| Record Information |
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| Version | 2.0 |
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| Created at | 2005-11-16 15:48:42 UTC |
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| Updated at | 2025-02-11 15:47:15 UTC |
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| NP-MRD ID | NP0000198 |
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| Natural Product DOI | https://doi.org/10.57994/0811 |
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| Secondary Accession Numbers | None |
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| Natural Product Identification |
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| Common Name | Orotic acid |
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| Description | Orotic acid is classified as a pyrimidinemonocarboxylic acid. That is it is a uracil bearing a carboxy substituent at position C-6. It is also classified as a pyrimidinedione and a carboxylic acid. Orotic acid is a minor dietary constituent. Indeed, until it was realized that it could be synthesized by humans, orotic acid was known as vitamin B-13. The richest dietary sources of orotic acid are cow's milk and other dairy products as well as root vegetables such as carrots and beets. Dietary intake probably contributes to a basal rate of orotic acid excretion in urine because fasting decreases excretion by ~50%. However, it is now apparent that most urinary orotic acid is synthesized in the body, where it arises as an intermediate in the pathway for the synthesis of pyrimidine nucleotides. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotate phosphoribosyltransferase and orotidylate decarboxylase activity. The most frequently observed inborn error of pyrimidine nucleotide synthesis is a mutation of the multifunctional protein UMP synthase (UMP synthase deficiency or orotic aciduria). This disorder prevents the conversion of orotic acid to UMP, and thus to other pyrimidines. As a result, plasma orotic acid accumulates to high concentrations, and increased quantities appear in the urine. Indeed, urinary orotic acid is so markedly increased in individuals harboring a mutation in UMP synthase that orotic acid crystals can form in the urine. The urinary concentration of orotic acid in individuals suffering from orotic aciduria can be of the order of millimoles of orotic acid per millimole creatinine. By comparison, the urinary level in unaffected individuals is ~ 1 ¬umol/mmol creatinine (PMID: 17513443 ). Orotic aciduria is characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy and most cases appear to have a good prognosis. When present in sufficiently high levels, orotic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of orotic acid are associated with at least seven inborn errors of metabolism, including argininemia, LPI syndrome (lysinuric protein intolerance), hyperornithinemia-hyperammonemia-homocitrullinuria (HHH), OTC deficiency, citrullinemia type I, purine nucleoside phosphorylase deficiency, and orotic aciduria. Orotic acid is broadly classified as an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures. | Read more...
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| Structure | InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11) |
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| Synonyms | | Value | Source |
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| Orotsaeure | ChEBI | | Uracil-6-carboxylic acid | ChEBI | | Uracil-6-carboxylate | Generator | | Orotate | Generator | | 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylic acid | HMDB | | 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid | HMDB | | 1,2,3,6-Tetrahydro-2,6-dioxopyrimidin-4-carbonsaeure | HMDB | | 2,6-Dihydroxy-4-pyrimidinecarboxylic acid | HMDB | | 2,6-Dihydroxypyrimidine-4-carboxylic acid | HMDB | | 2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acid | HMDB | | 2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid | HMDB | | 6-Carboxy-2,4-dihydroxypyrimidine | HMDB | | 6-Carboxyuracil | HMDB | | 6-Uracilcarboxylic acid | HMDB | | Acide orotique | HMDB | | Acido orotico | HMDB | | Acidum oroticum | HMDB | | Animal galactose factor | HMDB | | Lactinium | HMDB | | Molkensaeure | HMDB | | ORO | HMDB | | Orodin | HMDB | | Oropur | HMDB | | Orotonin | HMDB | | Orotonsan | HMDB | | Orotsaure | HMDB | | Oroturic | HMDB | | Orotyl | HMDB | | Uracil-6-carbosaeure | HMDB | | Vitamin b13 | HMDB | | Whey factor | HMDB | | Zinc orotate | HMDB | | Orotate, zinc | HMDB | | Acid, orotic | HMDB | | Orotate, potassium | HMDB | | Potassium orotate | HMDB | | Orotate, sodium | HMDB | | Sodium orotate | HMDB |
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| Chemical Formula | C5H4N2O4 |
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| Average Mass | 156.0963 Da |
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| Monoisotopic Mass | 156.01711 Da |
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| IUPAC Name | 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid |
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| Traditional Name | orotic acid |
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| CAS Registry Number | 65-86-1 |
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| SMILES | OC(=O)C1=CC(=O)NC(=O)N1 |
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| InChI Identifier | InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11) |
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| InChI Key | PXQPEWDEAKTCGB-UHFFFAOYSA-N |
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| Experimental Spectra |
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| | Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
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| 1D NMR | 1H NMR Spectrum (1D, 600 MHz, CD3OD, experimental) | bgnzk@missouri.edu | Not Available | Not Available | 2023-08-14 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, CD3OD, experimental) | bgnzk@missouri.edu | Not Available | Not Available | 2023-08-14 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum | | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum |
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| Predicted Spectra |
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| Not Available |
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| Chemical Shift Submissions |
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| | Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
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| 1D NMR | 1H NMR Spectrum (1D, 600.133705802, CD3OD, simulated) | bgnzk@missouri.edu | Sumner Lab, MU Metabolomics Center, University of Missouri, Columbia. MO, USA | Dr. Bharat Goel | 2024-05-14 | View Spectrum |
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| Species |
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| Species of Origin | | Show more...
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| Species Where Detected | |
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| Chemical Taxonomy |
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| Description | Belongs to the class of organic compounds known as pyrimidinecarboxylic acids. These are pyrimidines with a structure containing a carboxyl group attached to the pyrimidine ring. |
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| Kingdom | Organic compounds |
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| Super Class | Organoheterocyclic compounds |
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| Class | Diazines |
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| Sub Class | Pyrimidines and pyrimidine derivatives |
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| Direct Parent | Pyrimidinecarboxylic acids |
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| Alternative Parents | |
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| Substituents | - Pyrimidine-6-carboxylic acid
- Hydropyrimidine carboxylic acid derivative
- Pyrimidone
- Hydropyrimidine
- Heteroaromatic compound
- Vinylogous amide
- Urea
- Lactam
- Azacycle
- Monocarboxylic acid or derivatives
- Carboxylic acid
- Carboxylic acid derivative
- Organic nitrogen compound
- Organic oxygen compound
- Organopnictogen compound
- Organic oxide
- Hydrocarbon derivative
- Organooxygen compound
- Organonitrogen compound
- Aromatic heteromonocyclic compound
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| Molecular Framework | Aromatic heteromonocyclic compounds |
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| External Descriptors | |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | 345.5 °C | Not Available | | Boiling Point | 656.00 to 657.00 °C. @ 760.00 mm Hg (est) | The Good Scents Company Information System | | Water Solubility | 1.82 mg/mL at 18 °C | Not Available | | LogP | -0.83 | Sangster, J. (1993). LOGKOW- a Databank of Evaluated Octanol-Water Partition Coefficients. Sangster Research Laboratories, Montreal. |
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| Predicted Properties | |
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| External Links |
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| HMDB ID | HMDB0000226 |
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| DrugBank ID | DB02262 |
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| Phenol Explorer Compound ID | Not Available |
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| FoodDB ID | FDB031072 |
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| KNApSAcK ID | C00019689 |
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| Chemspider ID | 942 |
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| KEGG Compound ID | C00295 |
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| BioCyc ID | OROTATE |
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| BiGG ID | 34527 |
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| Wikipedia Link | Orotic_acid |
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| METLIN ID | 318 |
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| PubChem Compound | 967 |
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| PDB ID | Not Available |
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| ChEBI ID | 16742 |
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| Good Scents ID | rw1099361 |
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| References |
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| General References | - Zieve L: Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 1986;5(2):167-76. [PubMed:3088083 ]
- Visek WJ: Ammonia: its effects on biological systems, metabolic hormones, and reproduction. J Dairy Sci. 1984 Mar;67(3):481-98. [PubMed:6371080 ]
- Arranz JA, Riudor E, Rodes M, Roig M, Climent C, Rubio V, Sentis M, Burlina A: Optimization of allopurinol challenge: sample purification, protein intake control, and the use of orotidine response as a discriminative variable improve performance of the test for diagnosing ornithine carbamoyltransferase deficiency. Clin Chem. 1999 Jul;45(7):995-1001. [PubMed:10388475 ]
- Sugio K, Gazdar AF, Albores-Saavedra J, Kokkinakis DM: High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine in the pancreas of female Syrian hamsters. Carcinogenesis. 1996 Feb;17(2):303-9. [PubMed:8625455 ]
- Finkelstein JE, Hauser ER, Leonard CO, Brusilow SW: Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr. 1990 Dec;117(6):897-902. [PubMed:2246687 ]
- Harris ML, Oberholzer VG: Conditions affecting the colorimetry of orotic acid and orotidine in urine. Clin Chem. 1980 Mar;26(3):473-9. [PubMed:7363468 ]
- Jakobs C, Sweetman L, Nyhan WL, Gruenke L, Craig JC, Wadman SK: Stable isotope dilution analysis of orotic acid and uracil in amniotic fluid. Clin Chim Acta. 1984 Nov 15;143(2):123-33. [PubMed:6391739 ]
- Visek WJ: Arginine and disease states. J Nutr. 1985 Apr;115(4):532-41. [PubMed:3884753 ]
- Mizutani Y, Wada H, Fukushima M, Yoshida O, Nakanishi H, Li YN, Miki T: Prognostic significance of orotate phosphoribosyltransferase activity in bladder carcinoma. Cancer. 2004 Feb 15;100(4):723-31. [PubMed:14770427 ]
- Valik D, Sedova Z, Starha J, Zeman J, Hruba E, Dvorakova L: Acute hyperammonaemic encephalopathy in a female newborn caused by a novel, de novo mutation in the ornithine transcarbamylase gene. Acta Paediatr. 2004 May;93(5):710-1. [PubMed:15174800 ]
- Mills GC, Schmalstieg FC, Newkirk KE, Goldblum RM: Cytosine and orotic acid in urine of immunodeficient children. Clin Chem. 1979 Mar;25(3):419-24. [PubMed:262183 ]
- Paradis D, Giguere R, Auray-Blais C, Draper P, Lemieux B: An automated method for the determination of orotic acid in the urine of children being screened for metabolic disorders. Clin Biochem. 1980 Aug;13(4):160-3. [PubMed:7449082 ]
- Potter M, Hammond JW, Sim KG, Green AK, Wilcken B: Ornithine carbamoyltransferase deficiency: improved sensitivity of testing for protein tolerance in the diagnosis of heterozygotes. J Inherit Metab Dis. 2001 Feb;24(1):5-14. [PubMed:11286382 ]
- van Kuilenburg AB, van Lenthe H, Loffler M, van Gennip AH: Analysis of pyrimidine synthesis "de novo" intermediates in urine and dried urine filter- paper strips with HPLC-electrospray tandem mass spectrometry. Clin Chem. 2004 Nov;50(11):2117-24. Epub 2004 Sep 16. [PubMed:15375016 ]
- Brosnan ME, Brosnan JT: Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S. [PubMed:17513443 ]
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