Urea cycle and metabolism of amino groups (WP497)

The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea ((NH2)2CO) from ammonia (NH3). This cycle occurs in ureotelic organisms. The urea cycle converts highly toxic ammonia to urea for excretion. This cycle was the first metabolic cycle to be discovered (Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the TCA cycle. The urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys. Amino acid catabolism results in waste ammonia. All animals need a way to excrete this product. Most aquatic organisms, or ammonotelic organisms, excrete ammonia without converting it. Ammonia is toxic, but upon excretion from aquatic species, it is diluted by the water outside the organism. Organisms that cannot easily and safely remove nitrogen as ammonia convert it to a less toxic substance such as urea or uric acid. The urea cycle mainly occurs in the liver. The urea produced by the liver is then released into the bloodstream where it travels to the kidneys and is ultimately excreted in urine. In species including birds and most insects, the ammonia is converted into uric acid or its urate salt, which is excreted in solid form. Source description: [https://en.wikipedia.org/wiki/Urea_cycle Wikipedia] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP497 CPTAC Assay Portal].
last edited


L.M.Ferrante, MaintBot, Thomas, Khanspers, AdrienDefay, Mkutmon, Egonw, DeSl, IreneHemel, and Finterly

Cited In


Homo sapiens



Pathway Ontology: urea cycle pathway


Label Type Compact Identifier
GAMT Protein uniprot:Q14353
SARDH Protein uniprot:Q9UL12
L-Glutamate Metabolite cas:56-86-0
CKB Protein uniprot:P12277 Protein eccode:
L-Glutamate 5-semialdehyde Metabolite kegg.compound:C01165
Phosphoguanidinoacetate Metabolite kegg.compound:C03166
ODC1 Protein uniprot:P11926
L-Aspartate Metabolite kegg.compound:C00049
NH3 Metabolite kegg.compound:C00014
CPS1 Protein uniprot:P31327 Protein eccode: Protein eccode:
CKM Protein uniprot:P06732
SRM Protein uniprot:P19623 Protein eccode:
PYCRL Protein uniprot:Q53H96
Urea Metabolite cas:57-13-6
Putrescine Metabolite cas:110-60-1
L-Ornithine Metabolite cas:70-26-8
Urea-1-carboxylate Metabolite kegg.compound:C01010
N-(L-Arginino)succinate Metabolite kegg.compound:C03406
Amino acid metabolism Pathway None
Arginine metabolism Pathway None
GLUD1 Protein uniprot:P00367
SMS Protein uniprot:P52788 Protein eccode: Protein eccode:
Proline metabolism Pathway None Protein eccode: Protein eccode:
Creatine Metabolite cas:57-00-1
L-Proline Metabolite cas:147-85-3
ARG1 Protein uniprot:P05089
L-glutamyl Metabolite chebi:29972
Glutamate metabolism Pathway None
L-Citrulline Metabolite cas:372-75-8
D-Arginine and D-Ornithine metabolism Pathway None
ARG2 Protein uniprot:P78540
Arginine Metabolite cas:74-79-3
OAT Protein uniprot:P04181
Guanidinoacetate Metabolite kegg.compound:C00581
ALDH18A1 Protein uniprot:P54886
GATM Protein uniprot:P50440
N2-Acetyl-L-ornithine Metabolite kegg.compound:C00437
Alanine and aspartate metabolism Pathway wikipathways:WP106
SMS Protein uniprot:P52788
Formaldehyde Metabolite cas:50-00-0 Protein eccode:
Sarcosine Metabolite cas:107-97-1
ASS Protein uniprot:P00966
Spermidine Metabolite cas:124-20-9
PYCR1 Protein uniprot:P32322
ASL Protein uniprot:P04424
N-Acetyl-L-glutamate Metabolite kegg.compound:C00624
N-Acetyl-L-glutamate Metabolite kegg.compound:C00624
Citrate cycle (TCA cycle) Pathway wikipathways:WP78
NAGS Protein uniprot:Q8N159
OTC Protein uniprot:P00480 Protein eccode:
Pyrimidine metabolism Pathway None Protein eccode: Protein eccode: GeneProduct eccode:
Spermine Metabolite cas:71-44-3
Creatinine Metabolite cas:60-27-5
ALDH18A1 Protein uniprot:P54886
Carbamoyl Metabolite kegg.compound:C00169 Protein eccode: Protein eccode:
N-Methylhydantoin Metabolite kegg.compound:C02565 Protein eccode:
Nitrogen metabolism Pathway None
Formate Metabolite kegg.compound:C00058
creatine-P Metabolite cas:67-07-2
ACY1 Protein uniprot:Q03154
N-Acetyl-glutamate Metabolite kegg.compound:C00624
Purine metabolism Pathway None
N-Carbamoylsarcosine Metabolite kegg.compound:C01043
CO2 Metabolite kegg.compound:C00011
(S)-1-Pyrroline-5-carboxylate Metabolite kegg.compound:C03912
Fumarate Metabolite kegg.compound:C00122


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