ECMDB: Orotic acid (ECMDB00226) (M2MDB000094)

Identification Taxonomy Physical Properties Biological Properties Spectra Concentrations Links References Enzymes (2)Transporters (5)XML

Proteins (935)

Record Information

Version

2.0

Creation Date

2012-05-31 10:24:14 -0600

Update Date

2015-09-13 12:56:07 -0600

Secondary Accession Numbers

ECMDB00226

Identification

Name:

Orotic acid

Description

Orotic acid is a heterocyclic compound and an acid; it is also known as pyrimidinecarboxylic acid. It was once believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin but is instead manufactured in the body by intestinal flora. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotate phosphoribosyltransferase and orotidylate decarboxylase activity. (Wikipedia)

Structure

MOL SDF PDB SMILES InChI

Synonyms:

1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylate
1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylic acid
1,2,3,6-Tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylate
1,2,3,6-Tetrahydro-2,6-dioxo-4-Pyrimidinecarboxylic acid
1,2,3,6-Tetrahydro-2,6-dioxopyrimidin-4-carbonsaeure
2,6-Dihydroxy-4-pyrimidinecarboxylate
2,6-Dihydroxy-4-pyrimidinecarboxylic acid
2,6-Dihydroxypyrimidine-4-carboxylate
2,6-Dihydroxypyrimidine-4-carboxylic acid
2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylate
2,6-Dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acid
2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylate
2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid
6-Carboxy-2,4-dihydroxypyrimidine
6-Carboxyuracil
6-Uracilcarboxylate
6-Uracilcarboxylic acid
Acide orotique
Acido orotico
Acidum oroticum
Animal galactose factor
Lactinium
Molkensaeure
ORO
Orodin
Oropur
Orotate
Orotic acid
Orotonin
Orotonsan
Orotsaeure
Orotsaure
Oroturic
Orotyl
Uracil-6-carbosaeure
Uracil-6-carboxylate
Uracil-6-carboxylic acid
Vitamin B13
Whey factor

Chemical Formula:

C₅H₄N₂O₄

Weight:

Average: 156.0963
Monoisotopic: 156.017106626

InChI Key:

PXQPEWDEAKTCGB-UHFFFAOYSA-N

InChI:

InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)

CAS number:

65-86-1

IUPAC Name:

2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid

Traditional IUPAC Name:

orotic acid

SMILES:

OC(=O)C1=CC(=O)NC(=O)N1

Chemical Taxonomy

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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Diazines

Sub Class

Pyrimidines and pyrimidine derivatives

Direct Parent

Pyrimidinecarboxylic acids

Alternative Parents

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

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

pyrimidinemonocarboxylic acid (CHEBI:16742 )

Physical Properties

State:

Solid

Charge:

-1

Melting point:

345.5 °C

Experimental Properties:

Property	Value	Source
Water Solubility:	1.82 mg/mL at 18 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)]	PhysProp
LogP:	-0.83 [SANGSTER (1994)]	PhysProp

Predicted Properties

Property	Value	Source
Water Solubility	4.51 g/L	ALOGPS
logP	-0.89	ALOGPS
logP	-1.2	ChemAxon
logS	-1.5	ALOGPS
pKa (Strongest Acidic)	2.83	ChemAxon
pKa (Strongest Basic)	-6	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	95.5 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	33.27 m³·mol⁻¹	ChemAxon
Polarizability	12.46 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Biological Properties

Cellular Locations:

Cytoplasm

Reactions:

SMPDB Pathways:

Pyrimidine metabolism

PW000942

KEGG Pathways:

Drug metabolism - other enzymes ec00983
Metabolic pathways eco01100
Pyrimidine metabolism ec00240

EcoCyc Pathways:

uridine-5'-phosphate biosynthesis PWY-5686

Concentrations

Not Available

Spectra

Spectra:

Spectrum Type	Description	Splash Key
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-0udi-1982000000-b20f2ec9a2f1acc84ae1	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (3 TMS)	splash10-0zfr-2693000000-07bf11b5177412647d9b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-1982000000-b20f2ec9a2f1acc84ae1	View in MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0zfr-2693000000-07bf11b5177412647d9b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-1972000000-c04fb7381d3ca07c9b0a	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-06ri-6900000000-4ba5fde1f8f62c4a2ba2	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0229-9850000000-8164142820eb5162e753	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	View in JSpectraViewer
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)	splash10-03di-0900000000-81d73aed73c250fff3ae	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)	splash10-0006-9300000000-ecb08d1854a2789480d1	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)	splash10-0006-9100000000-15748a4c13636c42f4f9	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-02ti-4900000000-6fd6312d81f94faaaf11	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-03di-0900000000-1b7abf52e4a01cb85541	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-03di-0900000000-1b7abf52e4a01cb85541	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-03di-0900000000-3dff3caa5c10aff8ce46	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-02ti-4900000000-6fd6312d81f94faaaf11	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-004i-9000000000-351f585d58b38f6132de	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4r-0900000000-4e46209ca236b470bf7f	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-014i-9300000000-aa9cd31d715d134ee8dd	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-014i-9000000000-cdd01e740b6f9d1a909a	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-03di-1900000000-baf39ad8ab6f08fb1a7b	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0bt9-0900000000-1ad59feda583f2247b21	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-2900000000-0d0d27215e9f39a2a15b	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-918a38777f5d4e049697	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0900000000-d7bbee7f2dc7bb0c6a83	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03dl-7900000000-303fe3e06e98f518a2ee	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-b2c02975bbba65c2f1c6	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0bt9-0900000000-1ad59feda583f2247b21	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-2900000000-0d0d27215e9f39a2a15b	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-918a38777f5d4e049697	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0900000000-d7bbee7f2dc7bb0c6a83	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03dl-7900000000-303fe3e06e98f518a2ee	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-b2c02975bbba65c2f1c6	View in MoNA
MS	Mass Spectrum (Electron Ionization)	splash10-066r-9300000000-e5c3ef3304f93a38628c	View in MoNA
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
2D NMR	[1H,1H] 2D NMR Spectrum	Not Available	View in JSpectraViewer
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	View in JSpectraViewer

References

References:

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
Brosnan ME, Brosnan JT: Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S. Pubmed: 17513443
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
Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
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
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
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
Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. Pubmed: 2026685
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
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
van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. Pubmed: 17765195
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
Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72. Pubmed: 18402659
Visek WJ: Ammonia: its effects on biological systems, metabolic hormones, and reproduction. J Dairy Sci. 1984 Mar;67(3):481-98. Pubmed: 6371080
Visek WJ: Arginine and disease states. J Nutr. 1985 Apr;115(4):532-41. Pubmed: 3884753
Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
Zieve L: Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 1986;5(2):167-76. Pubmed: 3088083

Synthesis Reference:

Mitchell, Herschel K.; Nyc, Joseph F. Intermediates in the synthesis of orotic acid from oxalacetic ester and urea. Journal of the American Chemical Society (1947), 69 674-7.

Material Safety Data Sheet (MSDS)

Download (PDF)

Links

External Links:

Resource	Link
CHEBI ID	16742
HMDB ID	HMDB00226
Pubchem Compound ID	967
Kegg ID	C00295
ChemSpider ID	942
Wikipedia	Orotic acid
BioCyc ID	OROTATE
EcoCyc ID	OROTATE
Ligand Expo	ORO

Enzymes

Protein Details

1. Dihydroorotate dehydrogenase

General function:: Involved in catalytic activity
Specific function:: (S)-dihydroorotate + a quinone = orotate + a quinol
Gene Name:: pyrD
Uniprot ID:: P0A7E1
Molecular weight:: 36774

Reactions

(S)-dihydroorotate + a quinone = orotate + a quinol.

Protein Details

2. Orotate phosphoribosyltransferase

General function:: Involved in orotate phosphoribosyltransferase activity
Specific function:: Catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate to orotate, leading to the formation of orotidine monophosphate (OMP)
Gene Name:: pyrE
Uniprot ID:: P0A7E3
Molecular weight:: 23567

Reactions

Orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate.

Transporters

Protein Details

1. Outer membrane protein N

General function:: Involved in transporter activity
Specific function:: Non-specific porin
Gene Name:: ompN
Uniprot ID:: P77747
Molecular weight:: 41220

Protein Details

2. Outer membrane pore protein E

General function:: Involved in transporter activity
Specific function:: Uptake of inorganic phosphate, phosphorylated compounds, and some other negatively charged solutes
Gene Name:: phoE
Uniprot ID:: P02932
Molecular weight:: 38922

Protein Details

3. Aerobic C4-dicarboxylate transport protein

General function:: Involved in symporter activity
Specific function:: Responsible for the aerobic transport of the dicarboxylates fumarate, L- and D-malate and to a lesser extent succinate, from the periplasm across the inner membrane
Gene Name:: dctA
Uniprot ID:: P0A830
Molecular weight:: 45436

Protein Details

4. Outer membrane protein F

General function:: Involved in transporter activity
Specific function:: OmpF is a porin that forms passive diffusion pores which allow small molecular weight hydrophilic materials across the outer membrane. It is also a receptor for the bacteriophage T2
Gene Name:: ompF
Uniprot ID:: P02931
Molecular weight:: 39333

Protein Details

5. Outer membrane protein C

General function:: Involved in transporter activity
Specific function:: Forms passive diffusion pores which allow small molecular weight hydrophilic materials across the outer membrane
Gene Name:: ompC
Uniprot ID:: P06996
Molecular weight:: 40368

Orotic acid (ECMDB00226) (M2MDB000094)

Structure for #<Compound:0xa8cef588>

Enzymes

Reactions

Reactions

Transporters