L-isoleucine biosynthesis I (from threonine)

MetaCyc:ILEUSYN-PWY

L-isoleucine biosynthesis I converts L-threonine to 2-oxobutanoate, condenses 2-oxobutanoate with pyruvate to form (S)-2-ethyl-2-hydroxy-3-oxobutanoate, reduces and rearranges that intermediate to (2R,3R)-2,3-dihydroxy-3-methylpentanoate, dehydrates it to (S)-3-methyl-2-oxopentanoate, and transaminates that 2-oxo acid to L-isoleucine.

Pathway type

amino acid biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

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Pathway network

42 nodes · 57 asserted directed edges

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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
threonine ammonia-lyase `EC:4.3.1.19`	molecular activity
acetolactate synthase `EC:2.2.1.6`	molecular activity
ketol-acid reductoisomerase (NADP(+)) `EC:1.1.1.86`	molecular activity
dihydroxy-acid dehydratase `EC:4.2.1.9`	molecular activity
branched-chain-amino-acid transaminase `EC:2.6.1.42`	molecular activity
L-threonine `CHEBI:57926`	small molecule
2-oxobutanoate `CHEBI:16763`	small molecule
NH4(+) `CHEBI:28938`	small molecule
pyruvate `CHEBI:15361`	small molecule
H+ `CHEBI:15378`	small molecule
(S)-2-ethyl-2-hydroxy-3-oxobutanoate `CHEBI:49256`	small molecule
CO2 `CHEBI:16526`	small molecule
NADPH `CHEBI:57783`	small molecule
(2R,3R)-2,3-dihydroxy-3-methylpentanoate `CHEBI:49258`	small molecule
NADP(+) `CHEBI:58349`	small molecule
(S)-3-methyl-2-oxopentanoate `CHEBI:35146`	small molecule
H2O `CHEBI:15377`	small molecule
L-glutamate `CHEBI:29985`	small molecule
L-isoleucine `CHEBI:58045`	small molecule
2-oxoglutarate `CHEBI:16810`	small molecule
2-aminobut-2-enoic acid zwitterion `CHEBI:48306`	small molecule
2-iminobutanoic acid zwitterion `CHEBI:76545`	small molecule
Acetolactate synthase isozyme 3 large subunit `UniProtKB:P00893`	protein
L-valine zwitterion `CHEBI:57762`	small molecule
magnesium(2+) `CHEBI:18420`	cofactor
thiamine(1+) diphosphate(3-) `CHEBI:58937`	cofactor
L-threonine dehydratase biosynthetic IlvA `UniProtKB:P04968`	protein
pyridoxal 5'-phosphate(2-) `CHEBI:597326`	cofactor
Dihydroxy-acid dehydratase `UniProtKB:P05791`	protein
iron-sulfur cluster `CHEBI:30408`	cofactor
Ketol-acid reductoisomerase (NADP(+)) `UniProtKB:P05793`	protein
cytoplasm `GO:0005737`	cellular component
Branched-chain-amino-acid aminotransferase `UniProtKB:P0AB80`	protein
2-iminobutanoate/2-iminopropanoate deaminase `UniProtKB:P0AF93`	protein
L-threonine dehydratase catabolic TdcB `UniProtKB:P0AGF6`	protein
acetohydroxybutanoate synthase reaction `RHEA:27655`	reaction	left to right
acetohydroxy acid isomeroreductase reaction `RHEA:13495`	reaction	right to left
dihydroxy-acid dehydratase reaction `RHEA:27695`	reaction	left to right
L-isoleucine aminotransferase reaction `RHEA:24803`	reaction	right to left
L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	reaction	left to right
2-aminobut-2-enoate => 2-iminobutanoate `RHEA:39968`	reaction	left to right
2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
pyruvate `CHEBI:15361`	consumes	acetohydroxybutanoate synthase reaction `RHEA:27655`	RHEA:27655 Source assertion: Rhea lists CHEBI:15361 on the substrates side of RHEA:27655 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27655']/rh:substrates; rh:contains/rh:compound/rh:accession`
H+ `CHEBI:15378`	consumes	acetohydroxybutanoate synthase reaction `RHEA:27655`	RHEA:27655 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:27655 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27655']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-oxobutanoate `CHEBI:16763`	consumes	acetohydroxybutanoate synthase reaction `RHEA:27655`	RHEA:27655 Source assertion: Rhea lists CHEBI:16763 on the substrates side of RHEA:27655 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27655']/rh:substrates; rh:contains/rh:compound/rh:accession`
acetohydroxybutanoate synthase reaction `RHEA:27655`	produces	CO2 `CHEBI:16526`	RHEA:27655 Source assertion: Rhea lists CHEBI:16526 on the products side of RHEA:27655 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27655']/rh:products; rh:contains/rh:compound/rh:accession`
acetohydroxybutanoate synthase reaction `RHEA:27655`	produces	(S)-2-ethyl-2-hydroxy-3-oxobutanoate `CHEBI:49256`	RHEA:27655 Source assertion: Rhea lists CHEBI:49256 on the products side of RHEA:27655 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27655']/rh:products; rh:contains/rh:compound/rh:accession`
H+ `CHEBI:15378`	consumes	acetohydroxy acid isomeroreductase reaction `RHEA:13495`	RHEA:13495 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:13495 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13495']/rh:substrates; rh:contains/rh:compound/rh:accession`
(S)-2-ethyl-2-hydroxy-3-oxobutanoate `CHEBI:49256`	consumes	acetohydroxy acid isomeroreductase reaction `RHEA:13495`	RHEA:13495 Source assertion: Rhea lists CHEBI:49256 on the substrates side of RHEA:13495 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13495']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH `CHEBI:57783`	consumes	acetohydroxy acid isomeroreductase reaction `RHEA:13495`	RHEA:13495 Source assertion: Rhea lists CHEBI:57783 on the substrates side of RHEA:13495 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13495']/rh:substrates; rh:contains/rh:compound/rh:accession`
acetohydroxy acid isomeroreductase reaction `RHEA:13495`	produces	(2R,3R)-2,3-dihydroxy-3-methylpentanoate `CHEBI:49258`	RHEA:13495 Source assertion: Rhea lists CHEBI:49258 on the products side of RHEA:13495 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13495']/rh:products; rh:contains/rh:compound/rh:accession`
acetohydroxy acid isomeroreductase reaction `RHEA:13495`	produces	NADP(+) `CHEBI:58349`	RHEA:13495 Source assertion: Rhea lists CHEBI:58349 on the products side of RHEA:13495 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13495']/rh:products; rh:contains/rh:compound/rh:accession`
(2R,3R)-2,3-dihydroxy-3-methylpentanoate `CHEBI:49258`	consumes	dihydroxy-acid dehydratase reaction `RHEA:27695`	RHEA:27695 Source assertion: Rhea lists CHEBI:49258 on the substrates side of RHEA:27695 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27695']/rh:substrates; rh:contains/rh:compound/rh:accession`
dihydroxy-acid dehydratase reaction `RHEA:27695`	produces	H2O `CHEBI:15377`	RHEA:27695 Source assertion: Rhea lists CHEBI:15377 on the products side of RHEA:27695 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27695']/rh:products; rh:contains/rh:compound/rh:accession`
dihydroxy-acid dehydratase reaction `RHEA:27695`	produces	(S)-3-methyl-2-oxopentanoate `CHEBI:35146`	RHEA:27695 Source assertion: Rhea lists CHEBI:35146 on the products side of RHEA:27695 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27695']/rh:products; rh:contains/rh:compound/rh:accession`
L-glutamate `CHEBI:29985`	consumes	L-isoleucine aminotransferase reaction `RHEA:24803`	RHEA:24803 Source assertion: Rhea lists CHEBI:29985 on the substrates side of RHEA:24803 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24803']/rh:substrates; rh:contains/rh:compound/rh:accession`
(S)-3-methyl-2-oxopentanoate `CHEBI:35146`	consumes	L-isoleucine aminotransferase reaction `RHEA:24803`	RHEA:24803 Source assertion: Rhea lists CHEBI:35146 on the substrates side of RHEA:24803 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24803']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-isoleucine aminotransferase reaction `RHEA:24803`	produces	2-oxoglutarate `CHEBI:16810`	RHEA:24803 Source assertion: Rhea lists CHEBI:16810 on the products side of RHEA:24803 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24803']/rh:products; rh:contains/rh:compound/rh:accession`
L-isoleucine aminotransferase reaction `RHEA:24803`	produces	L-isoleucine `CHEBI:58045`	RHEA:24803 Source assertion: Rhea lists CHEBI:58045 on the products side of RHEA:24803 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24803']/rh:products; rh:contains/rh:compound/rh:accession`
L-threonine `CHEBI:57926`	consumes	L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	RHEA:40676 Source assertion: Rhea lists CHEBI:57926 on the substrates side of RHEA:40676 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40676']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	produces	H2O `CHEBI:15377`	RHEA:40676 Source assertion: Rhea lists CHEBI:15377 on the products side of RHEA:40676 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40676']/rh:products; rh:contains/rh:compound/rh:accession`
L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	produces	2-aminobut-2-enoic acid zwitterion `CHEBI:48306`	RHEA:40676 Source assertion: Rhea lists CHEBI:48306 on the products side of RHEA:40676 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40676']/rh:products; rh:contains/rh:compound/rh:accession`
2-aminobut-2-enoic acid zwitterion `CHEBI:48306`	consumes	2-aminobut-2-enoate => 2-iminobutanoate `RHEA:39968`	RHEA:39968 Source assertion: Rhea lists CHEBI:48306 on the substrates side of RHEA:39968 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/39968']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-aminobut-2-enoate => 2-iminobutanoate `RHEA:39968`	produces	2-iminobutanoic acid zwitterion `CHEBI:76545`	RHEA:39968 Source assertion: Rhea lists CHEBI:76545 on the products side of RHEA:39968 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/39968']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	RHEA:39976 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:39976 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/39976']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-iminobutanoic acid zwitterion `CHEBI:76545`	consumes	2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	RHEA:39976 Source assertion: Rhea lists CHEBI:76545 on the substrates side of RHEA:39976 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/39976']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	produces	2-oxobutanoate `CHEBI:16763`	RHEA:39976 Source assertion: Rhea lists CHEBI:16763 on the products side of RHEA:39976 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/39976']/rh:products; rh:contains/rh:compound/rh:accession`
2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	produces	NH4(+) `CHEBI:28938`	RHEA:39976 Source assertion: Rhea lists CHEBI:28938 on the products side of RHEA:39976 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/39976']/rh:products; rh:contains/rh:compound/rh:accession`
threonine ammonia-lyase `EC:4.3.1.19`	catalyzes	L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	MetaCyc:ILEUSYN-PWY Source assertion: The native pathway assigns EC:4.3.1.19 activity to the enzymatic step represented by RHEA:40676; 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:4573981 Threonine deaminase from Escherichia coli. I. Purification and properties. Source location `PubMed ArticleTitle`
acetolactate synthase `EC:2.2.1.6`	catalyzes	acetohydroxybutanoate synthase reaction `RHEA:27655`	RHEA:27654 Source assertion: Rhea associates EC:2.2.1.6 with the reaction family containing RHEA:27655. Source location `rh:ec` PMID:2675968 Kinetics and mechanism of acetohydroxy acid synthase isozyme III from Escherichia coli. Source location `PubMed ArticleTitle`
ketol-acid reductoisomerase (NADP(+)) `EC:1.1.1.86`	catalyzes	acetohydroxy acid isomeroreductase reaction `RHEA:13495`	RHEA:13493 Source assertion: Rhea associates EC:1.1.1.86 with the reaction family containing RHEA:13495. Source location `rh:ec` PMID:4562389 Isoleucine and valine metabolism in Escherichia coli. 18. Induction of acetohydroxy acid isomeroreductase Source location `PubMed ArticleTitle`
dihydroxy-acid dehydratase `EC:4.2.1.9`	catalyzes	dihydroxy-acid dehydratase reaction `RHEA:27695`	RHEA:27694 Source assertion: Rhea associates EC:4.2.1.9 with the reaction family containing RHEA:27695. Source location `rh:ec` PMID:13727223 Dihydroxy acid dehydrase: an enzyme involved in the biosynthesis of isoleucine and valine Source location `PubMed ArticleTitle`
branched-chain-amino-acid transaminase `EC:2.6.1.42`	catalyzes	L-isoleucine aminotransferase reaction `RHEA:24803`	RHEA:24801 Source assertion: Rhea associates EC:2.6.1.42 with the reaction family containing RHEA:24803. 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`
acetohydroxy acid isomeroreductase reaction `RHEA:13495`	precedes	dihydroxy-acid dehydratase reaction `RHEA:27695`	MetaCyc:ILEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:13495 before RHEA:27695 in this pathway. Shared intermediate: CHEBI:49258. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
acetohydroxybutanoate synthase reaction `RHEA:27655`	precedes	acetohydroxy acid isomeroreductase reaction `RHEA:13495`	MetaCyc:ILEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:27655 before RHEA:13495 in this pathway. Shared intermediate: CHEBI:49256. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
dihydroxy-acid dehydratase reaction `RHEA:27695`	precedes	L-isoleucine aminotransferase reaction `RHEA:24803`	MetaCyc:ILEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:27695 before RHEA:24803 in this pathway. Shared intermediate: CHEBI:35146. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
2-aminobut-2-enoate => 2-iminobutanoate `RHEA:39968`	precedes	2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	MetaCyc:ILEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:39968 before RHEA:39976 in this pathway. Shared intermediate: CHEBI:76545. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	precedes	acetohydroxybutanoate synthase reaction `RHEA:27655`	MetaCyc:ILEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:39976 before RHEA:27655 in this pathway. Shared intermediate: CHEBI:16763. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	precedes	2-aminobut-2-enoate => 2-iminobutanoate `RHEA:39968`	MetaCyc:ILEUSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:40676 before RHEA:39968 in this pathway. Shared intermediate: CHEBI:48306. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
Acetolactate synthase isozyme 3 large subunit `UniProtKB:P00893`	enables	acetohydroxybutanoate synthase reaction `RHEA:27655`	PMID:2675968 Source assertion: The study directly measures E. coli acetohydroxy acid synthase III producing acetohydroxybutyrate from pyruvate and 2-ketobutyrate; UniProt identifies its catalytic subunit as P00893. Source location `PubMed Abstract; AHAS isozyme III kinetics; UniProt proteinDescription and genes`
L-valine zwitterion `CHEBI:57762`	inhibits	Acetolactate synthase isozyme 3 large subunit `UniProtKB:P00893`	UniProtKB:P00893 Source assertion: UniProt activity-regulation annotation: Sensitive to valine inhibition Source location `comments[commentType='ACTIVITY REGULATION'].texts`
Acetolactate synthase isozyme 3 large subunit `UniProtKB:P00893`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P00893 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P00893 (evidence: ECO:0000250). Binds 1 Mg(2+) ion per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Acetolactate synthase isozyme 3 large subunit `UniProtKB:P00893`	has_cofactor	thiamine(1+) diphosphate(3-) `CHEBI:58937`	UniProtKB:P00893 Source assertion: UniProt lists CHEBI:58937 as a cofactor of UniProtKB:P00893 (evidence: ECO:0000250). Binds 1 thiamine pyrophosphate per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
L-threonine dehydratase biosynthetic IlvA `UniProtKB:P04968`	enables	L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	UniProtKB:P04968 Source assertion: UniProt annotates UniProtKB:P04968 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:40676. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
L-isoleucine `CHEBI:58045`	inhibits	L-threonine dehydratase biosynthetic IlvA `UniProtKB:P04968`	UniProtKB:P04968 Source assertion: UniProt activity-regulation annotation: Isoleucine allosterically inhibits whereas valine allosterically activates this enzyme Source location `comments[commentType='ACTIVITY REGULATION'].texts`
L-valine zwitterion `CHEBI:57762`	activates	L-threonine dehydratase biosynthetic IlvA `UniProtKB:P04968`	UniProtKB:P04968 Source assertion: UniProt activity-regulation annotation: Isoleucine allosterically inhibits whereas valine allosterically activates this enzyme Source location `comments[commentType='ACTIVITY REGULATION'].texts`
L-threonine dehydratase biosynthetic IlvA `UniProtKB:P04968`	has_cofactor	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P04968 Source assertion: UniProt lists CHEBI:597326 as a cofactor of UniProtKB:P04968 (evidence: ECO:0000269). Source location `comments[commentType='COFACTOR'].cofactors and note`
Dihydroxy-acid dehydratase `UniProtKB:P05791`	enables	dihydroxy-acid dehydratase reaction `RHEA:27695`	UniProtKB:P05791 Source assertion: UniProt annotates UniProtKB:P05791 with catalytic activity for the reaction family of RHEA:27695. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Dihydroxy-acid dehydratase `UniProtKB:P05791`	has_cofactor	iron-sulfur cluster `CHEBI:30408`	UniProtKB:P05791 Source assertion: UniProt lists CHEBI:30408 as a cofactor of UniProtKB:P05791 (evidence: ECO:0000255). Cluster nuclearity is left unspecified: the current UniProt annotation infers [2Fe-2S], while its caution cites older E. coli [4Fe-4S] evidence and a later M. tuberculosis result. Source location `comments[commentType='COFACTOR'].cofactors and note`
Dihydroxy-acid dehydratase `UniProtKB:P05791`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P05791 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P05791 (evidence: ECO:0000255). Source location `comments[commentType='COFACTOR'].cofactors and note`
Ketol-acid reductoisomerase (NADP(+)) `UniProtKB:P05793`	enables	acetohydroxy acid isomeroreductase reaction `RHEA:13495`	UniProtKB:P05793 Source assertion: UniProt annotates UniProtKB:P05793 with catalytic activity for the reaction family of RHEA:13495. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Ketol-acid reductoisomerase (NADP(+)) `UniProtKB:P05793`	located_in	cytoplasm `GO:0005737`	UniProtKB:P05793 Source assertion: UniProt locates UniProtKB:P05793 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
Ketol-acid reductoisomerase (NADP(+)) `UniProtKB:P05793`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P05793 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P05793 (evidence: ECO:0000255, ECO:0000269). Binds 2 magnesium ions per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Branched-chain-amino-acid aminotransferase `UniProtKB:P0AB80`	enables	L-isoleucine aminotransferase reaction `RHEA:24803`	UniProtKB:P0AB80 Source assertion: UniProt annotates UniProtKB:P0AB80 with catalytic activity for the reaction family of RHEA:24803. 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`
2-iminobutanoate/2-iminopropanoate deaminase `UniProtKB:P0AF93`	enables	2-iminobutanoate + H2O => 2-oxobutanoate + NH4(+) `RHEA:39976`	UniProtKB:P0AF93 Source assertion: UniProt annotates UniProtKB:P0AF93 with catalytic activity for the reaction family of RHEA:39976. Annotation evidence: ECO:0000250; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
2-iminobutanoate/2-iminopropanoate deaminase `UniProtKB:P0AF93`	located_in	cytoplasm `GO:0005737`	UniProtKB:P0AF93 Source assertion: UniProt locates UniProtKB:P0AF93 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
L-threonine dehydratase catabolic TdcB `UniProtKB:P0AGF6`	enables	L-threonine => 2-aminobut-2-enoate + H2O `RHEA:40676`	UniProtKB:P0AGF6 Source assertion: UniProt annotates UniProtKB:P0AGF6 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:40676. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
L-threonine dehydratase catabolic TdcB `UniProtKB:P0AGF6`	has_cofactor	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P0AGF6 Source assertion: UniProt lists CHEBI:597326 as a cofactor of UniProtKB:P0AGF6 (evidence: ECO:0000269). Source location `comments[commentType='COFACTOR'].cofactors and note`

References

MetaCyc:ILEUSYN-PWY MetaCyc L-isoleucine biosynthesis I (from threonine) pathway (source version: 22.5)
RHEA:22108 Rhea L-threonine ammonia-lyase reaction (source version: 139)
RHEA:22109 Rhea L-threonine-to-2-oxobutanoate direction (source version: 139)
RHEA:27654 Rhea acetohydroxybutanoate synthase reaction (source version: 139)
RHEA:27655 Rhea acetohydroxybutanoate synthase direction (source version: 139)
RHEA:13493 Rhea acetohydroxy acid isomeroreductase reaction (source version: 139)
RHEA:13495 Rhea biosynthetic acetohydroxy acid isomeroreductase direction (source version: 139)
RHEA:27694 Rhea dihydroxy-acid dehydratase reaction (source version: 139)
RHEA:27695 Rhea dihydroxy-acid-to-3-methyl-2-oxopentanoate direction (source version: 139)
RHEA:24801 Rhea branched-chain-amino-acid transaminase reaction (source version: 139)
RHEA:24803 Rhea biosynthetic L-isoleucine transaminase direction (source version: 139)
PMID:4573981 Calhoun et al., Journal of Biological Chemistry, 1973
PMID:2675968 Gollop et al., Biochemistry, 1989
PMID:4562389 Ratzkin et al., Journal of Bacteriology, 1972
PMID:13727223 Myers, Journal of Biological Chemistry, 1961
PMID:378964 Lee-Peng et al., Journal of Bacteriology, 1979
RHEA:40676 RHEA:40676 authority record (source version: 139)
RHEA:39968 RHEA:39968 authority record (source version: 139)
RHEA:39976 RHEA:39976 authority record (source version: 139)
UniProtKB:P00893 UniProtKB:P00893 authority record (source version: 2026_03)
UniProtKB:P04968 UniProtKB:P04968 authority record (source version: 2026_03)
UniProtKB:P05791 UniProtKB:P05791 authority record (source version: 2026_03)
UniProtKB:P05793 UniProtKB:P05793 authority record (source version: 2026_03)
UniProtKB:P0AB80 UniProtKB:P0AB80 authority record (source version: 2026_03)
UniProtKB:P0AF93 UniProtKB:P0AF93 authority record (source version: 2026_03)
UniProtKB:P0AGF6 UniProtKB:P0AGF6 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 5 to 7; 0 directed-ID corrections; 7 protein annotations, 8 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:22109. Cluster nuclearity is left unspecified: the current UniProt annotation infers [2Fe-2S], while its caution cites older E. coli [4Fe-4S] evidence and a later M. tuberculosis result.
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