ornithine transcarbamoylase

オルニチン回路での反応

• オルニチン + カルバモイルリン酸　－ornithine transcarbamoylase→　シトルリン +Pi

WordNet

1. an amino acid that does not occur in proteins but is important in the formation of urea

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/06/28 10:31:23」(JST)

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OTC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1OTH, 1C9Y, 1EP9, 1FVO
Identifiers
Aliases	OTC, OCTD, ornithine carbamoyltransferase
External IDs	OMIM: 300461 MGI: 97448 HomoloGene: 446 GeneCards: 5009
Gene ontology Molecular function • amino acid binding • transferase activity • carboxyl- or carbamoyltransferase activity • phosphate ion binding • phospholipid binding • ornithine carbamoyltransferase activity Cellular component • cytoplasm • mitochondrial inner membrane • mitochondrial matrix • mitochondrion Biological process • response to zinc ion • cellular amino acid biosynthetic process • ornithine catabolic process • response to drug • midgut development • polyamine metabolic process • cellular amino acid metabolic process • cellular nitrogen compound metabolic process • response to nutrient levels • response to biotin • anion homeostasis • liver development • arginine biosynthetic process • response to insulin • small molecule metabolic process • ammonia homeostasis • ornithine metabolic process • arginine biosynthetic process via ornithine • protein homotrimerization • urea cycle • citrulline biosynthetic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5009	18416
Ensembl	ENSG00000036473	ENSMUSG00000031173
UniProt	P00480	P11725
RefSeq (mRNA)	NM_000531	NM_008769
RefSeq (protein)	NP_000522.3	NP_032795.1
Location (UCSC)	Chr X: 38.35 – 38.42 Mb	Chr X: 10.25 – 10.32 Mb
PubMed search	[1]	[2]
Wikidata
View/Edit Human		View/Edit Mouse

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 (P_i). 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.

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.

Genomics

The gene is located on the short arm of chromosome X (Xp21.1). The gene is located in the Watson (plus) strand and is 68,968 bases in length. The encoded protein is 354 amino acids long with a predicted molecular weight of 39.935 kiloDaltons. The protein is located in the mitochondrial matrix.

Function

The reaction mechanism of OTC.

The side-chain amino group of Orn attacks the carbonyl carbon of CP nucleophilically, left, to form a tetrahedral transition state, middle. Charge rearrangement releases Cit and P_i, right.

Deficiency

Main article: Ornithine transcarbamylase deficiency

OTC monomer

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).

Because newborns are usually discharged from the hospital within 1–2 days after birth, the symptoms of a urea cycle disorder are often not seen until the child is at home and may not be recognized in a timely manner by the family and primary-care physician. The typical initial symptoms of a child with hyperammonemia are non-specific: failure to feed, loss of thermoregulation with a low core temperature, and somnolence. Symptoms progress from somnolence to lethargy and coma. Abnormal posturing and encephalopathy are often related to the degree of central nervous system swelling and pressure upon the brainstem. About 50% of neonates with severe hyperammonemia have seizures.

Hyperventilation, secondary to cerebral edema, is a common early finding in a hyperammonemic attack, which causes a respiratory alkalosis. Hypoventilation and respiratory arrest follow, as pressure increases on the brainstem. In milder (or partial) urea cycle enzyme deficiencies, ammonia accumulation may be triggered by illness or stress at almost any time of life, resulting in multiple mild elevations of plasma ammonia concentration [Bourrier et al. 1988]. The hyperammonemia is less severe and the symptoms more subtle. In patients with partial enzyme deficiencies, the first recognized clinical episode may be delayed for months or years. One in 70000 adults has an ornithine transcarbamylase deficiency.

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. Biotin also plays an important role in the functioning of the OTC enzyme and has been shown to reduce ammonia intoxication in animal experiments.

References

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. doi:10.1002/(SICI)1096-8628(19970905)71:4<378::AID-AJMG2>3.0.CO;2-Q. 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. doi:10.1097/00075197-199807000-00004. 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. PMC 1016021. 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. doi:10.1203/00006450-199211000-00024. PMID 1480464. 
• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. 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. doi:10.1016/0885-4505(92)90033-U. PMID 1627356. 
• Grompe M, Caskey CT, Fenwick RG (1991). "Improved molecular diagnostics for ornithine transcarbamylase deficiency". Am. J. Hum. Genet. 48 (2): 212–22. PMC 1683033. 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. doi:10.1007/bf00206063. 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. doi:10.1136/jmg.28.12.871. PMC 1017166. 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. PMC 1683104. 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. doi:10.1007/BF01213087. 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. doi:10.1111/j.1399-0004.1990.tb03565.x. 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. doi:10.1016/0888-7543(90)90537-5. 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. doi:10.1073/pnas.86.15.5888. PMC 297736. 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. doi:10.1172/JCI114360. PMC 304053. 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. PMC 1683378. PMID 2741942. 
• Summar ML, Tuchman M (29 April 2003). "Urea Cycle Disorders Overview" (PDF). University of Washington, Seattle. 

External links

• GeneReviews/NCBI/NIH/UW entry on Urea Cycle Disorders Overview

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 成人における肝性脳症：治療 hepatic encephalopathy in adults treatment
• 2. 尿素サイクル障害：臨床的特徴および診断 urea cycle disorders clinical features and diagnosis
• 3. 尿素サイクル障害：管理 urea cycle disorders management
• 4. 先天性代謝異常：個々の障害の発見 inborn errors of metabolism identifying the specific disorder
• 5. 遺伝性運動失調の概要 overview of the hereditary ataxias

English Journal

• Implication of ornithine acetyltransferase activity on l-ornithine production in Corynebacterium glutamicum.

• Hao N1, Mu J1, Hu N1, Xu S1, Shen P1, Yan M1, Li Y1, Xu L1.
• Biotechnology and applied biochemistry.Biotechnol Appl Biochem.2016 Feb;63(1):15-21. doi: 10.1002/bab.1353. Epub 2015 Aug 13.
• l-Ornithine is an intermediate of the l-arginine biosynthetic pathway in Corynebacterium glutamicum. The effect of ornithine acetyltransferase (OATase; ArgJ) on l-ornithine production was investigated, and C. glutamicum 1006 was engineered to overproduce l-ornithine as a major product by inactivatin
• PMID 25630515

• Ornithine transcarbamylase deficiency of a male newborn with fatal outcome.

• Hartung B1, Temme O2, Neuen-Jacob E3, Ritz-Timme S2, Hinderhofer K4, Daldrup T2.
• International journal of legal medicine.Int J Legal Med.2016 Jan 11. [Epub ahead of print]
• Ornithine transcarbamylase deficiency (OTCD) is the most common malfunction of ureagenesis. The case of a male newborn who died at the age of 2 days for clinically unclear reasons is presented. The post-mortem routine and esoteric testing methods that finally led to the diagnosis of a fatal case of
• PMID 26753873

• In vivo monitoring of urea cycle activity with (13)C-acetate as a tracer of ureagenesis.

• Opladen T1, Lindner M2, Das AM3, Marquardt T4, Khan A5, Emre SH6, Burton BK7, Barshop BA8, Böhm T9, Meyburg J10, Zangerl K11, Mayorandan S12, Burgard P13, Dürr UH14, Rosenkranz B15, Rennecke J16, Derbinski J17, Yudkoff M18, Hoffmann GF19.
• Molecular genetics and metabolism.Mol Genet Metab.2016 Jan;117(1):19-26. doi: 10.1016/j.ymgme.2015.11.007. Epub 2015 Nov 14.
• BACKGROUND: The hepatic urea cycle is the main metabolic pathway for detoxification of ammonia. Inborn errors of urea cycle function present with severe hyperammonemia and a high case fatality rate. Long-term prognosis depends on the residual activity of the defective enzyme. A reliable method to es
• PMID 26597322

Japanese Journal

• Requirement for Mesorhizobium loti Ornithine Transcarbamoylase for Successful Symbiosis with Lotus japonicus as Revealed by an Unexpected Long-Range Genome Deletion

• Mishima Elina,Hosokawa Atsuko,Imaizumi-Anraku Haruko [他],SAITO Katsuharu,KAWAGUCHI Masayoshi,SAEKI Kazuhiko
• Plant and cell physiology 49(3), 301-313, 2008-03-01
• NAID 10027329212

• Glycosylation Variant Analysis of Recombinant Human Tissue Plasminogen Activator Produced in Urea-Cycle-Enzyme-Expressing Chinese Hamster Ovary (CHO) Cell Line(BIOCHEMICAL ENGINEERING)

• Kim Hyoung Jin,Kim Hong-Jin
• Journal of bioscience and bioengineering 102(5), 447-451, 2006-11-25
• … Tissue plasminogen activator (tPA) was produced in ornithine transcarbamoylase (OTC) cells by introducing the tPA gene into OTC cells. …
• NAID 110006148696

• Identification of a mammalian 10-kDa heat shock protein, a mitochondrial chaperonin 10 homologue essential for assisted folding of trimeric ornithine transcarbamoylase in vitro

• HARTMAN D. J.
• Proc Natl Acad Sci USA 89, 3394-3398, 1992
• NAID 30016293555

Related Links

• Ornithine transcarbamylase - Wikipedia, the free encyclopedia

Ornithine transcarbamoylase (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 ...

• Ornithine transcarbamylase deficiency - Wikipedia, the free ...

Ornithine transcarbamylase deficiency (OTCD), a common urea cycle disorder, is a rare metabolic disorder, occurring in one out of every 80,000 births. OTCD is a genetic disorder resulting in a mutated and ineffective form of the enzyme ...

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★リンクテーブル★

リンク元	「オルニチン」「オルニチンカルバモイルトランスフェラーゼ」「オルニチントランスカルバモイラーゼ」
拡張検索	「ornithine transcarbamoylase deficiency」
関連記事	「transcarbamoylase」

「オルニチン」

　　[★]

英

ornithine, Orn

同

α,δ-ジアミノ-n-吉草酸 α,δ-diamino-n-valeric acid、2,5-ジアミノ-n-吉草酸 2,5-diamino-n-valeric acid、2,5ジアミノペンタン酸 2,5-diamino pentanoic acid

関

オルニチン回路

• アミノ酸の一種
• 尿素回路でアルギニンから得られる。アルギニンから-C(NH)(NH₃⁺)が取れた形。
• 極性、塩基性

　-CH2-CH2-CH2-NH2
  α  β  γ ＞γアミノ基を有する。即ち、側鎖には炭素が３つ含まれる。＜リジンと比べて炭素が一つ少ない。

オルニチン回路での反応

• アルギニン + H₂O －アルギナーゼ→　オルニチン + 尿素 O=C(NH₂)₂
• オルニチン + カルバモイルリン酸　－ornithine transcarbamoylase→　シトルリン +Pi

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• これはリジン

「オルニチンカルバモイルトランスフェラーゼ」

　　[★]

英

ornithine carbamoyl transferase

同

オルニチントランスカルバミラーゼ ornithine transcarbamoylase

関

オルニチン回路、オルニチントランスカルバミラーゼ欠損症、

• 肝臓のミトコンドリア内に局在する。
• カルバモイルリン酸からオルニチンのδ-アミノ基へのカルバモイル基転移によってシトルリンを生ずる反応を触媒する酵素。

カルバモイルリン酸＋オルニチン－－(オルニチンカルバモイルトランスフェラーゼ)－→シトルリン＋リン酸

「オルニチントランスカルバモイラーゼ」

　　[★]

英

ornithine transcarbamoylase

「ornithine transcarbamoylase deficiency」

　　[★]

オルニチントランスカルバミラーゼ欠損症

「transcarbamoylase」

　　[★]

トランスカルバモイラーゼ