Urea cycle and related diseases (WP4571)

Homo sapiens

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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 Weitz

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

hepatocyte

Disease Ontology

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

Pathway Ontology

disease pathway inborn error of urea cycle pathway urea cycle pathway

Participants
Query Drugst.One

Label 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
Aspartate Metabolite chebi:29991 (1-) charge needed for conversion to take place
Arginine Metabolite chebi:32682 (1) charge needed for conversion to take place
Ornithine Metabolite chebi:46911 (1) charge needed for conversion to take place
Citrulline Metabolite chebi:57743 Zwitterion 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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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