Ornithine transcarbamylase
| Ornithine carbamoyltransferase
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| Human OTC trimer. From PDB 1OTH.
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| Available structures: 1c9y, 1ep9, 1fb5, 1fvo, 1oth
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| Identifiers
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| Symbol(s)
| OTC; OCTD; MGC129967; MGC129968; MGC138856
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| External IDs
| OMIM: 300461 MGI: 97448 Homologene: 446
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| Gene Ontology
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| Molecular Function:
| • ornithine carbamoyltransferase activity
• amino acid binding
• transferase activity
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| Cellular Component:
| • mitochondrion
• mitochondrial inner membrane
• mitochondrial matrix
• ornithine carbamoyltransferase complex
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| Biological Process:
| • urea cycle
• arginine biosynthetic process
• amino acid biosynthetic process
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| RNA expression pattern
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More reference expression data
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| Orthologs
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| Human
| Mouse
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| Entrez
| 5009
| 18416
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| Ensembl
| ENSG00000036473
| ENSMUSG00000031173
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| Uniprot
| P00480
| Q543H3
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| Refseq
| NM_000531 (mRNA)
NP_000522 (protein)
| NM_008769 (mRNA)
NP_032795 (protein)
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| Location
| Chr X: 38.1 - 38.17 Mb
| Chr X: 9.41 - 9.48 Mb
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| Pubmed search
| [1]
| [2]
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Ornithine transcarbamylase (OTC) (also called ornithine carbamoyltransferase) is an enzyme that catalyzes the reaction between carbamoyl phosphate (CP) and ornithine (Orn) to form citrulline (Cit) and phosphate (Pi). In plants and microbes OTC is involved in arginine (Arg) biosynthesis, whereas in mammals it is located in the mitochondria and is part of the urea cycle.
Additional recommended knowledge
Structure
OTC is a trimer. The monomer unit has a CP-binding domain and an amino acid-binding domain. Each of the two discrete substrate-binding domains (SBDs) have an α/β topology with a central β-pleated sheet embedded in flanking α-helices.
The active sites are located at the interface between the protein monomers.
Function
Deficiency
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If a person is deficient in OTC, ammonia levels will build up, and this will cause neurological problems. Levels of the amino acids glutamate and alanine, will be increased (as these are the amino acids that receive nitrogen from others).
Levels of urea cycle intermediates may be decreased, as carbamoyl phosphate cannot replenish the cycle. The carbamoyl phosphate instead goes into the uridine monophosphate synthetic pathway. Here orotic acid (one step of this alternative pathway) levels in the blood are increased.
A potential treatment for the high ammonia levels is to give sodium benzoate, which combines with glycine to produce hippurate, at the same time removing an ammonium group.
References
- a Mechanism of inactivation of ornithine transcarbamoylase by Ndelta -(N'-Sulfodiaminophosphinyl)-L-ornithine, a true transition state analogue? Crystal structure and implications for catalytic mechanism. J Biol Chem. 2000 Jun 30; 275: 20012-9; PubMed Free text
Further reading
- Tuchman M, Plante RJ (1995). "Mutations and polymorphisms in the human ornithine transcarbamylase gene: mutation update addendum.". Hum. Mutat. 5 (4): 293-5. doi:10.1002/humu.1380050404. PMID 7627182.
- Tuchman M (1993). "Mutations and polymorphisms in the human ornithine transcarbamylase gene.". Hum. Mutat. 2 (3): 174-8. doi:10.1002/humu.1380020304. PMID 8364586.
- Matsuda I, Tanase S (1997). "The ornithine transcarbamylase (OTC) gene: mutations in 50 Japanese families with OTC deficiency.". Am. J. Med. Genet. 71 (4): 378-83. PMID 9286441.
- Wakabayashi Y (1999). "Tissue-selective expression of enzymes of arginine synthesis.". Current opinion in clinical nutrition and metabolic care 1 (4): 335-9. PMID 10565370.
- Tuchman M, Jaleel N, Morizono H, et al. (2002). "Mutations and polymorphisms in the human ornithine transcarbamylase gene.". Hum. Mutat. 19 (2): 93-107. doi:10.1002/humu.10035. PMID 11793468.
- Feldmann D, Rozet JM, Pelet A, et al. (1992). "Site specific screening for point mutations in ornithine transcarbamylase deficiency.". J. Med. Genet. 29 (7): 471-5. PMID 1353535.
- Tuchman M, Holzknecht RA, Gueron AB, et al. (1993). "Six new mutations in the ornithine transcarbamylase gene detected by single-strand conformational polymorphism.". Pediatr. Res. 32 (5): 600-4. PMID 1480464.
- Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317-20. PMID 1602151.
- Suess PJ, Tsai MY, Holzknecht RA, et al. (1992). "Screening for gene deletions and known mutations in 13 patients with ornithine transcarbamylase deficiency.". Biochem. Med. Metab. Biol. 47 (3): 250-9. PMID 1627356.
- Grompe M, Caskey CT, Fenwick RG (1991). "Improved molecular diagnostics for ornithine transcarbamylase deficiency.". Am. J. Hum. Genet. 48 (2): 212-22. PMID 1671317.
- Hentzen D, Pelet A, Feldman D, et al. (1992). "Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene.". Hum. Genet. 88 (2): 153-6. PMID 1721894.
- Strautnieks S, Rutland P, Malcolm S (1992). "Arginine 109 to glutamine mutation in a girl with ornithine carbamoyl transferase deficiency.". J. Med. Genet. 28 (12): 871-4. PMID 1757964.
- Carstens RP, Fenton WA, Rosenberg LR (1991). "Identification of RNA splicing errors resulting in human ornithine transcarbamylase deficiency.". Am. J. Hum. Genet. 48 (6): 1105-14. PMID 2035531.
- Hata A, Matsuura T, Setoyama C, et al. (1991). "A novel missense mutation in exon 8 of the ornithine transcarbamylase gene in two unrelated male patients with mild ornithine transcarbamylase deficiency.". Hum. Genet. 87 (1): 28-32. PMID 2037279.
- Legius E, Baten E, Stul M, et al. (1990). "Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion.". Clin. Genet. 38 (2): 155-9. PMID 2208768.
- Finkelstein JE, Francomano CA, Brusilow SW, Traystman MD (1990). "Use of denaturing gradient gel electrophoresis for detection of mutation and prospective diagnosis in late onset ornithine transcarbamylase deficiency.". Genomics 7 (2): 167-72. PMID 2347583.
- Grompe M, Muzny DM, Caskey CT (1989). "Scanning detection of mutations in human ornithine transcarbamoylase by chemical mismatch cleavage.". Proc. Natl. Acad. Sci. U.S.A. 86 (15): 5888-92. PMID 2474822.
- Lee JT, Nussbaum RL (1990). "An arginine to glutamine mutation in residue 109 of human ornithine transcarbamylase completely abolishes enzymatic activity in Cos1 cells.". J. Clin. Invest. 84 (6): 1762-6. PMID 2556444.
- Chu TW, Eftime R, Sztul E, Strauss AW (1989). "Synthetic transit peptides inhibit import and processing of mitochondrial precursor proteins.". J. Biol. Chem. 264 (16): 9552-8. PMID 2722850.
- Hata A, Setoyama C, Shimada K, et al. (1989). "Ornithine transcarbamylase deficiency resulting from a C-to-T substitution in exon 5 of the ornithine transcarbamylase gene.". Am. J. Hum. Genet. 45 (1): 123-7. PMID 2741942.
| Urea cycle enzymes |
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| Main cycle | Carbamoyl phosphate synthase I - Ornithine transcarbamylase - Argininosuccinate synthetase - Argininosuccinate lyase - Arginase |
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| Regulatory/transport | N-Acetylglutamate synthase - Ornithine translocase |
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