L-methionine biosynthesis I

MetaCyc:HOMOSER-METSYN-PWY

L-methionine biosynthesis I activates L-homoserine as O-succinyl-L-homoserine, condenses it with L-cysteine to form L,L-cystathionine, hydrolyzes L,L-cystathionine to L-homocysteine, and methylates L-homocysteine to L-methionine through either cobalamin-dependent or cobalamin-independent methionine synthase.

Pathway type

amino acid biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

Read the source YAML

Pathway network

40 nodes · 50 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

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

Show at full size (scroll to explore)

Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli `NCBITaxon:562`	taxon
homoserine O-succinyltransferase `EC:2.3.1.46`	molecular activity
cystathionine gamma-synthase `EC:2.5.1.48`	molecular activity
cystathionine beta-lyase MetC `UniProtKB:P06721`	protein
methionine synthase `EC:2.1.1.13`	molecular activity
5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase `EC:2.1.1.14`	molecular activity
L-homoserine `CHEBI:57476`	small molecule
succinyl-CoA `CHEBI:57292`	small molecule
O-succinyl-L-homoserine `CHEBI:57661`	small molecule
CoA `CHEBI:57287`	small molecule
L-cysteine `CHEBI:35235`	small molecule
L,L-cystathionine `CHEBI:58161`	small molecule
succinate `CHEBI:30031`	small molecule
H+ `CHEBI:15378`	small molecule
H2O `CHEBI:15377`	small molecule
L-homocysteine `CHEBI:58199`	small molecule
pyruvate `CHEBI:15361`	small molecule
NH4(+) `CHEBI:28938`	small molecule
(6S)-5-methyl-5,6,7,8-tetrahydrofolate `CHEBI:18608`	small molecule
(6S)-5,6,7,8-tetrahydrofolate `CHEBI:57453`	small molecule
5-methyltetrahydropteroyltri-L-glutamate `CHEBI:58207`	small molecule
tetrahydropteroyltri-L-glutamate `CHEBI:58140`	small molecule
L-methionine `CHEBI:57844`	small molecule
2-ammonioprop-2-enoate `CHEBI:76565`	small molecule
2-iminiopropionate `CHEBI:44400`	small molecule
Cystathionine gamma-synthase `UniProtKB:P00935`	protein
cytoplasm `GO:0005737`	cellular component
pyridoxal 5'-phosphate(2-) `CHEBI:597326`	cofactor
Homoserine O-succinyltransferase `UniProtKB:P07623`	protein
2-iminobutanoate/2-iminopropanoate deaminase `UniProtKB:P0AF93`	protein
Methionine synthase `UniProtKB:P13009`	protein
methylcobalamin `CHEBI:28115`	cofactor
zinc(2+) `CHEBI:29105`	cofactor
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase `UniProtKB:P25665`	protein
homoserine O-succinyltransferase reaction `RHEA:22009`	reaction	left to right
cystathionine gamma-synthase reaction `RHEA:20398`	reaction	left to right
cobalamin-dependent methionine synthase reaction `RHEA:11173`	reaction	left to right
cobalamin-independent methionine synthase reaction `RHEA:21197`	reaction	left to right
L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	reaction	left to right
2-aminoprop-2-enoate => 2-iminopropanoate `RHEA:40668`	reaction	left to right
2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
succinyl-CoA `CHEBI:57292`	consumes	homoserine O-succinyltransferase reaction `RHEA:22009`	RHEA:22009 Source assertion: Rhea lists CHEBI:57292 on the substrates side of RHEA:22009 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22009']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-homoserine `CHEBI:57476`	consumes	homoserine O-succinyltransferase reaction `RHEA:22009`	RHEA:22009 Source assertion: Rhea lists CHEBI:57476 on the substrates side of RHEA:22009 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22009']/rh:substrates; rh:contains/rh:compound/rh:accession`
homoserine O-succinyltransferase reaction `RHEA:22009`	produces	CoA `CHEBI:57287`	RHEA:22009 Source assertion: Rhea lists CHEBI:57287 on the products side of RHEA:22009 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22009']/rh:products; rh:contains/rh:compound/rh:accession`
homoserine O-succinyltransferase reaction `RHEA:22009`	produces	O-succinyl-L-homoserine `CHEBI:57661`	RHEA:22009 Source assertion: Rhea lists CHEBI:57661 on the products side of RHEA:22009 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22009']/rh:products; rh:contains/rh:compound/rh:accession`
L-cysteine `CHEBI:35235`	consumes	cystathionine gamma-synthase reaction `RHEA:20398`	RHEA:20398 Source assertion: Rhea lists CHEBI:35235 on the substrates side of RHEA:20398 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20398']/rh:substrates; rh:contains/rh:compound/rh:accession`
O-succinyl-L-homoserine `CHEBI:57661`	consumes	cystathionine gamma-synthase reaction `RHEA:20398`	RHEA:20398 Source assertion: Rhea lists CHEBI:57661 on the substrates side of RHEA:20398 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20398']/rh:substrates; rh:contains/rh:compound/rh:accession`
cystathionine gamma-synthase reaction `RHEA:20398`	produces	H+ `CHEBI:15378`	RHEA:20398 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:20398 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20398']/rh:products; rh:contains/rh:compound/rh:accession`
cystathionine gamma-synthase reaction `RHEA:20398`	produces	succinate `CHEBI:30031`	RHEA:20398 Source assertion: Rhea lists CHEBI:30031 on the products side of RHEA:20398 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20398']/rh:products; rh:contains/rh:compound/rh:accession`
cystathionine gamma-synthase reaction `RHEA:20398`	produces	L,L-cystathionine `CHEBI:58161`	RHEA:20398 Source assertion: Rhea lists CHEBI:58161 on the products side of RHEA:20398 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20398']/rh:products; rh:contains/rh:compound/rh:accession`
(6S)-5-methyl-5,6,7,8-tetrahydrofolate `CHEBI:18608`	consumes	cobalamin-dependent methionine synthase reaction `RHEA:11173`	RHEA:11173 Source assertion: Rhea lists CHEBI:18608 on the substrates side of RHEA:11173 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11173']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-homocysteine `CHEBI:58199`	consumes	cobalamin-dependent methionine synthase reaction `RHEA:11173`	RHEA:11173 Source assertion: Rhea lists CHEBI:58199 on the substrates side of RHEA:11173 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11173']/rh:substrates; rh:contains/rh:compound/rh:accession`
cobalamin-dependent methionine synthase reaction `RHEA:11173`	produces	(6S)-5,6,7,8-tetrahydrofolate `CHEBI:57453`	RHEA:11173 Source assertion: Rhea lists CHEBI:57453 on the products side of RHEA:11173 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11173']/rh:products; rh:contains/rh:compound/rh:accession`
cobalamin-dependent methionine synthase reaction `RHEA:11173`	produces	L-methionine `CHEBI:57844`	RHEA:11173 Source assertion: Rhea lists CHEBI:57844 on the products side of RHEA:11173 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11173']/rh:products; rh:contains/rh:compound/rh:accession`
L-homocysteine `CHEBI:58199`	consumes	cobalamin-independent methionine synthase reaction `RHEA:21197`	RHEA:21197 Source assertion: Rhea lists CHEBI:58199 on the substrates side of RHEA:21197 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21197']/rh:substrates; rh:contains/rh:compound/rh:accession`
5-methyltetrahydropteroyltri-L-glutamate `CHEBI:58207`	consumes	cobalamin-independent methionine synthase reaction `RHEA:21197`	RHEA:21197 Source assertion: Rhea lists CHEBI:58207 on the substrates side of RHEA:21197 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21197']/rh:substrates; rh:contains/rh:compound/rh:accession`
cobalamin-independent methionine synthase reaction `RHEA:21197`	produces	L-methionine `CHEBI:57844`	RHEA:21197 Source assertion: Rhea lists CHEBI:57844 on the products side of RHEA:21197 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21197']/rh:products; rh:contains/rh:compound/rh:accession`
cobalamin-independent methionine synthase reaction `RHEA:21197`	produces	tetrahydropteroyltri-L-glutamate `CHEBI:58140`	RHEA:21197 Source assertion: Rhea lists CHEBI:58140 on the products side of RHEA:21197 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21197']/rh:products; rh:contains/rh:compound/rh:accession`
L,L-cystathionine `CHEBI:58161`	consumes	L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	RHEA:43021 Source assertion: Rhea lists CHEBI:58161 on the substrates side of RHEA:43021 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/43021']/rh:substrates; rh:contains/rh:compound/rh:accession`
L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	produces	L-homocysteine `CHEBI:58199`	RHEA:43021 Source assertion: Rhea lists CHEBI:58199 on the products side of RHEA:43021 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/43021']/rh:products; rh:contains/rh:compound/rh:accession`
L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	produces	2-ammonioprop-2-enoate `CHEBI:76565`	RHEA:43021 Source assertion: Rhea lists CHEBI:76565 on the products side of RHEA:43021 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/43021']/rh:products; rh:contains/rh:compound/rh:accession`
2-ammonioprop-2-enoate `CHEBI:76565`	consumes	2-aminoprop-2-enoate => 2-iminopropanoate `RHEA:40668`	RHEA:40668 Source assertion: Rhea lists CHEBI:76565 on the substrates side of RHEA:40668 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40668']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-aminoprop-2-enoate => 2-iminopropanoate `RHEA:40668`	produces	2-iminiopropionate `CHEBI:44400`	RHEA:40668 Source assertion: Rhea lists CHEBI:44400 on the products side of RHEA:40668 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40668']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	RHEA:40672 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:40672 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40672']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-iminiopropionate `CHEBI:44400`	consumes	2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	RHEA:40672 Source assertion: Rhea lists CHEBI:44400 on the substrates side of RHEA:40672 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40672']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	produces	pyruvate `CHEBI:15361`	RHEA:40672 Source assertion: Rhea lists CHEBI:15361 on the products side of RHEA:40672 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40672']/rh:products; rh:contains/rh:compound/rh:accession`
2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	produces	NH4(+) `CHEBI:28938`	RHEA:40672 Source assertion: Rhea lists CHEBI:28938 on the products side of RHEA:40672 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/40672']/rh:products; rh:contains/rh:compound/rh:accession`
homoserine O-succinyltransferase `EC:2.3.1.46`	catalyzes	homoserine O-succinyltransferase reaction `RHEA:22009`	RHEA:22008 Source assertion: Rhea associates EC:2.3.1.46 with the reaction family containing RHEA:22009. Source location `rh:ec` PMID:10572016 Enzyme-catalyzed acylation of homoserine: mechanistic characterization of the Escherichia coli metA-encoded homoserine transsuccinylase. Source location `PubMed ArticleTitle`
cystathionine gamma-synthase `EC:2.5.1.48`	catalyzes	cystathionine gamma-synthase reaction `RHEA:20398`	RHEA:20397 Source assertion: Rhea associates EC:2.5.1.48 with the reaction family containing RHEA:20398. Source location `rh:ec` PMID:2405903 Purification and properties of cystathionine gamma-synthase from overproducing strains of Escherichia coli. Source location `PubMed ArticleTitle`
cystathionine beta-lyase MetC `UniProtKB:P06721`	catalyzes	L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: The native pathway assigns UniProtKB:P06721 activity to the enzymatic step represented by RHEA:43021; 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:7049234 Cloning, purification, and characterization of beta-cystathionase from Escherichia coli. Source location `PubMed ArticleTitle`
methionine synthase `EC:2.1.1.13`	catalyzes	cobalamin-dependent methionine synthase reaction `RHEA:11173`	RHEA:11172 Source assertion: Rhea associates EC:2.1.1.13 with the reaction family containing RHEA:11173. Source location `rh:ec` PMID:11731805 Domain alternation switches B(12)-dependent methionine synthase to the activation conformation. Source location `PubMed ArticleTitle`
5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase `EC:2.1.1.14`	catalyzes	cobalamin-independent methionine synthase reaction `RHEA:21197`	RHEA:21196 Source assertion: Rhea associates EC:2.1.1.14 with the reaction family containing RHEA:21197. Source location `rh:ec` PMID:8823155 Cobalamin-independent methionine synthase from Escherichia coli: a zinc metalloenzyme. Source location `PubMed ArticleTitle`
cystathionine gamma-synthase reaction `RHEA:20398`	precedes	L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:20398 before RHEA:43021 in this pathway. Shared intermediate: CHEBI:58161. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
homoserine O-succinyltransferase reaction `RHEA:22009`	precedes	cystathionine gamma-synthase reaction `RHEA:20398`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:22009 before RHEA:20398 in this pathway. Shared intermediate: CHEBI:57661. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
2-aminoprop-2-enoate => 2-iminopropanoate `RHEA:40668`	precedes	2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:40668 before RHEA:40672 in this pathway. Shared intermediate: CHEBI:44400. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	precedes	cobalamin-dependent methionine synthase reaction `RHEA:11173`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:43021 before RHEA:11173 in this pathway. Shared intermediate: CHEBI:58199. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	precedes	cobalamin-independent methionine synthase reaction `RHEA:21197`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:43021 before RHEA:21197 in this pathway. Shared intermediate: CHEBI:58199. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
L,L-cystathionine => L-homocysteine + 2-aminoprop-2-enoate `RHEA:43021`	precedes	2-aminoprop-2-enoate => 2-iminopropanoate `RHEA:40668`	MetaCyc:HOMOSER-METSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:43021 before RHEA:40668 in this pathway. Shared intermediate: CHEBI:76565. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
Cystathionine gamma-synthase `UniProtKB:P00935`	enables	cystathionine gamma-synthase reaction `RHEA:20398`	UniProtKB:P00935 Source assertion: UniProt annotates UniProtKB:P00935 with catalytic activity for the reaction family of RHEA:20398. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Cystathionine gamma-synthase `UniProtKB:P00935`	located_in	cytoplasm `GO:0005737`	UniProtKB:P00935 Source assertion: UniProt locates UniProtKB:P00935 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: curated source annotation. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
Cystathionine gamma-synthase `UniProtKB:P00935`	has_cofactor	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P00935 Source assertion: UniProt lists CHEBI:597326 as a cofactor of UniProtKB:P00935 (evidence: ECO:0000269). Binds 1 pyridoxal phosphate per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Homoserine O-succinyltransferase `UniProtKB:P07623`	enables	homoserine O-succinyltransferase reaction `RHEA:22009`	UniProtKB:P07623 Source assertion: UniProt annotates UniProtKB:P07623 with catalytic activity for the reaction family of RHEA:22009. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Homoserine O-succinyltransferase `UniProtKB:P07623`	located_in	cytoplasm `GO:0005737`	UniProtKB:P07623 Source assertion: UniProt locates UniProtKB:P07623 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000255, ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
2-iminobutanoate/2-iminopropanoate deaminase `UniProtKB:P0AF93`	enables	2-iminopropanoate + H2O => pyruvate + NH4(+) `RHEA:40672`	UniProtKB:P0AF93 Source assertion: UniProt annotates UniProtKB:P0AF93 with catalytic activity for the reaction family of RHEA:40672. Annotation evidence: curated source annotation; 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`
Methionine synthase `UniProtKB:P13009`	enables	cobalamin-dependent methionine synthase reaction `RHEA:11173`	UniProtKB:P13009 Source assertion: UniProt annotates UniProtKB:P13009 with catalytic activity for the reaction family of RHEA:11173. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Methionine synthase `UniProtKB:P13009`	has_cofactor	methylcobalamin `CHEBI:28115`	UniProtKB:P13009 Source assertion: UniProt lists CHEBI:28115 as a cofactor of UniProtKB:P13009 (evidence: ECO:0000269). Source location `comments[commentType='COFACTOR'].cofactors and note`
Methionine synthase `UniProtKB:P13009`	has_cofactor	zinc(2+) `CHEBI:29105`	UniProtKB:P13009 Source assertion: UniProt lists CHEBI:29105 as a cofactor of UniProtKB:P13009 (evidence: ECO:0000269). Binds 1 zinc ion per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase `UniProtKB:P25665`	enables	cobalamin-independent methionine synthase reaction `RHEA:21197`	UniProtKB:P25665 Source assertion: UniProt annotates UniProtKB:P25665 with catalytic activity for the reaction family of RHEA:21197. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase `UniProtKB:P25665`	has_cofactor	zinc(2+) `CHEBI:29105`	UniProtKB:P25665 Source assertion: UniProt lists CHEBI:29105 as a cofactor of UniProtKB:P25665 (evidence: ECO:0000255). Binds 1 zinc ion per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
cystathionine beta-lyase MetC `UniProtKB:P06721`	has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000269 (PubMed:3307782); ECO:0000269 (PubMed:7049234); ECO:0000269 (PubMed:8566238)	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P06721 Source assertion: UniProtKB:P06721 annotates CHEBI:597326 as a cofactor of this protein. Source location https://rest.uniprot.org/uniprotkb/stream?query=accession%3AP02918+OR+accession%3AP02919+OR+accession%3AP06721+OR+accession%3AP07862+OR+accession%3AP08373+OR+accession%3AP0A6B4+OR+accession%3AP0A6W3+OR+accession%3AP0A749+OR+accession%3AP0A759+OR+accession%3AP0ABG4+OR+accession%3AP0ACC7+OR+accession%3AP0AD68+OR+accession%3AP0AE16+OR+accession%3AP0AF16+OR+accession%3AP0AF18+OR+accession%3AP11880+OR+accession%3AP13016+OR+accession%3AP14900+OR+accession%3AP17169+OR+accession%3AP17443+OR+accession%3AP17952+OR+accession%3AP22188+OR+accession%3AP22634+OR+accession%3AP29012+OR+accession%3AP31120+OR+accession%3AP37773+OR+accession%3AP46022+OR+accession%3AP60932+OR+accession%3AP75949+OR+accession%3AP75959+OR+accession%3AP76008+OR+accession%3AP76535+OR+accession%3AP76577+OR+accession%3AP77272+OR+accession%3AP77570+OR+accession%3AP95189+OR+accession%3AP9WFZ5+OR+accession%3AP9WJM7+OR+accession%3AP9WJM9+OR+accession%3AP9WJN1+OR+accession%3AP9WKI1+OR+accession%3AP9WMY7+OR+accession%3AP9WN11+OR+accession%3AP9WQ19+OR+accession%3AP9WQ21+OR+accession%3AP9WQ23+OR+accession%3AQ2TL65&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_cofactor%2Corganism_id%2Ccc_caution [sha256:f2a2d9df603885068af58d89787438192b8c396d89a4cc931ac7bbab93a74c5c] #/results/2/comments/0/cofactors/0

References

MetaCyc:HOMOSER-METSYN-PWY MetaCyc L-methionine biosynthesis I pathway (source version: 22.5)
RHEA:22008 Rhea homoserine O-succinyltransferase reaction (source version: 139)
RHEA:22009 Rhea O-succinylhomoserine-forming homoserine O-succinyltransferase direction (source version: 139)
RHEA:20397 Rhea cystathionine gamma-synthase reaction (source version: 139)
RHEA:20398 Rhea L,L-cystathionine-forming cystathionine gamma-synthase direction (source version: 139)
RHEA:13965 Rhea cystathionine beta-lyase reaction (source version: 139)
RHEA:13966 Rhea L-homocysteine-forming cystathionine beta-lyase direction (source version: 139)
RHEA:11172 Rhea cobalamin-dependent methionine synthase reaction (source version: 139)
RHEA:11173 Rhea tetrahydrofolate-dependent L-methionine-forming methionine synthase direction (source version: 139)
RHEA:21196 Rhea cobalamin-independent methionine synthase reaction (source version: 139)
RHEA:21197 Rhea tetrahydropteroyltriglutamate-dependent L-methionine-forming methionine synthase direction (source version: 139)
UniProtKB:P06721 UniProtKB E. coli cystathionine beta-lyase MetC (source version: 2026_03)
PMID:10572016 Born and Blanchard, Biochemistry, 1999
PMID:2405903 Holbrook et al., Biochemistry, 1990
PMID:7049234 Dwivedi et al., Biochemistry, 1982
PMID:11731805 Bandarian et al., Nature Structural Biology, 2002
PMID:8823155 Gonzalez et al., Biochemistry, 1996
RHEA:43021 RHEA:43021 authority record (source version: 139)
RHEA:40668 RHEA:40668 authority record (source version: 139)
RHEA:40672 RHEA:40672 authority record (source version: 139)
UniProtKB:P00935 UniProtKB:P00935 authority record (source version: 2026_03)
UniProtKB:P07623 UniProtKB:P07623 authority record (source version: 2026_03)
UniProtKB:P0AF93 UniProtKB:P0AF93 authority record (source version: 2026_03)
UniProtKB:P13009 UniProtKB:P13009 authority record (source version: 2026_03)
UniProtKB:P25665 UniProtKB:P25665 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; 5 protein annotations, 4 cofactor annotations and 3 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:13966.
Read this curation session