Urea cycle and metabolism of amino groups (WP497)

Homo sapiens

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].


Lynn M. Ferrante , Thomas Kelder , Kristina Hanspers , Adrien Defay , Martina Summer-Kutmon , Egon Willighagen , Denise Slenter , Irene Hemel , and Finterly Hu


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Homo sapiens



Pathway Ontology

urea cycle pathway


Label Type Compact URI Comment
L-Glutamate Metabolite cas:56-86-0 L-Glutamate
L-Glutamate 5-semialdehyde Metabolite kegg.compound:C01165 tautomer of (S)-1-Pyrroline-5-carboxylate
Phosphoguanidinoacetate Metabolite kegg.compound:C03166
L-Aspartate Metabolite kegg.compound:C00049
NH3 Metabolite kegg.compound:C00014
Urea Metabolite cas:57-13-6 Urea
Putrescine Metabolite cas:110-60-1 Putrescine
L-Ornithine Metabolite cas:70-26-8 L-Ornithine
Urea-1-carboxylate Metabolite kegg.compound:C01010
N-(L-Arginino)succinate Metabolite kegg.compound:C03406
Creatine Metabolite cas:57-00-1 Creatine
L-Proline Metabolite cas:147-85-3 L-Proline
L-glutamyl Metabolite chebi:29972
L-Citrulline Metabolite cas:372-75-8 L-Citrulline
Arginine Metabolite cas:74-79-3 L-Arginine
Guanidinoacetate Metabolite kegg.compound:C00581
N2-Acetyl-L-ornithine Metabolite kegg.compound:C00437
Formaldehyde Metabolite cas:50-00-0 Formaldehyde
Sarcosine Metabolite cas:107-97-1 Sarcosine
Spermidine Metabolite cas:124-20-9 Spermidine
N-Acetyl-L-glutamate Metabolite kegg.compound:C00624
N-Acetyl-L-glutamate Metabolite kegg.compound:C00624
Spermine Metabolite cas:71-44-3 Spermine
Creatinine Metabolite cas:60-27-5 Creatinine
Carbamoyl Metabolite kegg.compound:C00169
N-Methylhydantoin Metabolite kegg.compound:C02565
Formate Metabolite kegg.compound:C00058
creatine-P Metabolite cas:67-07-2 Phosphocreatine
N-Acetyl-glutamate Metabolite kegg.compound:C00624
N-Carbamoylsarcosine Metabolite kegg.compound:C01043
CO2 Metabolite kegg.compound:C00011
(S)-1-Pyrroline-5-carboxylate Metabolite kegg.compound:C03912 Tautomer of L-glutamate 5-semialdehyde
Fumarate Metabolite kegg.compound:C00122 GeneProduct eccode:
GAMT Protein uniprot:Q14353
SARDH Protein uniprot:Q9UL12
CKB Protein uniprot:P12277 Protein eccode:
ODC1 Protein uniprot:P11926
CPS1 Protein uniprot:P31327 Protein eccode: Protein eccode:
CKM Protein uniprot:P06732
SRM Protein uniprot:P19623 Protein eccode:
PYCRL Protein uniprot:Q53H96
GLUD1 Protein uniprot:P00367
SMS Protein uniprot:P52788 Protein eccode: Protein eccode: Protein eccode: Protein eccode:
ARG1 Protein uniprot:P05089
ARG2 Protein uniprot:P78540
OAT Protein uniprot:P04181
ALDH18A1 Protein uniprot:P54886
GATM Protein uniprot:P50440
SMS Protein uniprot:P52788 Protein eccode:
ASS Protein uniprot:P00966
PYCR1 Protein uniprot:P32322
ASL Protein uniprot:P04424
NAGS Protein uniprot:Q8N159
OTC Protein uniprot:P00480 Protein eccode: Protein eccode: Protein eccode:
ALDH18A1 Protein uniprot:P54886 Protein eccode: Protein eccode: Protein eccode:
ACY1 Protein uniprot:Q03154


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