L-leucine biosynthesis

MetaCyc:LEUSYN-PWY

L-leucine biosynthesis extends 3-methyl-2-oxobutanoate with acetyl-CoA to (2S)-2-isopropylmalate, isomerizes it to (2R,3S)-3-isopropylmalate, oxidatively decarboxylates that intermediate to 4-methyl-2-oxopentanoate, and transaminates it to L-leucine.

Pathway type

amino acid biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

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Pathway network

36 nodes · 49 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.

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Chemical / cofactor
Protein / complex
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Cell / process context
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli `NCBITaxon:562`	taxon
2-isopropylmalate synthase `EC:2.3.3.13`	molecular activity
3-isopropylmalate dehydratase `EC:4.2.1.33`	molecular activity
3-isopropylmalate dehydrogenase `EC:1.1.1.85`	molecular activity
branched-chain-amino-acid transaminase `EC:2.6.1.42`	molecular activity
3-methyl-2-oxobutanoate `CHEBI:11851`	small molecule
acetyl-CoA `CHEBI:57288`	small molecule
H2O `CHEBI:15377`	small molecule
(2S)-2-isopropylmalate `CHEBI:1178`	small molecule
CoA `CHEBI:57287`	small molecule
H+ `CHEBI:15378`	small molecule
(2R,3S)-3-isopropylmalate `CHEBI:35121`	small molecule
NAD(+) `CHEBI:57540`	small molecule
4-methyl-2-oxopentanoate `CHEBI:17865`	small molecule
CO2 `CHEBI:16526`	small molecule
NADH `CHEBI:57945`	small molecule
L-glutamate `CHEBI:29985`	small molecule
L-leucine `CHEBI:57427`	small molecule
2-oxoglutarate `CHEBI:16810`	small molecule
2-isopropylmaleate(2-) `CHEBI:58085`	small molecule
(2S)-2-isopropyl-3-oxosuccinate(2-) `CHEBI:17214`	small molecule
2-isopropylmalate synthase `UniProtKB:P09151`	protein
cytoplasm `GO:0005737`	cellular component
manganese(2+) `CHEBI:29035`	cofactor
3-isopropylmalate dehydratase large subunit `UniProtKB:P0A6A6`	protein
tetra-mu3-sulfido-tetrairon `CHEBI:49883`	cofactor
Branched-chain-amino-acid aminotransferase `UniProtKB:P0AB80`	protein
pyridoxal 5'-phosphate(2-) `CHEBI:597326`	cofactor
3-isopropylmalate dehydrogenase `UniProtKB:P30125`	protein
magnesium(2+) `CHEBI:18420`	cofactor
3-isopropylmalate dehydratase small subunit `UniProtKB:P30126`	protein
2-isopropylmalate synthase reaction `RHEA:21525`	reaction	left to right
L-leucine aminotransferase reaction `RHEA:18323`	reaction	right to left
(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	reaction	right to left
2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	reaction	right to left
(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	reaction	left to right
(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
3-methyl-2-oxobutanoate `CHEBI:11851`	consumes	2-isopropylmalate synthase reaction `RHEA:21525`	RHEA:21525 Source assertion: Rhea lists CHEBI:11851 on the substrates side of RHEA:21525 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21525']/rh:substrates; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	2-isopropylmalate synthase reaction `RHEA:21525`	RHEA:21525 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:21525 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21525']/rh:substrates; rh:contains/rh:compound/rh:accession`
acetyl-CoA `CHEBI:57288`	consumes	2-isopropylmalate synthase reaction `RHEA:21525`	RHEA:21525 Source assertion: Rhea lists CHEBI:57288 on the substrates side of RHEA:21525 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21525']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-isopropylmalate synthase reaction `RHEA:21525`	produces	(2S)-2-isopropylmalate `CHEBI:1178`	RHEA:21525 Source assertion: Rhea lists CHEBI:1178 on the products side of RHEA:21525 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21525']/rh:products; rh:contains/rh:compound/rh:accession`
2-isopropylmalate synthase reaction `RHEA:21525`	produces	H+ `CHEBI:15378`	RHEA:21525 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:21525 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21525']/rh:products; rh:contains/rh:compound/rh:accession`
2-isopropylmalate synthase reaction `RHEA:21525`	produces	CoA `CHEBI:57287`	RHEA:21525 Source assertion: Rhea lists CHEBI:57287 on the products side of RHEA:21525 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21525']/rh:products; rh:contains/rh:compound/rh:accession`
4-methyl-2-oxopentanoate `CHEBI:17865`	consumes	L-leucine aminotransferase reaction `RHEA:18323`	RHEA:18323 Source assertion: Rhea lists CHEBI:17865 on the substrates side of RHEA:18323 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18323']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-glutamate `CHEBI:29985`	consumes	L-leucine aminotransferase reaction `RHEA:18323`	RHEA:18323 Source assertion: Rhea lists CHEBI:29985 on the substrates side of RHEA:18323 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18323']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-leucine aminotransferase reaction `RHEA:18323`	produces	2-oxoglutarate `CHEBI:16810`	RHEA:18323 Source assertion: Rhea lists CHEBI:16810 on the products side of RHEA:18323 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18323']/rh:products; rh:contains/rh:compound/rh:accession`
L-leucine aminotransferase reaction `RHEA:18323`	produces	L-leucine `CHEBI:57427`	RHEA:18323 Source assertion: Rhea lists CHEBI:57427 on the products side of RHEA:18323 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18323']/rh:products; rh:contains/rh:compound/rh:accession`
(2S)-2-isopropylmalate `CHEBI:1178`	consumes	(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	RHEA:16295 Source assertion: Rhea lists CHEBI:1178 on the substrates side of RHEA:16295 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16295']/rh:substrates; rh:contains/rh:compound/rh:accession`
(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	produces	H2O `CHEBI:15377`	RHEA:16295 Source assertion: Rhea lists CHEBI:15377 on the products side of RHEA:16295 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16295']/rh:products; rh:contains/rh:compound/rh:accession`
(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	produces	2-isopropylmaleate(2-) `CHEBI:58085`	RHEA:16295 Source assertion: Rhea lists CHEBI:58085 on the products side of RHEA:16295 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16295']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	RHEA:10678 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:10678 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10678']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-isopropylmaleate(2-) `CHEBI:58085`	consumes	2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	RHEA:10678 Source assertion: Rhea lists CHEBI:58085 on the substrates side of RHEA:10678 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10678']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	produces	(2R,3S)-3-isopropylmalate `CHEBI:35121`	RHEA:10678 Source assertion: Rhea lists CHEBI:35121 on the products side of RHEA:10678 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10678']/rh:products; rh:contains/rh:compound/rh:accession`
(2R,3S)-3-isopropylmalate `CHEBI:35121`	consumes	(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	RHEA:10893 Source assertion: Rhea lists CHEBI:35121 on the substrates side of RHEA:10893 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10893']/rh:substrates; rh:contains/rh:compound/rh:accession`
NAD(+) `CHEBI:57540`	consumes	(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	RHEA:10893 Source assertion: Rhea lists CHEBI:57540 on the substrates side of RHEA:10893 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10893']/rh:substrates; rh:contains/rh:compound/rh:accession`
(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	produces	H+ `CHEBI:15378`	RHEA:10893 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:10893 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10893']/rh:products; rh:contains/rh:compound/rh:accession`
(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	produces	(2S)-2-isopropyl-3-oxosuccinate(2-) `CHEBI:17214`	RHEA:10893 Source assertion: Rhea lists CHEBI:17214 on the products side of RHEA:10893 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10893']/rh:products; rh:contains/rh:compound/rh:accession`
(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	produces	NADH `CHEBI:57945`	RHEA:10893 Source assertion: Rhea lists CHEBI:57945 on the products side of RHEA:10893 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10893']/rh:products; rh:contains/rh:compound/rh:accession`
H+ `CHEBI:15378`	consumes	(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	RHEA:25079 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:25079 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25079']/rh:substrates; rh:contains/rh:compound/rh:accession`
(2S)-2-isopropyl-3-oxosuccinate(2-) `CHEBI:17214`	consumes	(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	RHEA:25079 Source assertion: Rhea lists CHEBI:17214 on the substrates side of RHEA:25079 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25079']/rh:substrates; rh:contains/rh:compound/rh:accession`
(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	produces	CO2 `CHEBI:16526`	RHEA:25079 Source assertion: Rhea lists CHEBI:16526 on the products side of RHEA:25079 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25079']/rh:products; rh:contains/rh:compound/rh:accession`
(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	produces	4-methyl-2-oxopentanoate `CHEBI:17865`	RHEA:25079 Source assertion: Rhea lists CHEBI:17865 on the products side of RHEA:25079 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25079']/rh:products; rh:contains/rh:compound/rh:accession`
2-isopropylmalate synthase `EC:2.3.3.13`	catalyzes	2-isopropylmalate synthase reaction `RHEA:21525`	RHEA:21524 Source assertion: Rhea associates EC:2.3.3.13 with the reaction family containing RHEA:21525. Source location `rh:ec`
3-isopropylmalate dehydratase `EC:4.2.1.33`	catalyzes	(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	MetaCyc:LEUSYN-PWY Source assertion: The native pathway assigns EC:4.2.1.33 activity to the enzymatic step represented by RHEA:16295; this is a component step when the EC definition is an overall reaction. Source location `Pathway/reaction-layout; Reaction/enzymatic-reaction and component-reaction relationships` PMID:14087357 The biosynthesis of leucine. II. The enzymic isomerization of beta-carboxy-beta-hydroxyisocaproate and alpha-hydroxy-beta-carboxyisocaproate. Source location `PubMed ArticleTitle`
3-isopropylmalate dehydratase `EC:4.2.1.33`	catalyzes	2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	MetaCyc:LEUSYN-PWY Source assertion: The native pathway assigns EC:4.2.1.33 activity to the enzymatic step represented by RHEA:10678; this is a component step when the EC definition is an overall reaction. Source location `Pathway/reaction-layout; Reaction/enzymatic-reaction and component-reaction relationships` PMID:14087357 The biosynthesis of leucine. II. The enzymic isomerization of beta-carboxy-beta-hydroxyisocaproate and alpha-hydroxy-beta-carboxyisocaproate. Source location `PubMed ArticleTitle`
3-isopropylmalate dehydrogenase `EC:1.1.1.85`	catalyzes	(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	MetaCyc:LEUSYN-PWY Source assertion: The native pathway assigns EC:1.1.1.85 activity to the enzymatic step represented by RHEA:10893; this is a component step when the EC definition is an overall reaction. Source location `Pathway/reaction-layout; Reaction/enzymatic-reaction and component-reaction relationships` PMID:14087358 The biosynthesis of leucine. III. The conversion of alpha-hydroxy-beta-carboxyisocaproate to alpha-ketoisocaproate. Source location `PubMed ArticleTitle`
branched-chain-amino-acid transaminase `EC:2.6.1.42`	catalyzes	L-leucine aminotransferase reaction `RHEA:18323`	RHEA:18321 Source assertion: Rhea associates EC:2.6.1.42 with the reaction family containing RHEA:18323. Source location `rh:ec` PMID:378964 Transaminase B from Escherichia coli: quaternary structure, amino-terminal sequence, substrate specificity, and absence of a separate valine-alpha-ketoglutarate activity. Source location `PubMed ArticleTitle`
2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	precedes	(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	MetaCyc:LEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:10678 before RHEA:10893 in this pathway. Shared intermediate: CHEBI:35121. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	precedes	(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	MetaCyc:LEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:10893 before RHEA:25079 in this pathway. Shared intermediate: CHEBI:17214. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	precedes	2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	MetaCyc:LEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:16295 before RHEA:10678 in this pathway. Shared intermediate: CHEBI:58085. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
2-isopropylmalate synthase reaction `RHEA:21525`	precedes	(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	MetaCyc:LEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:21525 before RHEA:16295 in this pathway. Shared intermediate: CHEBI:1178. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
(2S)-2-isopropyl-3-oxosuccinate + H(+) => 4-methyl-2-oxopentanoate + CO2 `RHEA:25079`	precedes	L-leucine aminotransferase reaction `RHEA:18323`	MetaCyc:LEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:25079 before RHEA:18323 in this pathway. Shared intermediate: CHEBI:17865. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
2-isopropylmalate synthase `UniProtKB:P09151`	enables	2-isopropylmalate synthase reaction `RHEA:21525`	UniProtKB:P09151 Source assertion: UniProt annotates UniProtKB:P09151 with catalytic activity for the reaction family of RHEA:21525. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
2-isopropylmalate synthase `UniProtKB:P09151`	located_in	cytoplasm `GO:0005737`	UniProtKB:P09151 Source assertion: UniProt locates UniProtKB:P09151 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000255. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
2-isopropylmalate synthase `UniProtKB:P09151`	has_cofactor	manganese(2+) `CHEBI:29035`	UniProtKB:P09151 Source assertion: UniProt lists CHEBI:29035 as a cofactor of UniProtKB:P09151 (evidence: ECO:0000255). Source location `comments[commentType='COFACTOR'].cofactors and note`
3-isopropylmalate dehydratase large subunit `UniProtKB:P0A6A6`	enables	(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	UniProtKB:P0A6A6 Source assertion: UniProt annotates UniProtKB:P0A6A6 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:16295. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
3-isopropylmalate dehydratase large subunit `UniProtKB:P0A6A6`	enables	2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	UniProtKB:P0A6A6 Source assertion: UniProt annotates UniProtKB:P0A6A6 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:10678. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
3-isopropylmalate dehydratase large subunit `UniProtKB:P0A6A6`	has_cofactor	tetra-mu3-sulfido-tetrairon `CHEBI:49883`	UniProtKB:P0A6A6 Source assertion: UniProt lists CHEBI:49883 as a cofactor of UniProtKB:P0A6A6 (evidence: ECO:0000255). Binds 1 [4Fe-4S] cluster per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Branched-chain-amino-acid aminotransferase `UniProtKB:P0AB80`	enables	L-leucine aminotransferase reaction `RHEA:18323`	UniProtKB:P0AB80 Source assertion: UniProt annotates UniProtKB:P0AB80 with catalytic activity for the reaction family of RHEA:18323. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Branched-chain-amino-acid aminotransferase `UniProtKB:P0AB80`	has_cofactor	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P0AB80 Source assertion: UniProt lists CHEBI:597326 as a cofactor of UniProtKB:P0AB80 (evidence: curated annotation). Source location `comments[commentType='COFACTOR'].cofactors and note`
3-isopropylmalate dehydrogenase `UniProtKB:P30125`	enables	(2R,3S)-3-isopropylmalate + NAD(+) => (2S)-2-isopropyl-3-oxosuccinate + NADH + H(+) `RHEA:10893`	UniProtKB:P30125 Source assertion: UniProt annotates UniProtKB:P30125 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:10893. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
3-isopropylmalate dehydrogenase `UniProtKB:P30125`	located_in	cytoplasm `GO:0005737`	UniProtKB:P30125 Source assertion: UniProt locates UniProtKB:P30125 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000255. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
3-isopropylmalate dehydrogenase `UniProtKB:P30125`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P30125 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P30125 (evidence: ECO:0000255, ECO:0000269). Binds 1 Mg(2+) or Mn(2+) ion per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
3-isopropylmalate dehydrogenase `UniProtKB:P30125`	has_cofactor	manganese(2+) `CHEBI:29035`	UniProtKB:P30125 Source assertion: UniProt lists CHEBI:29035 as a cofactor of UniProtKB:P30125 (evidence: ECO:0000255, ECO:0000269). Binds 1 Mg(2+) or Mn(2+) ion per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
3-isopropylmalate dehydratase small subunit `UniProtKB:P30126`	enables	(2S)-2-isopropylmalate => 2-isopropylmaleate + H2O `RHEA:16295`	UniProtKB:P30126 Source assertion: UniProt annotates UniProtKB:P30126 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:16295. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
3-isopropylmalate dehydratase small subunit `UniProtKB:P30126`	enables	2-isopropylmaleate + H2O => (2R,3S)-3-isopropylmalate `RHEA:10678`	UniProtKB:P30126 Source assertion: UniProt annotates UniProtKB:P30126 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:10678. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`

References

MetaCyc:LEUSYN-PWY MetaCyc L-leucine biosynthesis pathway (source version: 22.5)
RHEA:21524 Rhea 2-isopropylmalate synthase reaction (source version: 139)
RHEA:21525 Rhea 2-isopropylmalate synthase direction (source version: 139)
RHEA:32287 Rhea 3-isopropylmalate dehydratase reaction (source version: 139)
RHEA:32289 Rhea biosynthetic 3-isopropylmalate dehydratase direction (source version: 139)
RHEA:32271 Rhea 3-isopropylmalate dehydrogenase reaction (source version: 139)
RHEA:32272 Rhea 4-methyl-2-oxopentanoate-forming direction (source version: 139)
RHEA:18321 Rhea L-leucine transaminase reaction (source version: 139)
RHEA:18323 Rhea biosynthetic L-leucine transaminase direction (source version: 139)
PMID:4976555 Kohlhaw et al., Journal of Biological Chemistry, 1969
PMID:14087357 Gross et al., Biochemistry, 1963
PMID:14087358 Burns et al., Biochemistry, 1963
PMID:378964 Lee-Peng et al., Journal of Bacteriology, 1979
RHEA:16295 RHEA:16295 authority record (source version: 139)
RHEA:10678 RHEA:10678 authority record (source version: 139)
RHEA:10893 RHEA:10893 authority record (source version: 139)
RHEA:25079 RHEA:25079 authority record (source version: 139)
UniProtKB:P09151 UniProtKB:P09151 authority record (source version: 2026_03)
UniProtKB:P0A6A6 UniProtKB:P0A6A6 authority record (source version: 2026_03)
UniProtKB:P0AB80 UniProtKB:P0AB80 authority record (source version: 2026_03)
UniProtKB:P30125 UniProtKB:P30125 authority record (source version: 2026_03)
UniProtKB:P30126 UniProtKB:P30126 authority record (source version: 2026_03)

Curation history

2026-10-05T06:25:52Z codex
- EDIT — Review causal chemistry and add sourced molecular context
  Reviewed the entire record against MetaCyc 22.5 native pathway XML (including nested pathways), Rhea 139 explicit sides and directions, ENZYME 02-Sep-2026, PubMed records, and reviewed UniProt 2026_03 annotations within the record's taxon scope. Replaced generated structured-source quotations with source_assertion and source_locator. Typed molecular activities and participants. Reaction count 4 to 6; 0 directed-ID corrections; 5 protein annotations, 5 cofactor annotations and 2 sourced locations. All Rhea reaction substrate/product sets checked against independent Rhea authority; native pathway leaf coverage and source exceptions recorded in reports/causal_graph_review/metacyc-review.json. Full source URLs, versions and byte hashes are in metacyc-sources.json. All 50 MetaCyc records passed native schema validation; six targeted chemistry/evidence regression tests passed. Missing protein or cofactor annotations are not treated as biological absence; qualifications and exclusions are preserved in the ledger. Expanded combined reaction steps: RHEA:32289, RHEA:32272. Removed Salmonella typhimurium article-title evidence from the E. coli enzyme edge; E. coli catalysis is supported separately by MetaCyc and UniProt.
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