyl-CoA; this is the whole participant identified as CHEBI:57332. Source location `RDF 28084 rh:substrates http://rdf.rhea-db.org/28082_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_2633; rh:contains1`
carbon dioxide `CHEBI:16526`	consumes Stoichiometric coefficient 1.	(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	RHEA:28084 Source assertion: The approved reaction consumes 1 CO2; this is the whole participant identified as CHEBI:16526. Source location `RDF 28084 rh:substrates http://rdf.rhea-db.org/28082_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4391; rh:contains1`
NADPH(4-) `CHEBI:57783`	consumes Stoichiometric coefficient 1.	(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	RHEA:28084 Source assertion: The approved reaction consumes 1 NADPH; this is the whole participant identified as CHEBI:57783. Source location `RDF 28084 rh:substrates http://rdf.rhea-db.org/28082_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3438; rh:contains1`
(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	produces Stoichiometric coefficient 1.	(S)-ethylmalonyl-CoA(5-) `CHEBI:60909`	RHEA:28084 Source assertion: The approved reaction produces 1 (2S)-ethylmalonyl-CoA; this is the whole participant identified as CHEBI:60909. Source location `RDF 28084 rh:products http://rdf.rhea-db.org/28082_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_6333; rh:contains1`
(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	produces Stoichiometric coefficient 1.	NADP(3-) `CHEBI:58349`	RHEA:28084 Source assertion: The approved reaction produces 1 NADP(+); this is the whole participant identified as CHEBI:58349. Source location `RDF 28084 rh:products http://rdf.rhea-db.org/28082_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_5188; rh:contains1`
(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	part_of All 14 issued module reactions are retained; K05606 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R09979 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R09979; ORTHOLOGY K05606; DEFINITION` RHEA:59730 Source assertion: Approved directional equation: (2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA Source location `RDF subject http://rdf.rhea-db.org/59730; rh:equation; rh:status`
(S)-ethylmalonyl-CoA(5-) `CHEBI:60909`	consumes Stoichiometric coefficient 1.	(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	RHEA:59730 Source assertion: The approved reaction consumes 1 (2S)-ethylmalonyl-CoA; this is the whole participant identified as CHEBI:60909. Source location `RDF 59730 rh:substrates http://rdf.rhea-db.org/59728_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_6333; rh:contains1`
(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	produces Stoichiometric coefficient 1.	(R)-ethylmalonyl-CoA(5-) `CHEBI:85316`	RHEA:59730 Source assertion: The approved reaction produces 1 (2R)-ethylmalonyl-CoA; this is the whole participant identified as CHEBI:85316. Source location `RDF 59730 rh:products http://rdf.rhea-db.org/59728_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_11275; rh:contains1`
(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	part_of All 14 issued module reactions are retained; K14447 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R09292 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R09292; ORTHOLOGY K14447; DEFINITION` RHEA:45577 Source assertion: Approved directional equation: (2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA Source location `RDF subject http://rdf.rhea-db.org/45577; rh:equation; rh:status`
(R)-ethylmalonyl-CoA(5-) `CHEBI:85316`	consumes Stoichiometric coefficient 1.	(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	RHEA:45577 Source assertion: The approved reaction consumes 1 (2R)-ethylmalonyl-CoA; this is the whole participant identified as CHEBI:85316. Source location `RDF 45577 rh:substrates http://rdf.rhea-db.org/45576_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_11275; rh:contains1`
(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	produces Stoichiometric coefficient 1.	(2S)-methylsuccinyl-CoA(5-) `CHEBI:84866`	RHEA:45577 Source assertion: The approved reaction produces 1 (2S)-methylsuccinyl-CoA; this is the whole participant identified as CHEBI:84866. Source location `RDF 45577 rh:products http://rdf.rhea-db.org/45576_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_11065; rh:contains1`
(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	part_of All 14 issued module reactions are retained; K14448 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R09293 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R09293; ORTHOLOGY K14448; DEFINITION` RHEA:45029 Source assertion: Approved directional equation: (2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] Source location `RDF subject http://rdf.rhea-db.org/45029; rh:equation; rh:status`
(2S)-methylsuccinyl-CoA(5-) `CHEBI:84866`	consumes Stoichiometric coefficient 1.	(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	RHEA:45029 Source assertion: The approved reaction consumes 1 (2S)-methylsuccinyl-CoA; this is the whole participant identified as CHEBI:84866. Source location `RDF 45029 rh:substrates http://rdf.rhea-db.org/45028_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_11065; rh:contains1`
oxidized [electron-transfer flavoprotein] `RHEA-COMP:10685`	consumes Stoichiometric coefficient 1. Whole ETF protein redox state in the formal Rhea equation. The ACAD-family two-ETF mechanism is consistent with Mcd ETF semiquinone formation; these Mcd assays do not directly measure two-ETF microscopic stoichiometry. See emc-084 for primary scope.	(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	RHEA:45029 Source assertion: The approved reaction consumes 1 oxidized [electron-transfer flavoprotein]; this is the whole participant identified as RHEA-COMP:10685. Source location `RDF 45029 rh:substrates http://rdf.rhea-db.org/45028_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_10685; rh:contains1`
hydron `CHEBI:15378`	consumes Stoichiometric coefficient 1.	(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	RHEA:45029 Source assertion: The approved reaction consumes 1 H(+); this is the whole participant identified as CHEBI:15378. Source location `RDF 45029 rh:substrates http://rdf.rhea-db.org/45028_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3249; rh:contains1`
(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	produces Stoichiometric coefficient 1.	mesaconyl-CoA(5-) `CHEBI:75635`	RHEA:45029 Source assertion: The approved reaction produces 1 2-methylfumaryl-CoA; this is the whole participant identified as CHEBI:75635. Source location `RDF 45029 rh:products http://rdf.rhea-db.org/45028_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_8546; rh:contains1`
(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	produces Stoichiometric coefficient 1. Whole ETF protein redox state in the formal Rhea equation. The ACAD-family two-ETF mechanism is consistent with Mcd ETF semiquinone formation; these Mcd assays do not directly measure two-ETF microscopic stoichiometry. See emc-084 for primary scope.	reduced [electron-transfer flavoprotein] `RHEA-COMP:10686`	RHEA:45029 Source assertion: The approved reaction produces 1 reduced [electron-transfer flavoprotein]; this is the whole participant identified as RHEA-COMP:10686. Source location `RDF 45029 rh:products http://rdf.rhea-db.org/45028_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_10686; rh:contains1`
2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	part_of All 14 issued module reactions are retained; K14449 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R05076 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R05076; ORTHOLOGY K14449; DEFINITION` RHEA:38265 Source assertion: Approved directional equation: 2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA Source location `RDF subject http://rdf.rhea-db.org/38265; rh:equation; rh:status`
mesaconyl-CoA(5-) `CHEBI:75635`	consumes Stoichiometric coefficient 1.	2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	RHEA:38265 Source assertion: The approved reaction consumes 1 2-methylfumaryl-CoA; this is the whole participant identified as CHEBI:75635. Source location `RDF 38265 rh:substrates http://rdf.rhea-db.org/38263_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_8546; rh:contains1`
water `CHEBI:15377`	consumes Stoichiometric coefficient 1.	2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	RHEA:38265 Source assertion: The approved reaction consumes 1 H2O; this is the whole participant identified as CHEBI:15377. Source location `RDF 38265 rh:substrates http://rdf.rhea-db.org/38263_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1283; rh:contains1`
2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	produces Stoichiometric coefficient 1.	L-erythro-3-methylmalyl-CoA(5-) `CHEBI:75634`	RHEA:38265 Source assertion: The approved reaction produces 1 (2R,3S)-beta-methylmalyl-CoA; this is the whole participant identified as CHEBI:75634. Source location `RDF 38265 rh:products http://rdf.rhea-db.org/38263_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_8545; rh:contains1`
(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	part_of All 14 issued module reactions are retained; K08691 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R00934 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R00934; ORTHOLOGY K08691; DEFINITION` RHEA:38260 Source assertion: Approved directional equation: (2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate Source location `RDF subject http://rdf.rhea-db.org/38260; rh:equation; rh:status`
L-erythro-3-methylmalyl-CoA(5-) `CHEBI:75634`	consumes Stoichiometric coefficient 1.	(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	RHEA:38260 Source assertion: The approved reaction consumes 1 (2R,3S)-beta-methylmalyl-CoA; this is the whole participant identified as CHEBI:75634. Source location `RDF 38260 rh:substrates http://rdf.rhea-db.org/38259_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_8545; rh:contains1`
(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	produces Stoichiometric coefficient 1.	propionyl-CoA(4-) `CHEBI:57392`	RHEA:38260 Source assertion: The approved reaction produces 1 propanoyl-CoA; this is the whole participant identified as CHEBI:57392. Source location `RDF 38260 rh:products http://rdf.rhea-db.org/38259_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3421; rh:contains1`
(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	produces Stoichiometric coefficient 1.	glyoxylate `CHEBI:36655`	RHEA:38260 Source assertion: The approved reaction produces 1 glyoxylate; this is the whole participant identified as CHEBI:36655. Source location `RDF 38260 rh:products http://rdf.rhea-db.org/38259_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3124; rh:contains1`
glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	part_of All 14 issued module reactions are retained; K08691 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R00473 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R00473; ORTHOLOGY K08691; DEFINITION` RHEA:16631 Source assertion: Approved directional equation: glyoxylate + acetyl-CoA => (S)-malyl-CoA Source location `RDF subject http://rdf.rhea-db.org/16631; rh:equation; rh:status`
glyoxylate `CHEBI:36655`	consumes Stoichiometric coefficient 1.	glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	RHEA:16631 Source assertion: The approved reaction consumes 1 glyoxylate; this is the whole participant identified as CHEBI:36655. Source location `RDF 16631 rh:substrates http://rdf.rhea-db.org/16629_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3124; rh:contains1`
acetyl-CoA(4-) `CHEBI:57288`	consumes Stoichiometric coefficient 1.	glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	RHEA:16631 Source assertion: The approved reaction consumes 1 acetyl-CoA; this is the whole participant identified as CHEBI:57288. Source location `RDF 16631 rh:substrates http://rdf.rhea-db.org/16629_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4271; rh:contains1`
glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	produces Stoichiometric coefficient 1.	(3S)-3-carboxy-3-hydroxypropanoyl-CoA(5-) `CHEBI:57317`	RHEA:16631 Source assertion: The approved reaction produces 1 (S)-malyl-CoA; this is the whole participant identified as CHEBI:57317. Source location `RDF 16631 rh:products http://rdf.rhea-db.org/16629_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3610; rh:contains1`
(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	part_of All 14 issued module reactions are retained; K14451 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R10612 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R10612; ORTHOLOGY K14451; DEFINITION` RHEA:38292 Source assertion: Approved directional equation: (S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) Source location `RDF subject http://rdf.rhea-db.org/38292; rh:equation; rh:status`
(3S)-3-carboxy-3-hydroxypropanoyl-CoA(5-) `CHEBI:57317`	consumes Stoichiometric coefficient 1.	(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	RHEA:38292 Source assertion: The approved reaction consumes 1 (S)-malyl-CoA; this is the whole participant identified as CHEBI:57317. Source location `RDF 38292 rh:substrates http://rdf.rhea-db.org/38291_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3610; rh:contains1`
water `CHEBI:15377`	consumes Stoichiometric coefficient 1.	(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	RHEA:38292 Source assertion: The approved reaction consumes 1 H2O; this is the whole participant identified as CHEBI:15377. Source location `RDF 38292 rh:substrates http://rdf.rhea-db.org/38291_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1283; rh:contains1`
(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	produces Stoichiometric coefficient 1.	(S)-malate(2-) `CHEBI:15589`	RHEA:38292 Source assertion: The approved reaction produces 1 (S)-malate; this is the whole participant identified as CHEBI:15589. Source location `RDF 38292 rh:products http://rdf.rhea-db.org/38291_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3953; rh:contains1`
(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	produces Stoichiometric coefficient 1.	coenzyme A(4-) `CHEBI:57287`	RHEA:38292 Source assertion: The approved reaction produces 1 CoA; this is the whole participant identified as CHEBI:57287. Source location `RDF 38292 rh:products http://rdf.rhea-db.org/38291_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1264; rh:contains1`
(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	produces Stoichiometric coefficient 1.	hydron `CHEBI:15378`	RHEA:38292 Source assertion: The approved reaction produces 1 H(+); this is the whole participant identified as CHEBI:15378. Source location `RDF 38292 rh:products http://rdf.rhea-db.org/38291_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3249; rh:contains1`
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	part_of All 14 issued module reactions are retained; K01965+K01966 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R01859 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R01859; ORTHOLOGY K01965+K01966; DEFINITION` RHEA:23721 Source assertion: Approved directional equation: propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) Source location `RDF subject http://rdf.rhea-db.org/23721; rh:equation; rh:status`
propionyl-CoA(4-) `CHEBI:57392`	consumes Stoichiometric coefficient 1.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	RHEA:23721 Source assertion: The approved reaction consumes 1 propanoyl-CoA; this is the whole participant identified as CHEBI:57392. Source location `RDF 23721 rh:substrates http://rdf.rhea-db.org/23720_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3421; rh:contains1`
hydrogencarbonate `CHEBI:17544`	consumes Stoichiometric coefficient 1.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	RHEA:23721 Source assertion: The approved reaction consumes 1 hydrogencarbonate; this is the whole participant identified as CHEBI:17544. Source location `RDF 23721 rh:substrates http://rdf.rhea-db.org/23720_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1123; rh:contains1`
ATP(4-) `CHEBI:30616`	consumes Stoichiometric coefficient 1.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	RHEA:23721 Source assertion: The approved reaction consumes 1 ATP; this is the whole participant identified as CHEBI:30616. Source location `RDF 23721 rh:substrates http://rdf.rhea-db.org/23720_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_6372; rh:contains1`
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	produces Stoichiometric coefficient 1.	(S)-methylmalonyl-CoA(5-) `CHEBI:57327`	RHEA:23721 Source assertion: The approved reaction produces 1 (S)-methylmalonyl-CoA; this is the whole participant identified as CHEBI:57327. Source location `RDF 23721 rh:products http://rdf.rhea-db.org/23720_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_2780; rh:contains1`
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	produces Stoichiometric coefficient 1.	ADP(3-) `CHEBI:456216`	RHEA:23721 Source assertion: The approved reaction produces 1 ADP; this is the whole participant identified as CHEBI:456216. Source location `RDF 23721 rh:products http://rdf.rhea-db.org/23720_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_2710; rh:contains1`
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	produces Stoichiometric coefficient 1.	hydrogenphosphate `CHEBI:43474`	RHEA:23721 Source assertion: The approved reaction produces 1 phosphate; this is the whole participant identified as CHEBI:43474. Source location `RDF 23721 rh:products http://rdf.rhea-db.org/23720_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_5518; rh:contains1`
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	produces Stoichiometric coefficient 1.	hydron `CHEBI:15378`	RHEA:23721 Source assertion: The approved reaction produces 1 H(+); this is the whole participant identified as CHEBI:15378. Source location `RDF 23721 rh:products http://rdf.rhea-db.org/23720_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_3249; rh:contains1`
(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	part_of All 14 issued module reactions are retained; K05606 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R02765 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R02765; ORTHOLOGY K05606; DEFINITION` RHEA:20555 Source assertion: Approved directional equation: (S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA Source location `RDF subject http://rdf.rhea-db.org/20555; rh:equation; rh:status`
(S)-methylmalonyl-CoA(5-) `CHEBI:57327`	consumes Stoichiometric coefficient 1.	(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	RHEA:20555 Source assertion: The approved reaction consumes 1 (S)-methylmalonyl-CoA; this is the whole participant identified as CHEBI:57327. Source location `RDF 20555 rh:substrates http://rdf.rhea-db.org/20553_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_2780; rh:contains1`
(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	produces Stoichiometric coefficient 1.	(R)-methylmalonyl-CoA(5-) `CHEBI:57326`	RHEA:20555 Source assertion: The approved reaction produces 1 (R)-methylmalonyl-CoA; this is the whole participant identified as CHEBI:57326. Source location `RDF 20555 rh:products http://rdf.rhea-db.org/20553_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1391; rh:contains1`
(R)-methylmalonyl-CoA => succinyl-CoA `RHEA:22889`	part_of All 14 issued module reactions are retained; K01847 is the module orthology requirement.	`KEGG:M00373`	KEGG:M00373 Source assertion: M00373 REACTION row R00833 is included in the ethylmalonyl pathway; the complete DEFINITION has 12 required groups and 13 KOs, with K01965+K01966 an obligatory pair. Source location `ENTRY M00373 / REACTION R00833; ORTHOLOGY K01847; DEFINITION` RHEA:22889 Source assertion: Approved directional equation: (R)-methylmalonyl-CoA => succinyl-CoA Source location `RDF subject http://rdf.rhea-db.org/22889; rh:equation; rh:status`
(R)-methylmalonyl-CoA(5-) `CHEBI:57326`	consumes Stoichiometric coefficient 1.	(R)-methylmalonyl-CoA => succinyl-CoA `RHEA:22889`	RHEA:22889 Source assertion: The approved reaction consumes 1 (R)-methylmalonyl-CoA; this is the whole participant identified as CHEBI:57326. Source location `RDF 22889 rh:substrates http://rdf.rhea-db.org/22888_L; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_1391; rh:contains1`
(R)-methylmalonyl-CoA => succinyl-CoA `RHEA:22889`	produces Stoichiometric coefficient 1.	succinyl-CoA(5-) `CHEBI:57292`	RHEA:22889 Source assertion: The approved reaction produces 1 succinyl-CoA; this is the whole participant identified as CHEBI:57292. Source location `RDF 22889 rh:products http://rdf.rhea-db.org/22888_R; rh:contains participant / rh:compound http://rdf.rhea-db.org/Compound_4684; rh:contains1`
2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	provides_input_for Material flow through acetoacetyl-CoA(4-); no enzyme channeling or physical association is implied.	acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	RHEA:21037 Source assertion: This reaction produces acetoacetyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/21037 rh:products` RHEA:45798 Source assertion: This reaction consumes acetoacetyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/45798 rh:substrates`
acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) `RHEA:45798`	provides_input_for Material flow through (R)-3-hydroxybutanoyl-CoA(4-); no enzyme channeling or physical association is implied.	(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	RHEA:45798 Source assertion: This reaction produces (R)-3-hydroxybutanoyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/45798 rh:products` RHEA:17850 Source assertion: This reaction consumes (R)-3-hydroxybutanoyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/17850 rh:substrates`
(3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O `RHEA:17850`	provides_input_for Material flow through crotonoyl-CoA(4-); no enzyme channeling or physical association is implied.	(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	RHEA:17850 Source assertion: This reaction produces crotonoyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/17850 rh:products` RHEA:28084 Source assertion: This reaction consumes crotonoyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/28084 rh:substrates`
(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	provides_input_for Material flow through (S)-ethylmalonyl-CoA(5-); no enzyme channeling or physical association is implied.	(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	RHEA:28084 Source assertion: This reaction produces (S)-ethylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/28084 rh:products` RHEA:59730 Source assertion: This reaction consumes (S)-ethylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/59730 rh:substrates`
(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	provides_input_for Material flow through (R)-ethylmalonyl-CoA(5-); no enzyme channeling or physical association is implied.	(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	RHEA:59730 Source assertion: This reaction produces (R)-ethylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/59730 rh:products` RHEA:45577 Source assertion: This reaction consumes (R)-ethylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/45577 rh:substrates`
(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	provides_input_for Material flow through (2S)-methylsuccinyl-CoA(5-); no enzyme channeling or physical association is implied.	(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	RHEA:45577 Source assertion: This reaction produces (2S)-methylsuccinyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/45577 rh:products` RHEA:45029 Source assertion: This reaction consumes (2S)-methylsuccinyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/45029 rh:substrates`
(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	provides_input_for Material flow through mesaconyl-CoA(5-); no enzyme channeling or physical association is implied.	2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	RHEA:45029 Source assertion: This reaction produces mesaconyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/45029 rh:products` RHEA:38265 Source assertion: This reaction consumes mesaconyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/38265 rh:substrates`
2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	provides_input_for Material flow through L-erythro-3-methylmalyl-CoA(5-); no enzyme channeling or physical association is implied.	(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	RHEA:38265 Source assertion: This reaction produces L-erythro-3-methylmalyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/38265 rh:products` RHEA:38260 Source assertion: This reaction consumes L-erythro-3-methylmalyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/38260 rh:substrates`
(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	provides_input_for Material flow through glyoxylate; no enzyme channeling or physical association is implied.	glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	RHEA:38260 Source assertion: This reaction produces glyoxylate. Source location `RDF subject http://rdf.rhea-db.org/38260 rh:products` RHEA:16631 Source assertion: This reaction consumes glyoxylate. Source location `RDF subject http://rdf.rhea-db.org/16631 rh:substrates`
glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	provides_input_for Material flow through (3S)-3-carboxy-3-hydroxypropanoyl-CoA(5-); no enzyme channeling or physical association is implied.	(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	RHEA:16631 Source assertion: This reaction produces (3S)-3-carboxy-3-hydroxypropanoyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/16631 rh:products` RHEA:38292 Source assertion: This reaction consumes (3S)-3-carboxy-3-hydroxypropanoyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/38292 rh:substrates`
(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	provides_input_for Material flow through propionyl-CoA(4-); no enzyme channeling or physical association is implied.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	RHEA:38260 Source assertion: This reaction produces propionyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/38260 rh:products` RHEA:23721 Source assertion: This reaction consumes propionyl-CoA(4-). Source location `RDF subject http://rdf.rhea-db.org/23721 rh:substrates`
propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	provides_input_for Material flow through (S)-methylmalonyl-CoA(5-); no enzyme channeling or physical association is implied.	(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	RHEA:23721 Source assertion: This reaction produces (S)-methylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/23721 rh:products` RHEA:20555 Source assertion: This reaction consumes (S)-methylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/20555 rh:substrates`
(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	provides_input_for Material flow through (R)-methylmalonyl-CoA(5-); no enzyme channeling or physical association is implied.	(R)-methylmalonyl-CoA => succinyl-CoA `RHEA:22889`	RHEA:20555 Source assertion: This reaction produces (R)-methylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/20555 rh:products` RHEA:22889 Source assertion: This reaction consumes (R)-methylmalonyl-CoA(5-). Source location `RDF subject http://rdf.rhea-db.org/22889 rh:substrates`
crotonyl-CoA carboxylase/reductase `MetaCyc:CPLX-7544`	has_part Native species-level assembly contains 2 identical subunits. Native component xref resolves to the selected current accession (or its issued secondary accession).	Crotonyl-CoA carboxylase/reductase `UniProtKB:Q3IZ91`	MetaCyc:CPLX-7544 Source assertion: Native MetaCyc:CPLX-7544 lists MONOMER-13592 with coefficient 2 and species TAX-1063. Source location `XML /ptools-xml/Protein[@frameid='CPLX-7544']/component[Protein/@frameid='MONOMER-13592']/coefficient; species/Organism/@frameid` UniProtKB:Q3IZ91 Source assertion: Homodimer; evidence ECO:0000269. Source location `/comments/6; /primaryAccession; /sequence; /secondaryAccessions`
(2S)-methylsuccinyl-CoA dehydrogenase `MetaCyc:CPLX-8971`	has_part Native species-level assembly contains 2 identical subunits. Native component xref resolves to the selected current accession (or its issued secondary accession). Homodimer is retained as reviewed database evidence; the original cited paper was inspected only as an abstract.	(2S)-methylsuccinyl-CoA dehydrogenase `UniProtKB:D3JV03`	MetaCyc:CPLX-8971 Source assertion: Native MetaCyc:CPLX-8971 lists MONOMER-19169 with coefficient 2 and species TAX-1063. Source location `XML /ptools-xml/Protein[@frameid='CPLX-8971']/component[Protein/@frameid='MONOMER-19169']/coefficient; species/Organism/@frameid` UniProtKB:D3JV03 Source assertion: Homodimer; evidence ECO:0000269. Source location `/comments/4; /primaryAccession; /sequence`
(2R)-ethylmalonyl-CoA mutase `MetaCyc:CPLX-8972`	has_part Native species-level assembly contains 2 identical subunits. Native component xref resolves to the selected current accession (or its issued secondary accession). Homodimer is retained as reviewed database evidence; the original cited paper was inspected only as an abstract.	Ethylmalonyl-CoA mutase `UniProtKB:Q3IZ90`	MetaCyc:CPLX-8972 Source assertion: Native MetaCyc:CPLX-8972 lists MONOMER-19170 with coefficient 2 and species TAX-1063. Source location `XML /ptools-xml/Protein[@frameid='CPLX-8972']/component[Protein/@frameid='MONOMER-19170']/coefficient; species/Organism/@frameid` UniProtKB:Q3IZ90 Source assertion: Homodimer; evidence ECO:0000269. Source location `/comments/4; /primaryAccession; /sequence; /secondaryAccessions`
L-malyl-CoA/β-methylmalyl-CoA lyase `MetaCyc:CPLX-9178`	has_part Native species-level assembly contains 6 identical subunits. Mcl1 exact strain/protein bridge comes from the 2010/2013 studies and matching deposited sequence; the native component has no UniProt xref.	L-malyl-CoA/beta-methylmalyl-CoA lyase `UniProtKB:Q3J5L6`	MetaCyc:CPLX-9178 Source assertion: Native MetaCyc:CPLX-9178 lists MONOMER-20104 with coefficient 6 and species TAX-1063. Source location `XML /ptools-xml/Protein[@frameid='CPLX-9178']/component[Protein/@frameid='MONOMER-20104']/coefficient; species/Organism/@frameid` UniProtKB:Q3J5L6 Source assertion: Homohexamer. Dimer of trimers; evidence ECO:0000269. Source location `/comments/7; /primaryAccession; /sequence; /secondaryAccessions` PMID:24206647 Source assertion: MCLR from R. sphaeroides 2.4.1 was expressed as an N-terminal His10-tagged construct; structural and gel-filtration results support a hexamer, a dimer of trimers. Source location `HTML section#sec7; section#sec9; section#sec18/p[2]; section#sec19/p[2]`
crotonyl-CoA carboxylase/reductase `MetaCyc:CPLX-7544`	catalyzes Catalysis by the assembled enzyme. Exact sequence bridges and source-specific evidence tiers are retained in the research ledger.	(2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) `RHEA:28084`	UniProtKB:Q3IZ91 Source assertion: The selected gene product is assigned this catalytic reaction with ECO:0000269 evidence; directional physiological use is scoped separately from database equation orientation. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1` MetaCyc:CPLX-7544 Source assertion: The native assembled protein lists its enzymatic-reaction association and described catalytic transformation. Source location `XML /ptools-xml/Protein/catalyzes; /ptools-xml/Protein/comment` PMID:17548827 Source assertion: Purified R. sphaeroides Ccr reductively carboxylates crotonyl-CoA with NADPH; CO2 is the reactive species and metal analysis found no bound metal. Source location `HTML section#sec4; section#sec16; section#sec24`
(2R)-ethylmalonyl-CoA mutase `MetaCyc:CPLX-8972`	catalyzes Catalysis by the assembled enzyme. Exact sequence bridges and source-specific evidence tiers are retained in the research ledger.	(2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA `RHEA:45577`	UniProtKB:Q3IZ90 Source assertion: The selected gene product is assigned this catalytic reaction with ECO:0000269 evidence; directional physiological use is scoped separately from database equation orientation. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1` MetaCyc:CPLX-8972 Source assertion: The native assembled protein lists its enzymatic-reaction association and described catalytic transformation. Source location `XML /ptools-xml/Protein/catalyzes; /ptools-xml/Protein/comment`
(2S)-methylsuccinyl-CoA dehydrogenase `MetaCyc:CPLX-8971`	catalyzes Catalysis by the assembled enzyme. Exact sequence bridges and source-specific evidence tiers are retained in the research ledger. D3JV03 matches the native 548-aa ADC44452.1 coding product, not purification tags. Its UniProt taxon is species1063; the original protein/CDS strain qualifier is 2.4.1. Q3J5V7 has seven extra N-terminal residues and is not substituted. The Rhea whole-ETF equation is a formal abstraction; observed Mcd ETF semiquinone formation is consistent with the cited ACAD-family mechanism, without directly measuring its two-ETF microscopic stoichiometry.	(2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] `RHEA:45029`	UniProtKB:D3JV03 Source assertion: The selected gene product is assigned this catalytic reaction with ECO:0000269 evidence; directional physiological use is scoped separately from database equation orientation. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1` MetaCyc:CPLX-8971 Source assertion: The native assembled protein lists its enzymatic-reaction association and described catalytic transformation. Source location `XML /ptools-xml/Protein/catalyzes; /ptools-xml/Protein/comment` NCBIProtein:ADC44452.1 Source assertion: The original versioned protein has 548 residues and source strain 2.4.1, with species taxon1063. Its entire sequence matches D3JV03; purification tags are outside this native sequence. Source location `XML /GBSet/GBSeq[GBSeq_accession-version='ADC44452.1']/GBSeq_sequence; GBSeq_feature-table/GBFeature[GBFeature_key='source']/GBFeature_quals/GBQualifier[GBQualifier_name='strain']` PMID:29283425 Source assertion: Wild-type Mcd uses ETF and forms ETF semiquinone. The Introduction describes the ACAD-family mechanism as two successive one-electron transfers to two ETFs, citing prior work. This is consistent with Mcd observations, not a direct measurement of two-ETF microscopic stoichiometry; engineered oxygen-using Mco variants are distinct. Source location `HTML section#sec1-molecules-23-00068/p[2]; section#sec2dot3-molecules-23-00068; section#sec4dot1-molecules-23-00068; section#molecules-23-00068-t001`
L-malyl-CoA/β-methylmalyl-CoA lyase `MetaCyc:CPLX-9178`	catalyzes Catalysis by the assembled enzyme. Exact sequence bridges and source-specific evidence tiers are retained in the research ledger.	(2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate `RHEA:38260`	UniProtKB:Q3J5L6 Source assertion: The selected gene product is assigned this catalytic reaction with ECO:0000269 evidence; directional physiological use is scoped separately from database equation orientation. Source location `JSON /primaryAccession; /organism/taxonId; /comments/2` MetaCyc:CPLX-9178 Source assertion: The native assembled protein lists its enzymatic-reaction association and described catalytic transformation. Source location `XML /ptools-xml/Protein/catalyzes; /ptools-xml/Protein/comment` PMID:20047909 Source assertion: Recombinant Mcl1 catalyzes beta-methylmalyl-CoA cleavage to glyoxylate and propionyl-CoA and the condensation of glyoxylate with acetyl-CoA to malyl-CoA. Source location `HTML section#sec17/p[2]; section#sec17/p[3]; section#sec17/p[4]`
L-malyl-CoA/β-methylmalyl-CoA lyase `MetaCyc:CPLX-9178`	catalyzes Catalysis by the assembled enzyme. Exact sequence bridges and source-specific evidence tiers are retained in the research ledger.	glyoxylate + acetyl-CoA => (S)-malyl-CoA `RHEA:16631`	UniProtKB:Q3J5L6 Source assertion: The selected gene product is assigned this catalytic reaction with ECO:0000269 evidence; directional physiological use is scoped separately from database equation orientation. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1` MetaCyc:CPLX-9178 Source assertion: The native assembled protein lists its enzymatic-reaction association and described catalytic transformation. Source location `XML /ptools-xml/Protein/catalyzes; /ptools-xml/Protein/comment` PMID:20047909 Source assertion: Recombinant Mcl1 catalyzes beta-methylmalyl-CoA cleavage to glyoxylate and propionyl-CoA and the condensation of glyoxylate with acetyl-CoA to malyl-CoA. Source location `HTML section#sec17/p[2]; section#sec17/p[3]; section#sec17/p[4]`
Ethylmalonyl-CoA/methylmalonyl-CoA epimerase `UniProtKB:Q3IZP4`	catalyzes One promiscuous epimerase supports the ethylmalonyl-CoA epimerization.	(2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA `RHEA:59730`	UniProtKB:Q3IZP4 Source assertion: The reviewed entry assigns this reaction with ECO:0000269 evidence; its deposited primary sequence matches the current selected sequence. The cited 2008 mutase paper is available here only as an abstract when applicable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1`
Ethylmalonyl-CoA/methylmalonyl-CoA epimerase `UniProtKB:Q3IZP4`	catalyzes The same epimerase supports the methylmalonyl-CoA branch.	(S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA `RHEA:20555`	UniProtKB:Q3IZP4 Source assertion: The reviewed entry assigns this reaction with ECO:0000269 evidence; its deposited primary sequence matches the current selected sequence. The cited 2008 mutase paper is available here only as an abstract when applicable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/2`
Mesaconyl-CoA hydratase `UniProtKB:Q3IZ78`	catalyzes Mesaconyl-C1-CoA hydration in this pathway; the reverse dehydration is used in the distinct Chloroflexus pathway. Recombinant enzyme was an approximately 80-kDa homodimer.	2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA `RHEA:38265`	UniProtKB:Q3IZ78 Source assertion: The reviewed entry assigns this reaction with ECO:0000269 evidence; its deposited primary sequence matches the current selected sequence. The cited 2008 mutase paper is available here only as an abstract when applicable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1` PMID:18065535 Source assertion: Recombinant R. sphaeroides mesaconyl-CoA hydratase converts beta-methylmalyl-CoA and mesaconyl-CoA reversibly; NMR locates the CoA thioester at mesaconate C1, and its EMC role is hydration. Source location `HTML section#sec24; section#sec35; section#sec36; section#sec40`
(3S)-malyl-CoA thioesterase `UniProtKB:D3JV05`	catalyzes Mcl2 hydrolyzes malyl-CoA without ATP formation. It is not Mcl1, not a beta-methylmalyl-CoA hydrolase, and not reversed malate-CoA ligase. Gel filtration leaves dimer versus trimer unresolved.	(S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) `RHEA:38292`	UniProtKB:D3JV05 Source assertion: The reviewed entry assigns this reaction with ECO:0000269 evidence; its deposited primary sequence matches the current selected sequence. The cited 2008 mutase paper is available here only as an abstract when applicable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1` PMID:20047909 Source assertion: Purified His-tagged Mcl2 hydrolyzes malyl-CoA to malate and CoA, but does not cleave malyl-CoA or beta-methylmalyl-CoA; 80-kDa gel filtration supports an unresolved dimer or trimer. Source location `HTML section#sec19/p[1]`
Methylmalonyl-CoA mutase `UniProtKB:Q3J4D7`	catalyzes Methylmalonyl-CoA mutase closes the propionyl branch at succinyl-CoA. Its homodimer annotation is by similarity, not a measured assembly in this strain.	(R)-methylmalonyl-CoA => succinyl-CoA `RHEA:22889`	UniProtKB:Q3J4D7 Source assertion: The reviewed entry assigns this reaction with ECO:0000269 evidence; its deposited primary sequence matches the current selected sequence. The cited 2008 mutase paper is available here only as an abstract when applicable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1`
Acetyl-CoA C-acetyltransferase `UniProtKB:Q3IZW1`	enables Candidate thiolase assignment is automatic and does not demonstrate that this is the sole strain thiolase used by the pathway.	2 acetyl-CoA => acetoacetyl-CoA + CoA `RHEA:21037`	UniProtKB:Q3IZW1 Source assertion: The unreviewed protein is assigned acetyl-CoA C-acetyltransferase activity, RHEA:21036, with ECO:0000256 PROSITE-ProRule PRU10020 evidence. Source location `JSON /primaryAccession; /organism/taxonId; /comments/0`
propionyl-CoA carboxylase `UniProtKB:Q3J4D9`	enables Subunit contribution to the combined propionyl-CoA carboxylase reaction; this edge does not assert that the isolated chain performs the entire reaction. No measured six-alpha/six-beta assembly is claimed.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	UniProtKB:Q3J4D9 Source assertion: Alpha-chain catalytic assignment is automatic ECO:0000256 ARBA00049495; KEGG requires K01965 together with K01966. Source location `JSON /primaryAccession; /organism/taxonId; /comments/0` KEGG:M00373 Source assertion: K01965+K01966 is a joint mandatory module requirement for propionyl-CoA carboxylase. Source location `ENTRY M00373 / DEFINITION; ORTHOLOGY K01965 and K01966`
Propionyl-CoA carboxylase beta chain `UniProtKB:Q3J4E3`	enables Subunit contribution to the combined propionyl-CoA carboxylase reaction; this edge does not assert that the isolated chain performs the entire reaction. No measured six-alpha/six-beta assembly is claimed.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	UniProtKB:Q3J4E3 Source assertion: The beta-chain entry assigns propionyl-CoA carboxylase activity with ECO:0000269 PMID26170412; that paper measures cellular enzyme activity and pccB expression, not purified-chain overall catalysis. Source location `JSON /primaryAccession; /organism/taxonId; /comments/0` KEGG:M00373 Source assertion: K01965+K01966 is a joint mandatory module requirement for propionyl-CoA carboxylase. Source location `ENTRY M00373 / DEFINITION; ORTHOLOGY K01965 and K01966`
Ethylmalonyl-CoA mutase `UniProtKB:Q3IZ90`	has_cofactor Reviewed experimental annotation; original mutase full text unavailable.	cobamamide `CHEBI:18408`	UniProtKB:Q3IZ90 Source assertion: The cofactor statement names cobamamide (CHEBI:18408); evidence ECO:0000269. Reviewed experimental annotation; original mutase full text unavailable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/2`
Methylmalonyl-CoA mutase `UniProtKB:Q3J4D7`	has_cofactor Reviewed experimental annotation; original mutase full text unavailable.	cobamamide `CHEBI:18408`	UniProtKB:Q3J4D7 Source assertion: The cofactor statement names cobamamide (CHEBI:18408); evidence ECO:0000269. Reviewed experimental annotation; original mutase full text unavailable. Source location `JSON /primaryAccession; /organism/taxonId; /comments/2`
Ethylmalonyl-CoA/methylmalonyl-CoA epimerase `UniProtKB:Q3IZP4`	has_cofactor Alternative supporting ions, not simultaneous occupancy or a demonstrated physiological metal; Mg and Ni do not support activity in the cited assays.	cobalt(2+) `CHEBI:48828`	UniProtKB:Q3IZP4 Source assertion: The cofactor statement names cobalt(2+) (CHEBI:48828); evidence ECO:0000269. Alternative supporting ions, not simultaneous occupancy or a demonstrated physiological metal; Mg and Ni do not support activity in the cited assays. Source location `JSON /primaryAccession; /organism/taxonId; /comments/3`
Ethylmalonyl-CoA/methylmalonyl-CoA epimerase `UniProtKB:Q3IZP4`	has_cofactor Alternative supporting ions, not simultaneous occupancy or a demonstrated physiological metal; Mg and Ni do not support activity in the cited assays.	manganese(2+) `CHEBI:29035`	UniProtKB:Q3IZP4 Source assertion: The cofactor statement names manganese(2+) (CHEBI:29035); evidence ECO:0000269. Alternative supporting ions, not simultaneous occupancy or a demonstrated physiological metal; Mg and Ni do not support activity in the cited assays. Source location `JSON /primaryAccession; /organism/taxonId; /comments/3`
(2S)-methylsuccinyl-CoA dehydrogenase `UniProtKB:D3JV03`	has_cofactor Bound FAD, one per subunit in the reviewed source. This is distinct from the separate whole ETF electron-acceptor states.	FAD(3-) `CHEBI:57692`	UniProtKB:D3JV03 Source assertion: The cofactor statement names FAD(3-) (CHEBI:57692); evidence ECO:0000269. Bound FAD, one per subunit in the reviewed source. This is distinct from the separate whole ETF electron-acceptor states. Source location `JSON /primaryAccession; /organism/taxonId; /comments/2`
propionyl-CoA carboxylase `UniProtKB:Q3J4D9`	has_cofactor Automatic ARBA annotation of biotin-dependent alpha-chain function, not direct measurement in this strain.	biotinate `CHEBI:57586`	UniProtKB:Q3J4D9 Source assertion: The cofactor statement names biotinate (CHEBI:57586); evidence ECO:0000256. Automatic ARBA annotation of biotin-dependent alpha-chain function, not direct measurement in this strain. Source location `JSON /primaryAccession; /organism/taxonId; /comments/1`
L-malyl-CoA/beta-methylmalyl-CoA lyase `UniProtKB:Q3J5L6`	has_cofactor Alternative divalent-ion assay support; Mn performed best after EDTA pretreatment. Mg-containing crystals do not establish exclusive physiological Mg use.	magnesium(2+) `CHEBI:18420`	UniProtKB:Q3J5L6 Source assertion: The cofactor statement names magnesium(2+) (CHEBI:18420); evidence ECO:0000269. Alternative divalent-ion assay support; Mn performed best after EDTA pretreatment. Mg-containing crystals do not establish exclusive physiological Mg use. Source location `JSON /primaryAccession; /organism/taxonId; /comments/4` PMID:20047909 Source assertion: Divalent cations support activity after EDTA treatment; Mcl1 favors Mn whereas Mcl2 favors Mg under the reported assays. These assays do not determine exclusive physiological occupancy. Source location `HTML section#sec17/p[3]; section#sec19/p[1]; section#t1`
L-malyl-CoA/beta-methylmalyl-CoA lyase `UniProtKB:Q3J5L6`	has_cofactor Alternative divalent-ion assay support; Mn performed best after EDTA pretreatment. Mg-containing crystals do not establish exclusive physiological Mg use.	manganese(2+) `CHEBI:29035`	UniProtKB:Q3J5L6 Source assertion: The cofactor statement names manganese(2+) (CHEBI:29035); evidence ECO:0000269. Alternative divalent-ion assay support; Mn performed best after EDTA pretreatment. Mg-containing crystals do not establish exclusive physiological Mg use. Source location `JSON /primaryAccession; /organism/taxonId; /comments/4` PMID:20047909 Source assertion: Divalent cations support activity after EDTA treatment; Mcl1 favors Mn whereas Mcl2 favors Mg under the reported assays. These assays do not determine exclusive physiological occupancy. Source location `HTML section#sec17/p[3]; section#sec19/p[1]; section#t1`
(3S)-malyl-CoA thioesterase `UniProtKB:D3JV05`	has_cofactor Mg supported thioester hydrolysis best at 10 mM in the primary assay; not a measured in vivo metal assignment.	magnesium(2+) `CHEBI:18420`	UniProtKB:D3JV05 Source assertion: The cofactor statement names magnesium(2+) (CHEBI:18420); evidence ECO:0000269. Mg supported thioester hydrolysis best at 10 mM in the primary assay; not a measured in vivo metal assignment. Source location `JSON /primaryAccession; /organism/taxonId; /comments/2` PMID:20047909 Source assertion: Divalent cations support activity after EDTA treatment; Mcl1 favors Mn whereas Mcl2 favors Mg under the reported assays. These assays do not determine exclusive physiological occupancy. Source location `HTML section#sec17/p[3]; section#sec19/p[1]; section#t1`
(3S)-malyl-CoA thioesterase `UniProtKB:D3JV05`	has_cofactor Mn is an alternative divalent-ion assay activator; Mg at 10 mM served best. Do not infer simultaneous Mn/Mg occupancy.	manganese(2+) `CHEBI:29035`	PMID:20047909 Source assertion: Purified Mcl2 activity was supported by Mg or Mn; testing after EDTA pretreatment found Mg at 10 mM best. Source location `HTML section#sec19/p[1]; section#t1`
Propionyl-CoA carboxylase regulator `UniProtKB:Q3J4E6`	regulates Indirect transcriptional control of the PCC step through pccB expression. Direct DNA binding was not established; propionyl-CoA as the PccR ligand was proposed rather than measured. The deletion retained acetate growth.	propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) `RHEA:23721`	PMID:26170412 Source assertion: Deleting pccR removed carbon-source-dependent pccB transcript and cellular PCC-activity regulation. Complementation restored propionate growth and cellular PCC activity; restored transcription was not measured. Soluble PccR purification failed, so direct promoter binding was not demonstrated. Source location `HTML section#sec3-3; section#T1; section#sec3-1; section#sec4/p[1]` UniProtKB:Q3J4E6 Source assertion: PccR controls propionyl-CoA assimilation through regulation of pccB expression, with ECO:0000269 PMID26170412 evidence. Source location `JSON /primaryAccession; /organism/taxonId; /comments/0`

References

KEGG:M00373 Ethylmalonyl pathway (source version: Complete module flatfile retrieved 2026-10-11; no release number supplied)
UniProtKB:Q3IZW1 Acetyl-CoA C-acetyltransferase (source version: UniProt entry 120, sequence 2, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3IZ91 Crotonyl-CoA carboxylase/reductase (source version: UniProt entry 109, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3IZP4 Ethylmalonyl-CoA/methylmalonyl-CoA epimerase (source version: UniProt entry 93, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3IZ90 Ethylmalonyl-CoA mutase (source version: UniProt entry 101, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:D3JV03 (2S)-methylsuccinyl-CoA dehydrogenase (source version: UniProt entry 51, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3IZ78 Mesaconyl-CoA hydratase (source version: UniProt entry 89, sequence 1, annotation 2026-06-10; original retrieved 2026-10-11)
UniProtKB:Q3J5L6 L-malyl-CoA/beta-methylmalyl-CoA lyase (source version: UniProt entry 111, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:D3JV05 (3S)-malyl-CoA thioesterase (source version: UniProt entry 78, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3J4D9 propionyl-CoA carboxylase (source version: UniProt entry 125, sequence 2, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3J4E3 Propionyl-CoA carboxylase beta chain (source version: UniProt entry 92, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3J4D7 Methylmalonyl-CoA mutase (source version: UniProt entry 104, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
UniProtKB:Q3J4E6 Propionyl-CoA carboxylase regulator (source version: UniProt entry 101, sequence 1, annotation 2026-09-02; original retrieved 2026-10-11)
MetaCyc:CPLX-7544 crotonyl-CoA carboxylase/reductase (source version: MetaCyc PGDB META 27.0; complete XML retrieved 2026-10-11)
MetaCyc:CPLX-8971 (2S)-methylsuccinyl-CoA dehydrogenase (source version: MetaCyc PGDB META 27.0; complete XML retrieved 2026-10-11)
MetaCyc:CPLX-8972 (2R)-ethylmalonyl-CoA mutase (source version: MetaCyc PGDB META 27.0; complete XML retrieved 2026-10-11)
MetaCyc:CPLX-9178 L-malyl-CoA/β-methylmalyl-CoA lyase (source version: MetaCyc PGDB META 27.0; complete XML retrieved 2026-10-11)
PMID:20957036 Methanol Assimilation in Methylobacterium extorquens AM1: Demonstration of All Enzymes and Their Regulation (source version: Complete original acquired; Full article body, methods, Table 1, figure captions and bibliography; not every figure visually inspected. Retrieved 2026-10-11.)
PMID:20047909 The Apparent Malate Synthase Activity of Rhodobacter sphaeroides Is Due to Two Paralogous Enzymes, (3S)-Malyl-Coenzyme A (CoA)/β-Methylmalyl-CoA Lyase and (3S)- Malyl-CoA Thioesterase (source version: Complete original acquired; Complete article body, methods, tables and figure captions; Figures 1 and 5 visually inspected; bibliography not systematically inspected. Retrieved 2026-10-11.)
PMID:19261854 Demonstration of the ethylmalonyl-CoA pathway by using 13C metabolomics (source version: Complete original acquired; Complete article body, methods, tables and figure captions; Figure 1 visually inspected; references not systematically inspected. Retrieved 2026-10-11.)
PMID:22105076 The Ethylmalonyl-CoA Pathway Is Used in Place of the Glyoxylate Cycle by Methylobacterium extorquens AM1 during Growth on Acetate (source version: Complete original acquired; Complete article body, methods, tables and captions; Figure 3 visually inspected; not all figures visually inspected. Retrieved 2026-10-11.)
PMID:17548827 Synthesis of C5-dicarboxylic acids from C2-units involving crotonyl-CoA carboxylase/reductase: The ethylmalonyl-CoA pathway (source version: Complete original acquired; Complete main article body, methods and captions; supplementary files/diagrams not inspected. Retrieved 2026-10-11.)
PMID:18065535 Mesaconyl-Coenzyme A Hydratase, a New Enzyme of Two Central Carbon Metabolic Pathways in Bacteria (source version: Complete original acquired; Complete main article body, methods, Table 1 and captions; diagrams not visually inspected. Retrieved 2026-10-11.)
PMID:29283425 Molecular Basis for Converting (2S)-Methylsuccinyl-CoA Dehydrogenase into an Oxidase (source version: Complete original acquired; Relevant Introduction, Results 2.1–2.3, Methods 4.1/4.2/4.4 and Table 1 inspected; not complete article/supplement visual inspection. Retrieved 2026-10-11.)
PMID:19703103 (2S)-Methylsuccinyl-CoA dehydrogenase closes the ethylmalonyl-CoA pathway for acetyl-CoA assimilation. (source version: Abstract metadata only; Primary abstract only via Europe PMC core metadata; Wiley PDF failed. Retrieved 2026-10-11.)
PMID:18819910 Ethylmalonyl-CoA mutase from Rhodobacter sphaeroides defines a new subclade of coenzyme B12-dependent acyl-CoA mutases. (source version: Abstract metadata only; Primary abstract only; DOI returned redirect shell, current JBC403, old host DNS failure; web tool failed. Retrieved 2026-10-11.)
PMID:26170412 Transcriptional Regulation by the Short-Chain Fatty Acyl Coenzyme A Regulator (ScfR) PccR Controls Propionyl Coenzyme A Assimilation by Rhodobacter sphaeroides (source version: Complete original retrieved 2026-10-11; Complete main body, methods, tables and captions inspected; supplements and figures not visually inspected)
PMID:24206647 The crystal structures of the tri-functional Chloroflexus aurantiacus and bi-functional Rhodobacter sphaeroides malyl-CoA lyases and comparison with CitE-like superfamily enzymes and malate synthases (source version: Complete original retrieved 2026-10-11; Selected Results sec7/sec9/sec10 and Methods sec18/sec19/sec20 inspected; not whole-paper or figure inspection)
PMID:19458256 Carboxylation mechanism and stereochemistry of crotonyl-CoA carboxylase/reductase, a carboxylating enoyl-thioester reductase (source version: Complete original retrieved 2026-10-11; Abstract, introduction, Table1, Results sec2–sec7 and Discussion opening inspected; not whole-paper or supplement inspection)
NCBIProtein:ADC44452.1 (2S)-methylsuccinyl-CoA dehydrogenase, original 548-aa protein (source version: Versioned NCBI GenBank protein XML retrieved 2026-10-11)
RHEA:21037 2 acetyl-CoA => acetoacetyl-CoA + CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:45798 acetoacetyl-CoA + NADPH + H(+) => (3R)-3-hydroxybutanoyl-CoA + NADP(+) (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:17850 (3R)-3-hydroxybutanoyl-CoA => (2E)-butenoyl-CoA + H2O (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:28084 (2E)-butenoyl-CoA + CO2 + NADPH => (2S)-ethylmalonyl-CoA + NADP(+) (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:59730 (2S)-ethylmalonyl-CoA => (2R)-ethylmalonyl-CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:45577 (2R)-ethylmalonyl-CoA => (2S)-methylsuccinyl-CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:45029 (2S)-methylsuccinyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) => 2-methylfumaryl-CoA + reduced [electron-transfer flavoprotein] (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:38265 2-methylfumaryl-CoA + H2O => (2R,3S)-beta-methylmalyl-CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:38260 (2R,3S)-beta-methylmalyl-CoA => propanoyl-CoA + glyoxylate (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:16631 glyoxylate + acetyl-CoA => (S)-malyl-CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:38292 (S)-malyl-CoA + H2O => (S)-malate + CoA + H(+) (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:23721 propanoyl-CoA + hydrogencarbonate + ATP => (S)-methylmalonyl-CoA + ADP + phosphate + H(+) (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:20555 (S)-methylmalonyl-CoA => (R)-methylmalonyl-CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)
RHEA:22889 (R)-methylmalonyl-CoA => succinyl-CoA (source version: Rhea release 142, 2026-09-02; complete original gzip RDF retrieved 2026-10-10)

Curation history

2026-10-11T21:18:20Z codex
- CREATE — Add the complete ethylmalonyl-CoA pathway with scoped microbial evidence
  Added complete KEGG:M00373 with all14 reactions,50 participants,105 edges,155 evidence items and44 references. The exact target SHA256 is1c58f2d1b27fd7a8a3928971a49311a742e004a1b28f349b9331b8fe0f369912. Original whole-record review and independent successor verify eight evidence wording/locator changes and all14 native directions; original findings remain archived. Canonical builders add17 source inputs/terms and13 ontology terms with every prior authority entry and metadata object preserved. Native MetaCyc PWY5741 ATP-forming termination remains distinct; exact PhaB/crotonase proteins, sequence differences, inferred assemblies, assay metals, ETF microscopic stoichiometry and abstract-only sources retain their limits. Duplicate searches included ignored/hidden files and followed symlinks. The dossier research/pathway_additions/2026-10-11-next-221 preserves separate original/correction/reassessment and authority receipts. Maintained rendering,full corpus gates,graph/KGX preservation and canonical review follow this adoption and are not claimed complete by this event.
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