Urea cycle and related diseases (WP4571)
Homo sapiens
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. 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 is based on: Mew NA, et al. Urea cycle disorders overview (2003) [https://www.ncbi.nlm.nih.gov/books/NBK1217/]
Authors
Irene Hemel , Denise Slenter , Friederike Ehrhart , Egon Willighagen , and Eric WeitzActivity
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Cited In
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Organisms
Homo sapiensCommunities
Annotations
Cell Type Ontology
hepatocyteDisease Ontology
citrullinemia urea cycle disorder carbamoyl phosphate synthetase I deficiency disease ornithine carbamoyltransferase deficiency argininosuccinic aciduria hyperargininemiaPathway Ontology
disease pathway inborn error of urea cycle pathway urea cycle pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
Citrulline | Metabolite | chebi:57743 | Zwitterion needed for conversion to take place |
Aspartate | Metabolite | chebi:29991 | (1-) charge needed for conversion to take place |
Acetyl-CoA | Metabolite | chebi:57288 | (4-) charge needed for conversion to take place |
Argininosuccinate | Metabolite | chebi:57472 | (1-) charge needed for conversion to take place |
Ornithine | Metabolite | chebi:46911 | (1) charge needed for conversion to take place |
Urea | Metabolite | chebi:16199 | |
Glutamate | Metabolite | chebi:29985 | (1-) charge needed for conversion to take place |
Carbamoyl-phosphate | Metabolite | chebi:58228 | (2-) charge needed for conversion to take place |
Fumarate | Metabolite | chebi:29806 | (2-) charge needed for conversion to take place |
NH4+ | Metabolite | chebi:28938 | |
N-acetylglutamate | Metabolite | chebi:44337 | (2-) charge needed for conversion to take place |
Glutamine | Metabolite | chebi:58359 | Zwitterion needed for conversion to take place |
HCO3- | Metabolite | chebi:17544 | |
Arginine | Metabolite | chebi:32682 | (1) charge needed for conversion to take place |
ARG1 | Protein | uniprot:P05089 | |
GLS2 | Protein | uniprot:Q9UI32 | |
ORNT1 | Protein | uniprot:Q9Y619 | |
Citrin | Protein | uniprot:Q9UJS0 | |
ASS1 | Protein | uniprot:P00966 | |
ASL | Protein | uniprot:P04424 | |
NAGS | Protein | uniprot:Q8N159 | |
OTC | Protein | uniprot:P00480 | |
CPS1 | Protein | uniprot:P31327 |
References
- Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, et al. Pediatr Res. 2006 Oct;60(4):423–9. PubMed Europe PMC Scholia
- Arginase Deficiency. Sun A, Crombez EA, Wong D. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2004. PubMed Europe PMC Scholia
- Citrin Deficiency. Saheki T, Song YZ. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2005. PubMed Europe PMC Scholia
- Urea Cycle Disorders Overview. Ah Mew N, Simpson KL, Gropman AL, Lanpher BC, Chapman KA, Summar ML. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2003. PubMed Europe PMC Scholia
- Citrullinemia Type I. Quinonez SC, Lee KN. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2004. PubMed Europe PMC Scholia
- Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylase deficiency. Kido J, Kawasaki T, Mitsubuchi H, Kamohara H, Ohba T, Matsumoto S, et al. World J Hepatol. 2017 Feb 28;9(6):343–8. PubMed Europe PMC Scholia
- Neonatal-onset carbamoyl phosphate synthetase I deficiency: A case report. Yang X, Shi J, Lei H, Xia B, Mu D. Medicine (Baltimore). 2017 Jun;96(26):e7365. PubMed Europe PMC Scholia
- Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer. Baruteau J, Perocheau DP, Hanley J, Lorvellec M, Rocha-Ferreira E, Karda R, et al. Nat Commun. 2018 Aug 29;9(1):3505. PubMed Europe PMC Scholia
- N-Acetylglutamate Synthase Deficiency Due to a Recurrent Sequence Variant in the N-acetylglutamate Synthase Enhancer Region. Williams M, Burlina A, Rubert L, Polo G, Ruijter GJG, van den Born M, et al. Sci Rep. 2018 Oct 18;8(1):15436. PubMed Europe PMC Scholia