Urea cycle and associated pathways (WP4595)

The urea cycle converts toxic nitrogenous compounds to excretable urea in five biochemical reactions. It is also the source for endogenous arginine, ornithine and citrulline production. The process mainly takes place in the liver, partly in the mitochondria and partly in the cytoplasm of the hepatocytes. There are several pathways associated with the urea cycle and with the associated disorders, parts of these pathways are also pictured here. Because there is no alternative way to convert toxic nitrogenous compounds, defects in the enzymes or transporters can lead to several diseases (diseases highlighted in pink). The diseases are characterised by hyperammonemia, respiratory alkalosis and encephalopathy and the severity of the disease depends on the severity of the defect and the place of the defect in the cycle. Severe forms usually have an onset in infancy, while mild forms can also present in adulthood. This pathway was inspired by Chapter 4 of the book of Blau (ISBN 3642403360 (978-3642403361)). For the Urea cycle without additional pathways see: WP4571
last edited


IreneHemel, DeSl, Fehrhart, and Egonw

Cited In


Homo sapiens


Inborn Errors of Metabolism (IEM) Pathways Rare Diseases


Pathway Ontology: disease pathway inborn error of urea cycle pathway urea cycle pathway

Disease Ontology: ornithine carbamoyltransferase deficiency urea cycle disorder argininosuccinic aciduria citrullinemia carbamoyl phosphate synthetase I deficiency disease hyperargininemia

Cell Type Ontology: hepatocyte


Label Type Compact Identifier
ARG1 Protein uniprot:P05089
GLS2 Protein uniprot:Q9UI32
P5CS Protein uniprot:P30038
a-Ketoglutarate Metabolite chebi:16810
Citrulline Metabolite chebi:57743
1-Pyrroline-5-carboxylate Metabolite chebi:17388
Citrin(SLC25A13) Protein uniprot:Q9UJS0
Aspartate Metabolite chebi:29991
ASS1 Protein uniprot:P00966
Acetyl-CoA Metabolite chebi:57288
L-Glutamatey-semialdehyde Metabolite chebi:58066
ASL Protein uniprot:P04424
GDH Protein uniprot:P00367
Pyrimidine metabolismand diseases Pathway wikipathways:WP4225
Oxalacetate Metabolite chebi:16452
LDH Protein uniprot:P07195
ALT Protein uniprot:P24298
Argininosuccinate Metabolite chebi:57472
Ornithine Metabolite chebi:46911
NAGS Protein uniprot:Q8N159
Urea Metabolite chebi:16199
Proline Metabolite chebi:60039
Glutamate Metabolite chebi:29985
Carbamoyl-phosphate Metabolite chebi:58228
MDH Protein uniprot:P40925
Fumarate Metabolite chebi:29806
NH4+ Metabolite chebi:28938
Aspartate metabolism Pathway wikipathways:WP106
MDH2 Protein uniprot:P40926
N-acetylglutamate Metabolite chebi:44337
OTC Protein uniprot:P00480
Pyruvate Metabolite chebi:15361
Lactate Metabolite chebi:16651
OAT Protein uniprot:P04181
SLC25A12 Protein uniprot:O75746
Glutamine Metabolite chebi:58359
AST2 Protein uniprot:P00505
Alanine Metabolite chebi:57972
Malate Metabolite chebi:15589
FUM Protein uniprot:P07954
P5CR Protein uniprot:P32322
HCO3- Metabolite chebi:17544
CPS1 Protein uniprot:P31327
Aspartate Metabolite chebi:29991
Arginine Metabolite chebi:32682
Ornithine Metabolite chebi:46911
ORNT1 Protein uniprot:Q9Y619
Citrulline Metabolite chebi:57743
Oxalacetate Metabolite chebi:16452
Glutamate Metabolite chebi:29985
a-Ketoglutarate Metabolite chebi:16810
AST Protein uniprot:P17174
Pyrimidine metabolismand diseases Pathway wikipathways:WP4225
Orotate Metabolite chebi:30839
OMP Metabolite chebi:57538
Uridine Metabolite chebi:16704
UMP Metabolite chebi:57865
Uracil Metabolite chebi:17568
Orotidine Metabolite chebi:25722
Carbamoyl-phosphate Metabolite chebi:58228
NH4+ Metabolite chebi:28938
Nitric oxide Metabolite chebi:16480
iNOS Protein uniprot:P35228
Urea Cycle Pathway wikipathways:WP4571
Malate Metabolite chebi:15589
Oxalacetate Metabolite chebi:16452
Glutamate Metabolite chebi:29985
nNOS Protein uniprot:P29475
eNOS Protein uniprot:P29474


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