L-histidine biosynthesis

MetaCyc:HISTSYN-PWY

5-phospho-alpha-D-ribose 1-diphosphate and ATP are converted to L-histidine through phosphoribosyl-ATP, phosphoribosyl-AMP, phosphoribulosylformimino-AICAR-phosphate, imidazole-glycerol phosphate, imidazole acetol-phosphate, L-histidinol phosphate, L-histidinol, and L-histidinal.

Pathway type

amino acid biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

Read the source YAML

Pathway network

54 nodes · 85 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.

Find a node

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
ATP phosphoribosyltransferase `EC:2.4.2.17`	molecular activity
phosphoribosyl-ATP diphosphatase `EC:3.6.1.31`	molecular activity
phosphoribosyl-AMP cyclohydrolase `EC:3.5.4.19`	molecular activity
phosphoribulosylformimino-AICAR-phosphate isomerase `EC:5.3.1.16`	molecular activity
imidazoleglycerol-phosphate synthase `EC:4.3.2.10`	molecular activity
imidazoleglycerol-phosphate dehydratase `EC:4.2.1.19`	molecular activity
histidinol-phosphate aminotransferase `EC:2.6.1.9`	molecular activity
histidinol-phosphatase `EC:3.1.3.15`	molecular activity
histidinol dehydrogenase `EC:1.1.1.23`	molecular activity
5-phospho-alpha-D-ribose 1-diphosphate `CHEBI:58017`	small molecule
ATP `CHEBI:30616`	small molecule
1-(5-phospho-beta-D-ribosyl)-ATP `CHEBI:73183`	small molecule
diphosphate `CHEBI:33019`	small molecule
H2O `CHEBI:15377`	small molecule
1-(5-phospho-beta-D-ribosyl)-5'-AMP `CHEBI:59457`	small molecule
H(+) `CHEBI:15378`	small molecule
1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide `CHEBI:58435`	small molecule
5-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide `CHEBI:58525`	small molecule
L-glutamine `CHEBI:58359`	small molecule
D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate `CHEBI:58278`	small molecule
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide `CHEBI:58475`	small molecule
L-glutamate `CHEBI:29985`	small molecule
3-(imidazol-4-yl)-2-oxopropyl phosphate `CHEBI:57766`	small molecule
L-histidinol phosphate `CHEBI:57980`	small molecule
2-oxoglutarate `CHEBI:16810`	small molecule
L-histidinol `CHEBI:57699`	small molecule
phosphate `CHEBI:43474`	small molecule
NAD(+) `CHEBI:57540`	small molecule
L-histidinal `CHEBI:64802`	small molecule
NADH `CHEBI:57945`	small molecule
L-histidine `CHEBI:57595`	small molecule
Histidinol-phosphate aminotransferase `UniProtKB:P06986`	protein
pyridoxal 5'-phosphate(2-) `CHEBI:597326`	cofactor
Histidine biosynthesis bifunctional protein HisB `UniProtKB:P06987`	protein
cytoplasm `GO:0005737`	cellular component
magnesium(2+) `CHEBI:18420`	cofactor
zinc(2+) `CHEBI:29105`	cofactor
Histidinol dehydrogenase `UniProtKB:P06988`	protein
Histidine biosynthesis bifunctional protein HisIE `UniProtKB:P06989`	protein
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase `UniProtKB:P10371`	protein
Imidazole glycerol phosphate synthase subunit HisH `UniProtKB:P60595`	protein
Imidazole glycerol phosphate synthase subunit HisF `UniProtKB:P60664`	protein
ATP phosphoribosyltransferase `UniProtKB:P60757`	protein
adenosine 5'-monophosphate(2-) `CHEBI:456215`	small molecule
ATP phosphoribosyltransferase reaction `RHEA:18475`	reaction	right to left
phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	reaction	left to right
phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	reaction	left to right
phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	reaction	left to right
imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	reaction	left to right
imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	reaction	left to right
histidinol-phosphate aminotransferase reaction `RHEA:23746`	reaction	right to left
histidinol-phosphatase reaction `RHEA:14466`	reaction	left to right
histidinol dehydrogenase first oxidation `RHEA:33800`	reaction	left to right
histidinal dehydrogenase reaction `RHEA:33804`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
ATP `CHEBI:30616`	consumes	ATP phosphoribosyltransferase reaction `RHEA:18475`	RHEA:18475 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:18475 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18475']/rh:substrates; rh:contains/rh:compound/rh:accession`
5-phospho-alpha-D-ribose 1-diphosphate `CHEBI:58017`	consumes	ATP phosphoribosyltransferase reaction `RHEA:18475`	RHEA:18475 Source assertion: Rhea lists CHEBI:58017 on the substrates side of RHEA:18475 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18475']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP phosphoribosyltransferase reaction `RHEA:18475`	produces	diphosphate `CHEBI:33019`	RHEA:18475 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:18475 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18475']/rh:products; rh:contains/rh:compound/rh:accession`
ATP phosphoribosyltransferase reaction `RHEA:18475`	produces	1-(5-phospho-beta-D-ribosyl)-ATP `CHEBI:73183`	RHEA:18475 Source assertion: Rhea lists CHEBI:73183 on the products side of RHEA:18475 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18475']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	RHEA:22829 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:22829 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22829']/rh:substrates; rh:contains/rh:compound/rh:accession`
1-(5-phospho-beta-D-ribosyl)-ATP `CHEBI:73183`	consumes	phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	RHEA:22829 Source assertion: Rhea lists CHEBI:73183 on the substrates side of RHEA:22829 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22829']/rh:substrates; rh:contains/rh:compound/rh:accession`
phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	produces	H(+) `CHEBI:15378`	RHEA:22829 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:22829 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22829']/rh:products; rh:contains/rh:compound/rh:accession`
phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	produces	diphosphate `CHEBI:33019`	RHEA:22829 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:22829 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22829']/rh:products; rh:contains/rh:compound/rh:accession`
phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	produces	1-(5-phospho-beta-D-ribosyl)-5'-AMP `CHEBI:59457`	RHEA:22829 Source assertion: Rhea lists CHEBI:59457 on the products side of RHEA:22829 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22829']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	RHEA:20050 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:20050 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20050']/rh:substrates; rh:contains/rh:compound/rh:accession`
1-(5-phospho-beta-D-ribosyl)-5'-AMP `CHEBI:59457`	consumes	phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	RHEA:20050 Source assertion: Rhea lists CHEBI:59457 on the substrates side of RHEA:20050 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20050']/rh:substrates; rh:contains/rh:compound/rh:accession`
phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	produces	1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide `CHEBI:58435`	RHEA:20050 Source assertion: Rhea lists CHEBI:58435 on the products side of RHEA:20050 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/20050']/rh:products; rh:contains/rh:compound/rh:accession`
1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide `CHEBI:58435`	consumes	phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	RHEA:15470 Source assertion: Rhea lists CHEBI:58435 on the substrates side of RHEA:15470 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15470']/rh:substrates; rh:contains/rh:compound/rh:accession`
phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	produces	5-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide `CHEBI:58525`	RHEA:15470 Source assertion: Rhea lists CHEBI:58525 on the products side of RHEA:15470 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15470']/rh:products; rh:contains/rh:compound/rh:accession`
L-glutamine `CHEBI:58359`	consumes	imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	RHEA:24794 Source assertion: Rhea lists CHEBI:58359 on the substrates side of RHEA:24794 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24794']/rh:substrates; rh:contains/rh:compound/rh:accession`
5-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide `CHEBI:58525`	consumes	imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	RHEA:24794 Source assertion: Rhea lists CHEBI:58525 on the substrates side of RHEA:24794 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24794']/rh:substrates; rh:contains/rh:compound/rh:accession`
imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	produces	H(+) `CHEBI:15378`	RHEA:24794 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:24794 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24794']/rh:products; rh:contains/rh:compound/rh:accession`
imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	produces	L-glutamate `CHEBI:29985`	RHEA:24794 Source assertion: Rhea lists CHEBI:29985 on the products side of RHEA:24794 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24794']/rh:products; rh:contains/rh:compound/rh:accession`
imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	produces	D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate `CHEBI:58278`	RHEA:24794 Source assertion: Rhea lists CHEBI:58278 on the products side of RHEA:24794 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24794']/rh:products; rh:contains/rh:compound/rh:accession`
imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	produces	5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide `CHEBI:58475`	RHEA:24794 Source assertion: Rhea lists CHEBI:58475 on the products side of RHEA:24794 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24794']/rh:products; rh:contains/rh:compound/rh:accession`
D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate `CHEBI:58278`	consumes	imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	RHEA:11041 Source assertion: Rhea lists CHEBI:58278 on the substrates side of RHEA:11041 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11041']/rh:substrates; rh:contains/rh:compound/rh:accession`
imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	produces	H2O `CHEBI:15377`	RHEA:11041 Source assertion: Rhea lists CHEBI:15377 on the products side of RHEA:11041 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11041']/rh:products; rh:contains/rh:compound/rh:accession`
imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	produces	3-(imidazol-4-yl)-2-oxopropyl phosphate `CHEBI:57766`	RHEA:11041 Source assertion: Rhea lists CHEBI:57766 on the products side of RHEA:11041 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11041']/rh:products; rh:contains/rh:compound/rh:accession`
L-glutamate `CHEBI:29985`	consumes	histidinol-phosphate aminotransferase reaction `RHEA:23746`	RHEA:23746 Source assertion: Rhea lists CHEBI:29985 on the substrates side of RHEA:23746 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23746']/rh:substrates; rh:contains/rh:compound/rh:accession`
3-(imidazol-4-yl)-2-oxopropyl phosphate `CHEBI:57766`	consumes	histidinol-phosphate aminotransferase reaction `RHEA:23746`	RHEA:23746 Source assertion: Rhea lists CHEBI:57766 on the substrates side of RHEA:23746 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23746']/rh:substrates; rh:contains/rh:compound/rh:accession`
histidinol-phosphate aminotransferase reaction `RHEA:23746`	produces	2-oxoglutarate `CHEBI:16810`	RHEA:23746 Source assertion: Rhea lists CHEBI:16810 on the products side of RHEA:23746 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23746']/rh:products; rh:contains/rh:compound/rh:accession`
histidinol-phosphate aminotransferase reaction `RHEA:23746`	produces	L-histidinol phosphate `CHEBI:57980`	RHEA:23746 Source assertion: Rhea lists CHEBI:57980 on the products side of RHEA:23746 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23746']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	histidinol-phosphatase reaction `RHEA:14466`	RHEA:14466 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:14466 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14466']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-histidinol phosphate `CHEBI:57980`	consumes	histidinol-phosphatase reaction `RHEA:14466`	RHEA:14466 Source assertion: Rhea lists CHEBI:57980 on the substrates side of RHEA:14466 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14466']/rh:substrates; rh:contains/rh:compound/rh:accession`
histidinol-phosphatase reaction `RHEA:14466`	produces	phosphate `CHEBI:43474`	RHEA:14466 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:14466 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14466']/rh:products; rh:contains/rh:compound/rh:accession`
histidinol-phosphatase reaction `RHEA:14466`	produces	L-histidinol `CHEBI:57699`	RHEA:14466 Source assertion: Rhea lists CHEBI:57699 on the products side of RHEA:14466 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14466']/rh:products; rh:contains/rh:compound/rh:accession`
NAD(+) `CHEBI:57540`	consumes	histidinol dehydrogenase first oxidation `RHEA:33800`	RHEA:33800 Source assertion: Rhea lists CHEBI:57540 on the substrates side of RHEA:33800 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33800']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-histidinol `CHEBI:57699`	consumes	histidinol dehydrogenase first oxidation `RHEA:33800`	RHEA:33800 Source assertion: Rhea lists CHEBI:57699 on the substrates side of RHEA:33800 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33800']/rh:substrates; rh:contains/rh:compound/rh:accession`
histidinol dehydrogenase first oxidation `RHEA:33800`	produces	H(+) `CHEBI:15378`	RHEA:33800 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:33800 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33800']/rh:products; rh:contains/rh:compound/rh:accession`
histidinol dehydrogenase first oxidation `RHEA:33800`	produces	NADH `CHEBI:57945`	RHEA:33800 Source assertion: Rhea lists CHEBI:57945 on the products side of RHEA:33800 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33800']/rh:products; rh:contains/rh:compound/rh:accession`
histidinol dehydrogenase first oxidation `RHEA:33800`	produces	L-histidinal `CHEBI:64802`	RHEA:33800 Source assertion: Rhea lists CHEBI:64802 on the products side of RHEA:33800 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33800']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	histidinal dehydrogenase reaction `RHEA:33804`	RHEA:33804 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:33804 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33804']/rh:substrates; rh:contains/rh:compound/rh:accession`
NAD(+) `CHEBI:57540`	consumes	histidinal dehydrogenase reaction `RHEA:33804`	RHEA:33804 Source assertion: Rhea lists CHEBI:57540 on the substrates side of RHEA:33804 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33804']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-histidinal `CHEBI:64802`	consumes	histidinal dehydrogenase reaction `RHEA:33804`	RHEA:33804 Source assertion: Rhea lists CHEBI:64802 on the substrates side of RHEA:33804 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33804']/rh:substrates; rh:contains/rh:compound/rh:accession`
histidinal dehydrogenase reaction `RHEA:33804`	produces	H(+) `CHEBI:15378`	RHEA:33804 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:33804 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33804']/rh:products; rh:contains/rh:compound/rh:accession`
histidinal dehydrogenase reaction `RHEA:33804`	produces	L-histidine `CHEBI:57595`	RHEA:33804 Source assertion: Rhea lists CHEBI:57595 on the products side of RHEA:33804 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33804']/rh:products; rh:contains/rh:compound/rh:accession`
histidinal dehydrogenase reaction `RHEA:33804`	produces	NADH `CHEBI:57945`	RHEA:33804 Source assertion: Rhea lists CHEBI:57945 on the products side of RHEA:33804 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33804']/rh:products; rh:contains/rh:compound/rh:accession`
ATP phosphoribosyltransferase `EC:2.4.2.17`	catalyzes	ATP phosphoribosyltransferase reaction `RHEA:18475`	RHEA:18473 Source assertion: Rhea associates EC:2.4.2.17 with the reaction family containing RHEA:18475. Source location `rh:ec`
phosphoribosyl-ATP diphosphatase `EC:3.6.1.31`	catalyzes	phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	RHEA:22828 Source assertion: Rhea associates EC:3.6.1.31 with the reaction family containing RHEA:22829. Source location `rh:ec`
phosphoribosyl-AMP cyclohydrolase `EC:3.5.4.19`	catalyzes	phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	RHEA:20049 Source assertion: Rhea associates EC:3.5.4.19 with the reaction family containing RHEA:20050. Source location `rh:ec`
phosphoribulosylformimino-AICAR-phosphate isomerase `EC:5.3.1.16`	catalyzes	phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	RHEA:15469 Source assertion: Rhea associates EC:5.3.1.16 with the reaction family containing RHEA:15470. Source location `rh:ec`
imidazoleglycerol-phosphate synthase `EC:4.3.2.10`	catalyzes	imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	RHEA:24793 Source assertion: Rhea associates EC:4.3.2.10 with the reaction family containing RHEA:24794. Source location `rh:ec`
imidazoleglycerol-phosphate dehydratase `EC:4.2.1.19`	catalyzes	imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	RHEA:11040 Source assertion: Rhea associates EC:4.2.1.19 with the reaction family containing RHEA:11041. Source location `rh:ec`
histidinol-phosphate aminotransferase `EC:2.6.1.9`	catalyzes	histidinol-phosphate aminotransferase reaction `RHEA:23746`	RHEA:23744 Source assertion: Rhea associates EC:2.6.1.9 with the reaction family containing RHEA:23746. Source location `rh:ec`
histidinol-phosphatase `EC:3.1.3.15`	catalyzes	histidinol-phosphatase reaction `RHEA:14466`	RHEA:14465 Source assertion: Rhea associates EC:3.1.3.15 with the reaction family containing RHEA:14466. Source location `rh:ec`
histidinol dehydrogenase `EC:1.1.1.23`	catalyzes	histidinol dehydrogenase first oxidation `RHEA:33800`	MetaCyc:HISTSYN-PWY Source assertion: The native pathway assigns EC:1.1.1.23 activity to the enzymatic step represented by RHEA:33800; 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:11842181 Source assertion: The study describes E. coli HisD catalyzing sequential NAD-dependent oxidations of histidinol to histidinaldehyde and then histidine. Source location `PubMed Abstract; sequential HisD reactions`
histidinol dehydrogenase `EC:1.1.1.23`	catalyzes	histidinal dehydrogenase reaction `RHEA:33804`	MetaCyc:HISTSYN-PWY Source assertion: The native pathway assigns EC:1.1.1.23 activity to the enzymatic step represented by RHEA:33804; 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:11842181 Source assertion: The study describes E. coli HisD catalyzing sequential NAD-dependent oxidations of histidinol to histidinaldehyde and then histidine. Source location `PubMed Abstract; sequential HisD reactions`
imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	precedes	histidinol-phosphate aminotransferase reaction `RHEA:23746`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:11041 before RHEA:23746 in this pathway. Shared intermediate: CHEBI:57766. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
histidinol-phosphatase reaction `RHEA:14466`	precedes	histidinol dehydrogenase first oxidation `RHEA:33800`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:14466 before RHEA:33800 in this pathway. Shared intermediate: CHEBI:57699. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	precedes	imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:15470 before RHEA:24794 in this pathway. Shared intermediate: CHEBI:58525. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
ATP phosphoribosyltransferase reaction `RHEA:18475`	precedes	phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:18475 before RHEA:22829 in this pathway. Shared intermediate: CHEBI:73183. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	precedes	phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:20050 before RHEA:15470 in this pathway. Shared intermediate: CHEBI:58435. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	precedes	phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:22829 before RHEA:20050 in this pathway. Shared intermediate: CHEBI:59457. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
histidinol-phosphate aminotransferase reaction `RHEA:23746`	precedes	histidinol-phosphatase reaction `RHEA:14466`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:23746 before RHEA:14466 in this pathway. Shared intermediate: CHEBI:57980. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	precedes	imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:24794 before RHEA:11041 in this pathway. Shared intermediate: CHEBI:58278. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
histidinol dehydrogenase first oxidation `RHEA:33800`	precedes	histidinal dehydrogenase reaction `RHEA:33804`	MetaCyc:HISTSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:33800 before RHEA:33804 in this pathway. Shared intermediate: CHEBI:64802. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
Histidinol-phosphate aminotransferase `UniProtKB:P06986`	enables	histidinol-phosphate aminotransferase reaction `RHEA:23746`	UniProtKB:P06986 Source assertion: UniProt annotates UniProtKB:P06986 with catalytic activity for the reaction family of RHEA:23746. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidinol-phosphate aminotransferase `UniProtKB:P06986`	has_cofactor	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P06986 Source assertion: UniProt lists CHEBI:597326 as a cofactor of UniProtKB:P06986 (evidence: ECO:0000269). Source location `comments[commentType='COFACTOR'].cofactors and note`
Histidine biosynthesis bifunctional protein HisB `UniProtKB:P06987`	enables	imidazoleglycerol-phosphate dehydratase reaction `RHEA:11041`	UniProtKB:P06987 Source assertion: UniProt annotates UniProtKB:P06987 with catalytic activity for the reaction family of RHEA:11041. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidine biosynthesis bifunctional protein HisB `UniProtKB:P06987`	enables	histidinol-phosphatase reaction `RHEA:14466`	UniProtKB:P06987 Source assertion: UniProt annotates UniProtKB:P06987 with catalytic activity for the reaction family of RHEA:14466. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidine biosynthesis bifunctional protein HisB `UniProtKB:P06987`	located_in	cytoplasm `GO:0005737`	UniProtKB:P06987 Source assertion: UniProt locates UniProtKB:P06987 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`
Histidine biosynthesis bifunctional protein HisB `UniProtKB:P06987`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P06987 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P06987 (evidence: ECO:0000255). Source location `comments[commentType='COFACTOR'].cofactors and note`
Histidine biosynthesis bifunctional protein HisB `UniProtKB:P06987`	has_cofactor	zinc(2+) `CHEBI:29105`	UniProtKB:P06987 Source assertion: UniProt lists CHEBI:29105 as a cofactor of UniProtKB:P06987 (evidence: ECO:0000255). Source location `comments[commentType='COFACTOR'].cofactors and note`
Histidinol dehydrogenase `UniProtKB:P06988`	enables	histidinol dehydrogenase first oxidation `RHEA:33800`	UniProtKB:P06988 Source assertion: UniProt annotates UniProtKB:P06988 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:33800. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidinol dehydrogenase `UniProtKB:P06988`	enables	histidinal dehydrogenase reaction `RHEA:33804`	UniProtKB:P06988 Source assertion: UniProt annotates UniProtKB:P06988 with catalytic activity for the overall reaction containing the native MetaCyc enzymatic component RHEA:33804. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidinol dehydrogenase `UniProtKB:P06988`	has_cofactor	zinc(2+) `CHEBI:29105`	UniProtKB:P06988 Source assertion: UniProt lists CHEBI:29105 as a cofactor of UniProtKB:P06988 (evidence: ECO:0000269). Binds 1 zinc ion per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Histidine biosynthesis bifunctional protein HisIE `UniProtKB:P06989`	enables	phosphoribosyl-ATP diphosphatase reaction `RHEA:22829`	UniProtKB:P06989 Source assertion: UniProt annotates UniProtKB:P06989 with catalytic activity for the reaction family of RHEA:22829. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidine biosynthesis bifunctional protein HisIE `UniProtKB:P06989`	enables	phosphoribosyl-AMP cyclohydrolase reaction `RHEA:20050`	UniProtKB:P06989 Source assertion: UniProt annotates UniProtKB:P06989 with catalytic activity for the reaction family of RHEA:20050. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Histidine biosynthesis bifunctional protein HisIE `UniProtKB:P06989`	located_in	cytoplasm `GO:0005737`	UniProtKB:P06989 Source assertion: UniProt locates UniProtKB:P06989 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`
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase `UniProtKB:P10371`	enables	phosphoribulosylformimino-AICAR-phosphate isomerase reaction `RHEA:15470`	UniProtKB:P10371 Source assertion: UniProt annotates UniProtKB:P10371 with catalytic activity for the reaction family of RHEA:15470. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase `UniProtKB:P10371`	located_in	cytoplasm `GO:0005737`	UniProtKB:P10371 Source assertion: UniProt locates UniProtKB:P10371 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`
Imidazole glycerol phosphate synthase subunit HisH `UniProtKB:P60595`	enables	imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	UniProtKB:P60595 Source assertion: UniProt annotates UniProtKB:P60595 with catalytic activity for the reaction family of RHEA:24794. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Imidazole glycerol phosphate synthase subunit HisH `UniProtKB:P60595`	located_in	cytoplasm `GO:0005737`	UniProtKB:P60595 Source assertion: UniProt locates UniProtKB:P60595 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`
Imidazole glycerol phosphate synthase subunit HisF `UniProtKB:P60664`	enables	imidazoleglycerol-phosphate synthase reaction `RHEA:24794`	UniProtKB:P60664 Source assertion: UniProt annotates UniProtKB:P60664 with catalytic activity for the reaction family of RHEA:24794. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Imidazole glycerol phosphate synthase subunit HisF `UniProtKB:P60664`	located_in	cytoplasm `GO:0005737`	UniProtKB:P60664 Source assertion: UniProt locates UniProtKB:P60664 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`
ATP phosphoribosyltransferase `UniProtKB:P60757`	enables	ATP phosphoribosyltransferase reaction `RHEA:18475`	UniProtKB:P60757 Source assertion: UniProt annotates UniProtKB:P60757 with catalytic activity for the reaction family of RHEA:18475. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
L-histidine `CHEBI:57595`	inhibits	ATP phosphoribosyltransferase `UniProtKB:P60757`	UniProtKB:P60757 Source assertion: UniProt activity-regulation annotation: Feedback inhibited by histidine. Also inhibited by AMP and PR-ATP Source location `comments[commentType='ACTIVITY REGULATION'].texts`
adenosine 5'-monophosphate(2-) `CHEBI:456215`	inhibits	ATP phosphoribosyltransferase `UniProtKB:P60757`	UniProtKB:P60757 Source assertion: UniProt activity-regulation annotation: Feedback inhibited by histidine. Also inhibited by AMP and PR-ATP Source location `comments[commentType='ACTIVITY REGULATION'].texts`
ATP phosphoribosyltransferase `UniProtKB:P60757`	located_in	cytoplasm `GO:0005737`	UniProtKB:P60757 Source assertion: UniProt locates UniProtKB:P60757 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`
ATP phosphoribosyltransferase `UniProtKB:P60757`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P60757 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P60757 (evidence: ECO:0000305). Source location `comments[commentType='COFACTOR'].cofactors and note`

References

MetaCyc:HISTSYN-PWY MetaCyc L-histidine biosynthesis pathway (source version: 22.5)
RHEA:18473 Rhea ATP phosphoribosyltransferase reaction (source version: 139)
RHEA:18475 Rhea 1-(5-phospho-beta-D-ribosyl)-ATP-forming direction (source version: 139)
RHEA:22828 Rhea phosphoribosyl-ATP diphosphatase reaction (source version: 139)
RHEA:22829 Rhea phosphoribosyl-AMP-forming direction (source version: 139)
RHEA:20049 Rhea phosphoribosyl-AMP cyclohydrolase reaction (source version: 139)
RHEA:20050 Rhea phosphoribulosylformimino-AICAR-phosphate-forming direction (source version: 139)
RHEA:15469 Rhea phosphoribulosylformimino-AICAR-phosphate isomerase reaction (source version: 139)
RHEA:15470 Rhea phosphoribulosylformimino-AICAR-phosphate-forming direction (source version: 139)
RHEA:24793 Rhea imidazoleglycerol-phosphate synthase reaction (source version: 139)
RHEA:24794 Rhea imidazoleglycerol-phosphate-forming direction (source version: 139)
RHEA:11040 Rhea imidazoleglycerol-phosphate dehydratase reaction (source version: 139)
RHEA:11041 Rhea imidazole acetol-phosphate-forming direction (source version: 139)
RHEA:23744 Rhea histidinol-phosphate aminotransferase reaction (source version: 139)
RHEA:23746 Rhea L-histidinol-phosphate-forming direction (source version: 139)
RHEA:14465 Rhea histidinol-phosphatase reaction (source version: 139)
RHEA:14466 Rhea L-histidinol-forming direction (source version: 139)
RHEA:33799 Rhea L-histidinal-forming histidinol dehydrogenase half-reaction (source version: 139)
RHEA:33800 Rhea L-histidinal-forming direction (source version: 139)
RHEA:33803 Rhea L-histidine-forming histidinal dehydrogenase half-reaction (source version: 139)
RHEA:33804 Rhea L-histidine-forming direction (source version: 139)
PMID:11842181 Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase
UniProtKB:P06986 UniProtKB:P06986 authority record (source version: 2026_03)
UniProtKB:P06987 UniProtKB:P06987 authority record (source version: 2026_03)
UniProtKB:P06988 UniProtKB:P06988 authority record (source version: 2026_03)
UniProtKB:P06989 UniProtKB:P06989 authority record (source version: 2026_03)
UniProtKB:P10371 UniProtKB:P10371 authority record (source version: 2026_03)
UniProtKB:P60595 UniProtKB:P60595 authority record (source version: 2026_03)
UniProtKB:P60664 UniProtKB:P60664 authority record (source version: 2026_03)
UniProtKB:P60757 UniProtKB:P60757 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 10 to 10; 0 directed-ID corrections; 8 protein annotations, 5 cofactor annotations and 6 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.
Read this curation session