L-arginine biosynthesis I (via L-ornithine)

MetaCyc:ARGSYN-PWY

L-arginine biosynthesis I acetylates L-glutamate, reduces the phosphorylated acetylglutamate through N-acetyl-L-glutamate 5-semialdehyde, transaminates it to N(2)-acetyl-L-ornithine, deacetylates L-ornithine, and converts L-ornithine through L-citrulline and argininosuccinate to L-arginine.

Pathway type

amino acid biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

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Pathway network

63 nodes · 91 asserted directed edges

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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
N-acetylglutamate synthase `EC:2.3.1.1`	molecular activity
acetylglutamate kinase `EC:2.7.2.8`	molecular activity
N-acetyl-gamma-glutamyl-phosphate reductase `EC:1.2.1.38`	molecular activity
acetylornithine aminotransferase `EC:2.6.1.11`	molecular activity
acetylornithine deacetylase `EC:3.5.1.16`	molecular activity
ornithine carbamoyltransferase `EC:2.1.3.3`	molecular activity
argininosuccinate synthase `EC:6.3.4.5`	molecular activity
argininosuccinate lyase `EC:4.3.2.1`	molecular activity
L-glutamate `CHEBI:29985`	small molecule
acetyl-CoA `CHEBI:57288`	small molecule
N-acetyl-L-glutamate `CHEBI:44337`	small molecule
CoA `CHEBI:57287`	small molecule
H(+) `CHEBI:15378`	small molecule
ATP `CHEBI:30616`	small molecule
N-acetyl-L-glutamyl 5-phosphate `CHEBI:57936`	small molecule
ADP `CHEBI:456216`	small molecule
NADPH `CHEBI:57783`	small molecule
N-acetyl-L-glutamate 5-semialdehyde `CHEBI:29123`	small molecule
phosphate `CHEBI:43474`	small molecule
NADP(+) `CHEBI:58349`	small molecule
N(2)-acetyl-L-ornithine `CHEBI:57805`	small molecule
2-oxoglutarate `CHEBI:16810`	small molecule
H2O `CHEBI:15377`	small molecule
L-ornithine `CHEBI:46911`	small molecule
acetate `CHEBI:30089`	small molecule
carbamoyl phosphate `CHEBI:58228`	small molecule
L-citrulline `CHEBI:57743`	small molecule
L-aspartate `CHEBI:29991`	small molecule
2-(N(omega)-L-arginino)succinate `CHEBI:57472`	small molecule
AMP `CHEBI:456215`	small molecule
diphosphate `CHEBI:33019`	small molecule
fumarate `CHEBI:29806`	small molecule
L-arginine `CHEBI:32682`	small molecule
carbamoyl-phosphate synthase (glutamine-hydrolyzing) `EC:6.3.5.5`	molecular activity
hydrogencarbonate `CHEBI:17544`	small molecule
L-glutamine zwitterion `CHEBI:58359`	small molecule
Carbamoyl phosphate synthase large chain `UniProtKB:P00968`	protein
magnesium(2+) `CHEBI:18420`	cofactor
manganese(2+) `CHEBI:29035`	cofactor
Ornithine carbamoyltransferase subunit I `UniProtKB:P04391`	protein
cytoplasm `GO:0005737`	cellular component
Ornithine carbamoyltransferase subunit F `UniProtKB:P06960`	protein
Amino-acid acetyltransferase `UniProtKB:P0A6C5`	protein
Acetylglutamate kinase `UniProtKB:P0A6C8`	protein
Argininosuccinate synthase `UniProtKB:P0A6E4`	protein
Carbamoyl phosphate synthase small chain `UniProtKB:P0A6F1`	protein
N-acetyl-gamma-glutamyl-phosphate reductase `UniProtKB:P11446`	protein
Argininosuccinate lyase `UniProtKB:P11447`	protein
Acetylornithine/succinyldiaminopimelate aminotransferase `UniProtKB:P18335`	protein
pyridoxal 5'-phosphate(2-) `CHEBI:597326`	cofactor
Acetylornithine deacetylase `UniProtKB:P23908`	protein
zinc(2+) `CHEBI:29105`	cofactor
cobalt(2+) `CHEBI:48828`	cofactor
glutathionate(1-) `CHEBI:57925`	cofactor
N-acetylglutamate synthase reaction `RHEA:24293`	reaction	left to right
N-acetylglutamate kinase reaction `RHEA:14630`	reaction	left to right
N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	reaction	right to left
acetylornithine aminotransferase reaction `RHEA:18051`	reaction	right to left
acetylornithine deacetylase reaction `RHEA:15942`	reaction	left to right
ornithine carbamoyltransferase reaction `RHEA:19514`	reaction	left to right
argininosuccinate synthase reaction `RHEA:10933`	reaction	left to right
argininosuccinate lyase reaction `RHEA:24021`	reaction	left to right
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
L-glutamate `CHEBI:29985`	consumes	N-acetylglutamate synthase reaction `RHEA:24293`	RHEA:24293 Source assertion: Rhea lists CHEBI:29985 on the substrates side of RHEA:24293 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24293']/rh:substrates; rh:contains/rh:compound/rh:accession`
acetyl-CoA `CHEBI:57288`	consumes	N-acetylglutamate synthase reaction `RHEA:24293`	RHEA:24293 Source assertion: Rhea lists CHEBI:57288 on the substrates side of RHEA:24293 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24293']/rh:substrates; rh:contains/rh:compound/rh:accession`
N-acetylglutamate synthase reaction `RHEA:24293`	produces	H(+) `CHEBI:15378`	RHEA:24293 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:24293 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24293']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetylglutamate synthase reaction `RHEA:24293`	produces	N-acetyl-L-glutamate `CHEBI:44337`	RHEA:24293 Source assertion: Rhea lists CHEBI:44337 on the products side of RHEA:24293 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24293']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetylglutamate synthase reaction `RHEA:24293`	produces	CoA `CHEBI:57287`	RHEA:24293 Source assertion: Rhea lists CHEBI:57287 on the products side of RHEA:24293 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24293']/rh:products; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	N-acetylglutamate kinase reaction `RHEA:14630`	RHEA:14630 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:14630 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14630']/rh:substrates; rh:contains/rh:compound/rh:accession`
N-acetyl-L-glutamate `CHEBI:44337`	consumes	N-acetylglutamate kinase reaction `RHEA:14630`	RHEA:14630 Source assertion: Rhea lists CHEBI:44337 on the substrates side of RHEA:14630 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14630']/rh:substrates; rh:contains/rh:compound/rh:accession`
N-acetylglutamate kinase reaction `RHEA:14630`	produces	ADP `CHEBI:456216`	RHEA:14630 Source assertion: Rhea lists CHEBI:456216 on the products side of RHEA:14630 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14630']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetylglutamate kinase reaction `RHEA:14630`	produces	N-acetyl-L-glutamyl 5-phosphate `CHEBI:57936`	RHEA:14630 Source assertion: Rhea lists CHEBI:57936 on the products side of RHEA:14630 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14630']/rh:products; rh:contains/rh:compound/rh:accession`
H(+) `CHEBI:15378`	consumes	N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	RHEA:21590 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:21590 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21590']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH `CHEBI:57783`	consumes	N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	RHEA:21590 Source assertion: Rhea lists CHEBI:57783 on the substrates side of RHEA:21590 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21590']/rh:substrates; rh:contains/rh:compound/rh:accession`
N-acetyl-L-glutamyl 5-phosphate `CHEBI:57936`	consumes	N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	RHEA:21590 Source assertion: Rhea lists CHEBI:57936 on the substrates side of RHEA:21590 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21590']/rh:substrates; rh:contains/rh:compound/rh:accession`
N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	produces	N-acetyl-L-glutamate 5-semialdehyde `CHEBI:29123`	RHEA:21590 Source assertion: Rhea lists CHEBI:29123 on the products side of RHEA:21590 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21590']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	produces	phosphate `CHEBI:43474`	RHEA:21590 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:21590 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21590']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	produces	NADP(+) `CHEBI:58349`	RHEA:21590 Source assertion: Rhea lists CHEBI:58349 on the products side of RHEA:21590 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21590']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetyl-L-glutamate 5-semialdehyde `CHEBI:29123`	consumes	acetylornithine aminotransferase reaction `RHEA:18051`	RHEA:18051 Source assertion: Rhea lists CHEBI:29123 on the substrates side of RHEA:18051 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18051']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-glutamate `CHEBI:29985`	consumes	acetylornithine aminotransferase reaction `RHEA:18051`	RHEA:18051 Source assertion: Rhea lists CHEBI:29985 on the substrates side of RHEA:18051 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18051']/rh:substrates; rh:contains/rh:compound/rh:accession`
acetylornithine aminotransferase reaction `RHEA:18051`	produces	2-oxoglutarate `CHEBI:16810`	RHEA:18051 Source assertion: Rhea lists CHEBI:16810 on the products side of RHEA:18051 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18051']/rh:products; rh:contains/rh:compound/rh:accession`
acetylornithine aminotransferase reaction `RHEA:18051`	produces	N(2)-acetyl-L-ornithine `CHEBI:57805`	RHEA:18051 Source assertion: Rhea lists CHEBI:57805 on the products side of RHEA:18051 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18051']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	acetylornithine deacetylase reaction `RHEA:15942`	RHEA:15942 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:15942 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15942']/rh:substrates; rh:contains/rh:compound/rh:accession`
N(2)-acetyl-L-ornithine `CHEBI:57805`	consumes	acetylornithine deacetylase reaction `RHEA:15942`	RHEA:15942 Source assertion: Rhea lists CHEBI:57805 on the substrates side of RHEA:15942 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15942']/rh:substrates; rh:contains/rh:compound/rh:accession`
acetylornithine deacetylase reaction `RHEA:15942`	produces	acetate `CHEBI:30089`	RHEA:15942 Source assertion: Rhea lists CHEBI:30089 on the products side of RHEA:15942 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15942']/rh:products; rh:contains/rh:compound/rh:accession`
acetylornithine deacetylase reaction `RHEA:15942`	produces	L-ornithine `CHEBI:46911`	RHEA:15942 Source assertion: Rhea lists CHEBI:46911 on the products side of RHEA:15942 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15942']/rh:products; rh:contains/rh:compound/rh:accession`
L-ornithine `CHEBI:46911`	consumes	ornithine carbamoyltransferase reaction `RHEA:19514`	RHEA:19514 Source assertion: Rhea lists CHEBI:46911 on the substrates side of RHEA:19514 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/19514']/rh:substrates; rh:contains/rh:compound/rh:accession`
carbamoyl phosphate `CHEBI:58228`	consumes	ornithine carbamoyltransferase reaction `RHEA:19514`	RHEA:19514 Source assertion: Rhea lists CHEBI:58228 on the substrates side of RHEA:19514 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/19514']/rh:substrates; rh:contains/rh:compound/rh:accession`
ornithine carbamoyltransferase reaction `RHEA:19514`	produces	H(+) `CHEBI:15378`	RHEA:19514 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:19514 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/19514']/rh:products; rh:contains/rh:compound/rh:accession`
ornithine carbamoyltransferase reaction `RHEA:19514`	produces	phosphate `CHEBI:43474`	RHEA:19514 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:19514 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/19514']/rh:products; rh:contains/rh:compound/rh:accession`
ornithine carbamoyltransferase reaction `RHEA:19514`	produces	L-citrulline `CHEBI:57743`	RHEA:19514 Source assertion: Rhea lists CHEBI:57743 on the products side of RHEA:19514 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/19514']/rh:products; rh:contains/rh:compound/rh:accession`
L-aspartate `CHEBI:29991`	consumes	argininosuccinate synthase reaction `RHEA:10933`	RHEA:10933 Source assertion: Rhea lists CHEBI:29991 on the substrates side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	argininosuccinate synthase reaction `RHEA:10933`	RHEA:10933 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-citrulline `CHEBI:57743`	consumes	argininosuccinate synthase reaction `RHEA:10933`	RHEA:10933 Source assertion: Rhea lists CHEBI:57743 on the substrates side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:substrates; rh:contains/rh:compound/rh:accession`
argininosuccinate synthase reaction `RHEA:10933`	produces	H(+) `CHEBI:15378`	RHEA:10933 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:products; rh:contains/rh:compound/rh:accession`
argininosuccinate synthase reaction `RHEA:10933`	produces	diphosphate `CHEBI:33019`	RHEA:10933 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:products; rh:contains/rh:compound/rh:accession`
argininosuccinate synthase reaction `RHEA:10933`	produces	AMP `CHEBI:456215`	RHEA:10933 Source assertion: Rhea lists CHEBI:456215 on the products side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:products; rh:contains/rh:compound/rh:accession`
argininosuccinate synthase reaction `RHEA:10933`	produces	2-(N(omega)-L-arginino)succinate `CHEBI:57472`	RHEA:10933 Source assertion: Rhea lists CHEBI:57472 on the products side of RHEA:10933 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10933']/rh:products; rh:contains/rh:compound/rh:accession`
2-(N(omega)-L-arginino)succinate `CHEBI:57472`	consumes	argininosuccinate lyase reaction `RHEA:24021`	RHEA:24021 Source assertion: Rhea lists CHEBI:57472 on the substrates side of RHEA:24021 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24021']/rh:substrates; rh:contains/rh:compound/rh:accession`
argininosuccinate lyase reaction `RHEA:24021`	produces	fumarate `CHEBI:29806`	RHEA:24021 Source assertion: Rhea lists CHEBI:29806 on the products side of RHEA:24021 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24021']/rh:products; rh:contains/rh:compound/rh:accession`
argininosuccinate lyase reaction `RHEA:24021`	produces	L-arginine `CHEBI:32682`	RHEA:24021 Source assertion: Rhea lists CHEBI:32682 on the products side of RHEA:24021 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24021']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	RHEA:18634 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:substrates; rh:contains/rh:compound/rh:accession`
hydrogencarbonate `CHEBI:17544`	consumes	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	RHEA:18634 Source assertion: Rhea lists CHEBI:17544 on the substrates side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	RHEA:18634 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-glutamine zwitterion `CHEBI:58359`	consumes	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	RHEA:18634 Source assertion: Rhea lists CHEBI:58359 on the substrates side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:substrates; rh:contains/rh:compound/rh:accession`
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	produces	H(+) `CHEBI:15378`	RHEA:18634 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:products; rh:contains/rh:compound/rh:accession`
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	produces	L-glutamate `CHEBI:29985`	RHEA:18634 Source assertion: Rhea lists CHEBI:29985 on the products side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:products; rh:contains/rh:compound/rh:accession`
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	produces	phosphate `CHEBI:43474`	RHEA:18634 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:products; rh:contains/rh:compound/rh:accession`
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	produces	ADP `CHEBI:456216`	RHEA:18634 Source assertion: Rhea lists CHEBI:456216 on the products side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:products; rh:contains/rh:compound/rh:accession`
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	produces	carbamoyl phosphate `CHEBI:58228`	RHEA:18634 Source assertion: Rhea lists CHEBI:58228 on the products side of RHEA:18634 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/18634']/rh:products; rh:contains/rh:compound/rh:accession`
N-acetylglutamate synthase `EC:2.3.1.1`	catalyzes	N-acetylglutamate synthase reaction `RHEA:24293`	RHEA:24292 Source assertion: Rhea associates EC:2.3.1.1 with the reaction family containing RHEA:24293. Source location `rh:ec`
acetylglutamate kinase `EC:2.7.2.8`	catalyzes	N-acetylglutamate kinase reaction `RHEA:14630`	RHEA:14629 Source assertion: Rhea associates EC:2.7.2.8 with the reaction family containing RHEA:14630. Source location `rh:ec`
N-acetyl-gamma-glutamyl-phosphate reductase `EC:1.2.1.38`	catalyzes	N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	RHEA:21588 Source assertion: Rhea associates EC:1.2.1.38 with the reaction family containing RHEA:21590. Source location `rh:ec`
acetylornithine aminotransferase `EC:2.6.1.11`	catalyzes	acetylornithine aminotransferase reaction `RHEA:18051`	RHEA:18049 Source assertion: Rhea associates EC:2.6.1.11 with the reaction family containing RHEA:18051. Source location `rh:ec`
acetylornithine deacetylase `EC:3.5.1.16`	catalyzes	acetylornithine deacetylase reaction `RHEA:15942`	RHEA:15941 Source assertion: Rhea associates EC:3.5.1.16 with the reaction family containing RHEA:15942. Source location `rh:ec`
ornithine carbamoyltransferase `EC:2.1.3.3`	catalyzes	ornithine carbamoyltransferase reaction `RHEA:19514`	RHEA:19513 Source assertion: Rhea associates EC:2.1.3.3 with the reaction family containing RHEA:19514. Source location `rh:ec`
argininosuccinate synthase `EC:6.3.4.5`	catalyzes	argininosuccinate synthase reaction `RHEA:10933`	RHEA:10932 Source assertion: Rhea associates EC:6.3.4.5 with the reaction family containing RHEA:10933. Source location `rh:ec`
argininosuccinate lyase `EC:4.3.2.1`	catalyzes	argininosuccinate lyase reaction `RHEA:24021`	RHEA:24020 Source assertion: Rhea associates EC:4.3.2.1 with the reaction family containing RHEA:24021. Source location `rh:ec`
carbamoyl-phosphate synthase (glutamine-hydrolyzing) `EC:6.3.5.5`	catalyzes	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	RHEA:18633 Source assertion: Rhea associates EC:6.3.5.5 with the reaction family containing RHEA:18634. Source location `rh:ec`
argininosuccinate synthase reaction `RHEA:10933`	precedes	argininosuccinate lyase reaction `RHEA:24021`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:10933 before RHEA:24021 in this pathway. Shared intermediate: CHEBI:57472. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
N-acetylglutamate kinase reaction `RHEA:14630`	precedes	N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:14630 before RHEA:21590 in this pathway. Shared intermediate: CHEBI:57936. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
acetylornithine deacetylase reaction `RHEA:15942`	precedes	ornithine carbamoyltransferase reaction `RHEA:19514`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:15942 before RHEA:19514 in this pathway. Shared intermediate: CHEBI:46911. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
acetylornithine aminotransferase reaction `RHEA:18051`	precedes	acetylornithine deacetylase reaction `RHEA:15942`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:18051 before RHEA:15942 in this pathway. Shared intermediate: CHEBI:57805. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	precedes	ornithine carbamoyltransferase reaction `RHEA:19514`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:18634 before RHEA:19514 in this pathway. Shared intermediate: CHEBI:58228. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
ornithine carbamoyltransferase reaction `RHEA:19514`	precedes	argininosuccinate synthase reaction `RHEA:10933`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:19514 before RHEA:10933 in this pathway. Shared intermediate: CHEBI:57743. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	precedes	acetylornithine aminotransferase reaction `RHEA:18051`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:21590 before RHEA:18051 in this pathway. Shared intermediate: CHEBI:29123. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
N-acetylglutamate synthase reaction `RHEA:24293`	precedes	N-acetylglutamate kinase reaction `RHEA:14630`	MetaCyc:ARGSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:24293 before RHEA:14630 in this pathway. Shared intermediate: CHEBI:44337. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
Carbamoyl phosphate synthase large chain `UniProtKB:P00968`	enables	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	UniProtKB:P00968 Source assertion: UniProt annotates UniProtKB:P00968 with catalytic activity for the reaction family of RHEA:18634. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Carbamoyl phosphate synthase large chain `UniProtKB:P00968`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P00968 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P00968 (evidence: ECO:0000255). Binds 4 Mg(2+) or Mn(2+) ions per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Carbamoyl phosphate synthase large chain `UniProtKB:P00968`	has_cofactor	manganese(2+) `CHEBI:29035`	UniProtKB:P00968 Source assertion: UniProt lists CHEBI:29035 as a cofactor of UniProtKB:P00968 (evidence: ECO:0000255, ECO:0000269). Binds 4 Mg(2+) or Mn(2+) ions per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Ornithine carbamoyltransferase subunit I `UniProtKB:P04391`	enables	ornithine carbamoyltransferase reaction `RHEA:19514`	UniProtKB:P04391 Source assertion: UniProt annotates UniProtKB:P04391 with catalytic activity for the reaction family of RHEA:19514. Annotation evidence: ECO:0000305; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Ornithine carbamoyltransferase subunit I `UniProtKB:P04391`	located_in	cytoplasm `GO:0005737`	UniProtKB:P04391 Source assertion: UniProt locates UniProtKB:P04391 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`
Ornithine carbamoyltransferase subunit F `UniProtKB:P06960`	enables	ornithine carbamoyltransferase reaction `RHEA:19514`	UniProtKB:P06960 Source assertion: UniProt annotates UniProtKB:P06960 with catalytic activity for the reaction family of RHEA:19514. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Ornithine carbamoyltransferase subunit F `UniProtKB:P06960`	located_in	cytoplasm `GO:0005737`	UniProtKB:P06960 Source assertion: UniProt locates UniProtKB:P06960 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`
Amino-acid acetyltransferase `UniProtKB:P0A6C5`	enables	N-acetylglutamate synthase reaction `RHEA:24293`	UniProtKB:P0A6C5 Source assertion: UniProt annotates UniProtKB:P0A6C5 with catalytic activity for the reaction family of RHEA:24293. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
L-arginine `CHEBI:32682`	inhibits	Amino-acid acetyltransferase `UniProtKB:P0A6C5`	UniProtKB:P0A6C5 Source assertion: UniProt activity-regulation annotation: Feedback inhibition by L-arginine Source location `comments[commentType='ACTIVITY REGULATION'].texts`
Amino-acid acetyltransferase `UniProtKB:P0A6C5`	located_in	cytoplasm `GO:0005737`	UniProtKB:P0A6C5 Source assertion: UniProt locates UniProtKB:P0A6C5 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`
Acetylglutamate kinase `UniProtKB:P0A6C8`	enables	N-acetylglutamate kinase reaction `RHEA:14630`	UniProtKB:P0A6C8 Source assertion: UniProt annotates UniProtKB:P0A6C8 with catalytic activity for the reaction family of RHEA:14630. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Acetylglutamate kinase `UniProtKB:P0A6C8`	located_in	cytoplasm `GO:0005737`	UniProtKB:P0A6C8 Source assertion: UniProt locates UniProtKB:P0A6C8 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`
Argininosuccinate synthase `UniProtKB:P0A6E4`	enables	argininosuccinate synthase reaction `RHEA:10933`	UniProtKB:P0A6E4 Source assertion: UniProt annotates UniProtKB:P0A6E4 with catalytic activity for the reaction family of RHEA:10933. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Argininosuccinate synthase `UniProtKB:P0A6E4`	located_in	cytoplasm `GO:0005737`	UniProtKB:P0A6E4 Source assertion: UniProt locates UniProtKB:P0A6E4 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`
Carbamoyl phosphate synthase small chain `UniProtKB:P0A6F1`	enables	hydrogencarbonate + L-glutamine + 2 ATP + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) `RHEA:18634`	UniProtKB:P0A6F1 Source assertion: UniProt annotates UniProtKB:P0A6F1 with catalytic activity for the reaction family of RHEA:18634. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
N-acetyl-gamma-glutamyl-phosphate reductase `UniProtKB:P11446`	enables	N-acetylglutamyl-phosphate reductase reaction `RHEA:21590`	UniProtKB:P11446 Source assertion: UniProt annotates UniProtKB:P11446 with catalytic activity for the reaction family of RHEA:21590. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
N-acetyl-gamma-glutamyl-phosphate reductase `UniProtKB:P11446`	located_in	cytoplasm `GO:0005737`	UniProtKB:P11446 Source assertion: UniProt locates UniProtKB:P11446 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`
Argininosuccinate lyase `UniProtKB:P11447`	enables	argininosuccinate lyase reaction `RHEA:24021`	UniProtKB:P11447 Source assertion: UniProt annotates UniProtKB:P11447 with catalytic activity for the reaction family of RHEA:24021. Annotation evidence: ECO:0000255; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Argininosuccinate lyase `UniProtKB:P11447`	located_in	cytoplasm `GO:0005737`	UniProtKB:P11447 Source assertion: UniProt locates UniProtKB:P11447 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`
Acetylornithine/succinyldiaminopimelate aminotransferase `UniProtKB:P18335`	enables	acetylornithine aminotransferase reaction `RHEA:18051`	UniProtKB:P18335 Source assertion: UniProt annotates UniProtKB:P18335 with catalytic activity for the reaction family of RHEA:18051. Annotation evidence: ECO:0000255, ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Acetylornithine/succinyldiaminopimelate aminotransferase `UniProtKB:P18335`	located_in	cytoplasm `GO:0005737`	UniProtKB:P18335 Source assertion: UniProt locates UniProtKB:P18335 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`
Acetylornithine/succinyldiaminopimelate aminotransferase `UniProtKB:P18335`	has_cofactor	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P18335 Source assertion: UniProt lists CHEBI:597326 as a cofactor of UniProtKB:P18335 (evidence: ECO:0000255, ECO:0000305). Binds 1 pyridoxal phosphate per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Acetylornithine deacetylase `UniProtKB:P23908`	enables	acetylornithine deacetylase reaction `RHEA:15942`	UniProtKB:P23908 Source assertion: UniProt annotates UniProtKB:P23908 with catalytic activity for the reaction family of RHEA:15942. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Acetylornithine deacetylase `UniProtKB:P23908`	located_in	cytoplasm `GO:0005737`	UniProtKB:P23908 Source assertion: UniProt locates UniProtKB:P23908 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`
Acetylornithine deacetylase `UniProtKB:P23908`	has_cofactor	zinc(2+) `CHEBI:29105`	UniProtKB:P23908 Source assertion: UniProt lists CHEBI:29105 as a cofactor of UniProtKB:P23908 (evidence: ECO:0000255, ECO:0000269). Binds 2 Zn(2+) or Co(2+) ions per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Acetylornithine deacetylase `UniProtKB:P23908`	has_cofactor	cobalt(2+) `CHEBI:48828`	UniProtKB:P23908 Source assertion: UniProt lists CHEBI:48828 as a cofactor of UniProtKB:P23908 (evidence: ECO:0000255, ECO:0000269). Binds 2 Zn(2+) or Co(2+) ions per subunit. Source location `comments[commentType='COFACTOR'].cofactors and note`
Acetylornithine deacetylase `UniProtKB:P23908`	has_cofactor	glutathionate(1-) `CHEBI:57925`	UniProtKB:P23908 Source assertion: UniProt lists CHEBI:57925 as a cofactor of UniProtKB:P23908 (evidence: ECO:0000255). Source location `comments[commentType='COFACTOR'].cofactors and note`

References

MetaCyc:ARGSYN-PWY MetaCyc L-arginine biosynthesis I pathway (source version: 22.5)
RHEA:24292 Rhea N-acetylglutamate synthase reaction (source version: 139)
RHEA:24293 Rhea N-acetyl-L-glutamate-forming direction (source version: 139)
RHEA:14629 Rhea N-acetylglutamate kinase reaction (source version: 139)
RHEA:14630 Rhea N-acetylglutamyl 5-phosphate-forming direction (source version: 139)
RHEA:21588 Rhea N-acetylglutamyl-phosphate reductase reaction (source version: 139)
RHEA:21590 Rhea N-acetylglutamate 5-semialdehyde-forming direction (source version: 139)
RHEA:18049 Rhea acetylornithine aminotransferase reaction (source version: 139)
RHEA:18051 Rhea N(2)-acetyl-L-ornithine-forming direction (source version: 139)
RHEA:15941 Rhea acetylornithine deacetylase reaction (source version: 139)
RHEA:15942 Rhea L-ornithine-forming direction (source version: 139)
RHEA:19513 Rhea ornithine carbamoyltransferase reaction (source version: 139)
RHEA:19514 Rhea L-citrulline-forming direction (source version: 139)
RHEA:10932 Rhea argininosuccinate synthase reaction (source version: 139)
RHEA:10933 Rhea argininosuccinate-forming direction (source version: 139)
RHEA:24020 Rhea argininosuccinate lyase reaction (source version: 139)
RHEA:24021 Rhea L-arginine-forming direction (source version: 139)
RHEA:18634 RHEA:18634 authority record (source version: 139)
RHEA:18633 RHEA:18633 authority record (source version: 139)
UniProtKB:P00968 UniProtKB:P00968 authority record (source version: 2026_03)
UniProtKB:P04391 UniProtKB:P04391 authority record (source version: 2026_03)
UniProtKB:P06960 UniProtKB:P06960 authority record (source version: 2026_03)
UniProtKB:P0A6C5 UniProtKB:P0A6C5 authority record (source version: 2026_03)
UniProtKB:P0A6C8 UniProtKB:P0A6C8 authority record (source version: 2026_03)
UniProtKB:P0A6E4 UniProtKB:P0A6E4 authority record (source version: 2026_03)
UniProtKB:P0A6F1 UniProtKB:P0A6F1 authority record (source version: 2026_03)
UniProtKB:P11446 UniProtKB:P11446 authority record (source version: 2026_03)
UniProtKB:P11447 UniProtKB:P11447 authority record (source version: 2026_03)
UniProtKB:P18335 UniProtKB:P18335 authority record (source version: 2026_03)
UniProtKB:P23908 UniProtKB:P23908 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 8 to 9; 0 directed-ID corrections; 11 protein annotations, 6 cofactor annotations and 9 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. Added native pathway reactions: RHEA:18634.
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