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Record Information

Version

5.0

Status

Detected and Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2023-05-30 20:55:57 UTC

HMDB ID

HMDB0000226

Secondary Accession Numbers

HMDB00226

Metabolite Identification

Common Name

Orotic acid

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.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

View in JSmol View NMR Assignments View Stereo Labels

Synonyms

Value	Source
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

Chemical Formula

C₅H₄N₂O₄

Average Molecular Weight

156.0963

Monoisotopic Molecular Weight

156.017106626

IUPAC Name

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

Traditional Name

orotic acid

CAS Registry Number

65-86-1

SMILES

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

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)

InChI Key

PXQPEWDEAKTCGB-UHFFFAOYSA-N

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 )

Ontology

Physiological effect

Health effect

Digestive system disorder

Hepatobiliary disorder

Hepatic disorder

Liver damage (PMID: 31434538)

Nervous system disorder

Nerve damage (PMID: 31434538)

Disposition

Biological location

Non-excretory biofluid

Urine (PMID: 7449082)
Feces (PMID: 27275383)

Cellular substructure

Cytoplasm (HMDB: HMDB0000226)
Extracellular (HMDB: HMDB0000226)

Source

Exogenous

Exogenous (HMDB: HMDB0000226)

Food

Milk and milk product

Unfermented milk

Milk (Cow) (FooDB: FOOD00618)

Milk and milk products (FooDB: FOOD00863)

Endogenous

Endogenous (HMDB: HMDB0000226)

Process

Role

Biological role

Metabolite (HMDB: HMDB0000226)
Waste product (PMID: 35448883)

Industrial application

Pharmaceutical industry

Biomarker

Ornithine transcarbamylase deficiency (MarkerDB: MDB00000108)
N Acetylglutamate Synthase Deficiency (MarkerDB: MDB00000108)
Orotic Aciduria (MarkerDB: MDB00000108)

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
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 (1994)

Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct Type	Data Source	CCS Value (Å²)	Reference
[M-H]-	Astarita_neg	122.0	30932474
[M-H]-	Baker	125.2	30932474
[M+H]+	Baker	138.85	30932474
[M-H]-	Not Available	123.0	http://allccs.zhulab.cn/database/detail?ID=AllCCS00000366
[M+H]+	Not Available	138.85	http://allccs.zhulab.cn/database/detail?ID=AllCCS00000366

Predicted Molecular 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	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	133.441	31661259
DarkChem	[M-H]-	129.44	31661259
AllCCS	[M+H]+	133.07	32859911
AllCCS	[M-H]-	124.507	32859911
DeepCCS	[M+H]+	130.013	30932474
DeepCCS	[M-H]-	126.848	30932474
DeepCCS	[M-2H]-	163.833	30932474
DeepCCS	[M+Na]+	138.957	30932474
AllCCS	[M+H]+	133.1	32859911
AllCCS	[M+H-H2O]+	128.6	32859911
AllCCS	[M+NH4]+	137.3	32859911
AllCCS	[M+Na]+	138.5	32859911
AllCCS	[M-H]-	124.5	32859911
AllCCS	[M+Na-2H]-	125.8	32859911
AllCCS	[M+HCOO]-	127.2	32859911

Predicted Retention Times

Underivatized

Chromatographic Method	Retention Time	Reference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.	1.97 minutes	32390414
Predicted by Siyang on May 30, 2022	9.9591 minutes	33406817
Predicted by Siyang using ReTip algorithm on June 8, 2022	5.47 minutes	32390414
AjsUoB = Accucore 150 Amide HILIC with 10mM Ammonium Formate, 0.1% Formic Acid	194.3 seconds	40023050
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid	749.9 seconds	40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid	367.3 seconds	40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid	64.7 seconds	40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid	240.4 seconds	40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	70.5 seconds	40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid	283.8 seconds	40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid	295.2 seconds	40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)	363.3 seconds	40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid	647.0 seconds	40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid	108.3 seconds	40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid	859.9 seconds	40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	231.5 seconds	40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	288.0 seconds	40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate	770.3 seconds	40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA	265.7 seconds	40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water	376.1 seconds	40023050

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Orotic acid	OC(=O)C1=CC(=O)NC(=O)N1	2650.6	Standard polar	33892256
Orotic acid	OC(=O)C1=CC(=O)NC(=O)N1	1553.4	Standard non polar	33892256
Orotic acid	OC(=O)C1=CC(=O)NC(=O)N1	1989.9	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Orotic acid,1TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)[NH]1	1660.4	Semi standard non polar	33892256
Orotic acid,1TMS,isomer #2	C[Si](C)(C)N1C(=O)C=C(C(=O)O)[NH]C1=O	1759.8	Semi standard non polar	33892256
Orotic acid,1TMS,isomer #3	C[Si](C)(C)N1C(C(=O)O)=CC(=O)[NH]C1=O	1718.4	Semi standard non polar	33892256
Orotic acid,2TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C)C(=O)[NH]1	1776.9	Semi standard non polar	33892256
Orotic acid,2TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C)C(=O)[NH]1	1882.7	Standard non polar	33892256
Orotic acid,2TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C)C(=O)[NH]1	2153.2	Standard polar	33892256
Orotic acid,2TMS,isomer #2	C[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)N1[Si](C)(C)C	1776.5	Semi standard non polar	33892256
Orotic acid,2TMS,isomer #2	C[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)N1[Si](C)(C)C	1869.5	Standard non polar	33892256
Orotic acid,2TMS,isomer #2	C[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)N1[Si](C)(C)C	2114.8	Standard polar	33892256
Orotic acid,2TMS,isomer #3	C[Si](C)(C)N1C(C(=O)O)=CC(=O)N([Si](C)(C)C)C1=O	1849.0	Semi standard non polar	33892256
Orotic acid,2TMS,isomer #3	C[Si](C)(C)N1C(C(=O)O)=CC(=O)N([Si](C)(C)C)C1=O	1925.6	Standard non polar	33892256
Orotic acid,2TMS,isomer #3	C[Si](C)(C)N1C(C(=O)O)=CC(=O)N([Si](C)(C)C)C1=O	2119.8	Standard polar	33892256
Orotic acid,3TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C)C(=O)N1[Si](C)(C)C	1933.3	Semi standard non polar	33892256
Orotic acid,3TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C)C(=O)N1[Si](C)(C)C	1962.0	Standard non polar	33892256
Orotic acid,3TMS,isomer #1	C[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C)C(=O)N1[Si](C)(C)C	1920.7	Standard polar	33892256
Orotic acid,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)[NH]1	1891.3	Semi standard non polar	33892256
Orotic acid,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N1C(=O)C=C(C(=O)O)[NH]C1=O	1975.4	Semi standard non polar	33892256
Orotic acid,1TBDMS,isomer #3	CC(C)(C)[Si](C)(C)N1C(C(=O)O)=CC(=O)[NH]C1=O	1969.6	Semi standard non polar	33892256
Orotic acid,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C(C)(C)C)C(=O)[NH]1	2222.3	Semi standard non polar	33892256
Orotic acid,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C(C)(C)C)C(=O)[NH]1	2294.6	Standard non polar	33892256
Orotic acid,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C(C)(C)C)C(=O)[NH]1	2322.0	Standard polar	33892256
Orotic acid,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)N1[Si](C)(C)C(C)(C)C	2188.6	Semi standard non polar	33892256
Orotic acid,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)N1[Si](C)(C)C(C)(C)C	2300.7	Standard non polar	33892256
Orotic acid,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)[NH]C(=O)N1[Si](C)(C)C(C)(C)C	2300.5	Standard polar	33892256
Orotic acid,2TBDMS,isomer #3	CC(C)(C)[Si](C)(C)N1C(C(=O)O)=CC(=O)N([Si](C)(C)C(C)(C)C)C1=O	2305.5	Semi standard non polar	33892256
Orotic acid,2TBDMS,isomer #3	CC(C)(C)[Si](C)(C)N1C(C(=O)O)=CC(=O)N([Si](C)(C)C(C)(C)C)C1=O	2360.9	Standard non polar	33892256
Orotic acid,2TBDMS,isomer #3	CC(C)(C)[Si](C)(C)N1C(C(=O)O)=CC(=O)N([Si](C)(C)C(C)(C)C)C1=O	2288.1	Standard polar	33892256
Orotic acid,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C(C)(C)C)C(=O)N1[Si](C)(C)C(C)(C)C	2477.5	Semi standard non polar	33892256
Orotic acid,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C(C)(C)C)C(=O)N1[Si](C)(C)C(C)(C)C	2575.2	Standard non polar	33892256
Orotic acid,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)C1=CC(=O)N([Si](C)(C)C(C)(C)C)C(=O)N1[Si](C)(C)C(C)(C)C	2324.8	Standard polar	33892256

Spectra

Biological Properties

Cellular Locations

Cytoplasm (predicted from logP)

Biospecimen Locations

Amniotic Fluid
Blood
Feces
Saliva
Urine

Tissue Locations

Liver
Pancreas
Placenta

Pathways

Name	SMPDB/PathBank	KEGG
Pyrimidine metabolism	Not Available
Beta Ureidopropionase Deficiency		Not Available
UMP Synthase Deficiency (Orotic Aciduria)		Not Available
Dihydropyrimidinase Deficiency		Not Available
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Amniotic Fluid	Detected and Quantified	0.27 +/- 0.25 uM	Adult (>18 years old)	Female	Normal	16139832	details
Blood	Detected and Quantified	5.0 +/- 0.4 uM	Adult (>18 years old)	Both	Normal	7877593	details
Blood	Detected and Quantified	0.89 +/- 0.63 uM	Adult (>18 years old)	Both	Normal	16139832	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details
Blood	Detected and Quantified	2.874 +/- 8.0460 uM	Adult (>18 years old)	Both	Normal	12675874	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Normal	27609529	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	27543620	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	25037050	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Not Specified	Normal	25985090	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	29808030	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Urine	Detected and Quantified	<3 umol/mmol creatinine	Newborn (0-30 days old)	Not Specified	Normal	26971250	details
Urine	Detected and Quantified	2.05 +/- 0.15 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	Analysis of 40 NI...	details
Urine	Detected and Quantified	0.061 +/- 0.003 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	16460720	details
Urine	Detected and Quantified	0.49 - 3.44 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	22019295	details
Urine	Detected and Quantified	2.07 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	24909877	details
Urine	Detected and Quantified	0-5 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	24909877	details
Urine	Detected and Quantified	0.4 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	30817767	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details
Urine	Detected and Quantified	1.05 +/- 1.22 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	7449082	details
Urine	Detected and Quantified	<20 umol/mmol creatinine	Newborn (0-30 days old)	Male	Normal	12697901	details
Urine	Detected and Quantified	0.0350-0.260 umol/mmol creatinine	Adult (>18 years old)	Female	Normal	Physician's Guide...	details
Urine	Detected and Quantified	0.0800-0.440 umol/mmol creatinine	Children (1-13 years old)	Both	Normal	2044610	details
Urine	Detected and Quantified	1.3-5.3 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	Hereditary Orotic...	details
Urine	Detected and Quantified	1.0-3.2 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	Hereditary Orotic...	details
Urine	Detected and Quantified	0.5-3.3 umol/mmol creatinine	Children (1-13 years old)	Both	Normal	Hereditary Orotic...	details
Urine	Detected and Quantified	0.26-3.20 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Hereditary Orotic...	details
Urine	Detected and Quantified	<4.33 umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	BC Children's Hos...	details
Urine	Detected and Quantified	0-5 umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	BC Children's Hos...	details
Urine	Detected and Quantified	0.63 +/- 0.21 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Geigy Scientific ...	details
Urine	Detected and Quantified	1.05 +/- 1.22 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	2026685	details
Urine	Detected and Quantified	0.16 +/- 0.12 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	16139832	details
Urine	Detected and Quantified	0.23 +/- 0.13 umol/mmol creatinine	Children (1-13 years old)	Both	Normal	16139832	details
Urine	Detected and Quantified	9.9 +/- 7.1 umol/mmol creatinine	Children (1-13 years old)	Both	Normal	10388475	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected and Quantified	38.506 +/- 91.954 uM	Adult (>18 years old)	Both	Uremia	12675874	details
Blood	Detected and Quantified	0.94 +/- 0.78 uM	Adult (>18 years old)	Both	Canavan disease	16139832	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Ulcerative colitis	27609529	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal cancer	27015276	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal cancer	25037050	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Crohns disease	27609529	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Unclassified IBD	27609529	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Both	Ulcerative colitis	27609529	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Both	Crohns disease	27609529	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal Cancer	27275383	details
Urine	Detected and Quantified	5.6 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Orotic Aciduria hereditary	Hereditary Orotic...	details
Urine	Detected and Quantified	5.4 umol/mmol creatinine	Newborn (0-30 days old)	Male	Phosphoenolpyruvate Carboxykinase Deficiency 1, Cytosolic	26971250	details
Urine	Detected and Quantified	2-2800 umol/mmol creatinine	Children (1-13 years old)	Male	OTC-deficiency	3202644	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Bladder cancer	28157703	details
Urine	Detected and Quantified	44.16(0.72-642.79) umol/mmol creatinine	Children (1-13 years old)	Both	Lysinuric protein intolerance (LPI) syndrome	7254935	details
Urine	Detected and Quantified	59-282 umol/mmol creatinine	Adult (>18 years old)	Both	Hyperornithinemia–Hyperammonemia-Homocitrullinuria syndrome	3106719	details
Urine	Detected and Quantified	8.24 umol/mmol creatinine	Adult (>18 years old)	Female	Orotic aciduria I	25757096	details
Urine	Detected and Quantified	>20 umol/mmol creatinine	Newborn (0-30 days old)	Male	Ornithine transcarbamylase deficiency	12697901	details
Urine	Detected and Quantified	0.720-2339 umol/mmol creatinine	Children (1-13 years old)	Male	N-acetylglutamate synthetase deficiency	2044610	details
Urine	Detected and Quantified	66.667-640 umol/mmol creatinine	Infant (0-1 year old)	Not Specified	Orotic Aciduria hereditary	Hereditary Orotic...	details
Urine	Detected and Quantified	293.333-573.333 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Orotic Aciduria hereditary	Hereditary Orotic...	details
Urine	Detected and Quantified	1000 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Orotic Aciduria hereditary	Hereditary Orotic...	details
Urine	Detected and Quantified	1.4-3.2 umol/mmol creatinine	Adult (>18 years old)	Male	Orotic Aciduria hereditary	Hereditary Orotic...	details
Urine	Detected and Quantified	427.09-2989.61 umol/mmol creatinine	Adult (>18 years old)	Not Specified	Orotic Aciduria hereditary	Hereditary Orotic...	details
Urine	Detected and Quantified	253.2 +/- 540.0 umol/mmol creatinine	Children (1-13 years old)	Not Specified	OTC-deficiency	10388475	details
Urine	Detected and Quantified	6.11 +/- 5.48 umol/mmol creatinine	Adult (>18 years old)	Both	Canavan disease	16139832	details

Associated Disorders and Diseases

Disease References

Canavan disease
Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, Di Pietro V, Ceccarelli L, Donzelli S, Francis JS, Giardina B: Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem. 2005 Nov;38(11):997-1008. Epub 2005 Sep 1. [PubMed:16139832 ]
Uremia
Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jorres A, Lemke HD, Massy ZA, Passlick-Deetjen J, Rodriguez M, Stegmayr B, Stenvinkel P, Tetta C, Wanner C, Zidek W: Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003 May;63(5):1934-43. doi: 10.1046/j.1523-1755.2003.00924.x. [PubMed:12675874 ]
Colorectal cancer
Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ] Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016. [PubMed:27015276 ] Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Crohn's disease
Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
Ulcerative colitis
Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
Ornithine transcarbamylase deficiency
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 ] Kopin AS, McBride EW, Chen C, Freidinger RM, Chen D, Zhao CM, Beinborn M: Identification of a series of CCK-2 receptor nonpeptide agonists: sensitivity to stereochemistry and a receptor point mutation. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5525-30. doi: 10.1073/pnas.0831223100. Epub 2003 Apr 15. [PubMed:12697901 ] Drogari E, Leonard JV: Late onset ornithine carbamoyl transferase deficiency in males. Arch Dis Child. 1988 Nov;63(11):1363-7. [PubMed:3202644 ]
Orotic aciduria I
Grohmann K, Lauffer H, Lauenstein P, Hoffmann GF, Seidlitz G: Hereditary orotic aciduria with epilepsy and without megaloblastic anemia. Neuropediatrics. 2015 Apr;46(2):123-5. doi: 10.1055/s-0035-1547341. Epub 2015 Mar 10. [PubMed:25757096 ] G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium. Webster DR, Becroft DO, van Gennip AH, Van Kuilenburg AP. (2014). Hereditary Orotic Aciduria and Other Disorders of Pyrimidine Metabolism. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY. http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62636333. McGraw-Hill.
N-acetylglutamate synthetase deficiency
Schubiger G, Bachmann C, Barben P, Colombo JP, Tonz O, Schupbach D: N-acetylglutamate synthetase deficiency: diagnosis, management and follow-up of a rare disorder of ammonia detoxication. Eur J Pediatr. 1991 Mar;150(5):353-6. [PubMed:2044610 ]
Hyperornithinemia-hyperammonemia-homocitrullinuria
Rodes M, Ribes A, Pineda M, Alvarez L, Fabregas I, Fernandez Alvarez E, Coude FX, Grimber G: A new family affected by the syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria. J Inherit Metab Dis. 1987;10(1):73-81. [PubMed:3106719 ]
Lysinuric protein intolerance
Rajantie J: Orotic aciduria in lysinuric protein intolerance: dependence on the urea cycle intermediates. Pediatr Res. 1981 Feb;15(2):115-9. doi: 10.1203/00006450-198102000-00006. [PubMed:7254935 ]
Phosphoenolpyruvate Carboxykinase Deficiency 1, Cytosolic
Santra S, Cameron JM, Shyr C, Zhang L, Drogemoller B, Ross CJ, Wasserman WW, Wevers RA, Rodenburg RJ, Gupte G, Preece MA, van Karnebeek CD: Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis. Mol Genet Metab. 2016 May;118(1):21-7. doi: 10.1016/j.ymgme.2016.03.001. Epub 2016 Mar 4. [PubMed:26971250 ]

Associated OMIM IDs

271900 (Canavan disease)
114500 (Colorectal cancer)
266600 (Crohn's disease)
311250 (Ornithine transcarbamylase deficiency)
258900 (Orotic aciduria I)
608300 (N-acetylglutamate synthetase deficiency)
238970 (Hyperornithinemia-hyperammonemia-homocitrullinuria)
222700 (Lysinuric protein intolerance)
261680 (Phosphoenolpyruvate Carboxykinase Deficiency 1, Cytosolic)

External Links

DrugBank ID

DB02262

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Wikipedia Link

METLIN ID

PubChem Compound

PDB ID

Not Available

ChEBI ID

16742

Food Biomarker Ontology

Not Available

VMH ID

OROT

MarkerDB ID

MDB00000108

Good Scents ID

rw1099361

References

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)

General References

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 ]
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 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Enzymes

Enzyme Details

1. Dihydroorotate dehydrogenase (quinone), mitochondrial

General function:: Involved in catalytic activity
Specific function:: Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Gene Name:: DHODH
Uniprot ID:: Q02127
Molecular weight:: 42866.93

Reactions

L-Dihydroorotic acid + a quinone → Orotic acid + a quinol	details
L-Dihydroorotic acid + Quinone → Orotic acid + Hydroquinone	details

Enzyme Details

2. Uridine 5'-monophosphate synthase

General function:: Involved in catalytic activity
Specific function:: Not Available
Gene Name:: UMPS
Uniprot ID:: P11172
Molecular weight:: 52221.075

Reactions

Orotidylic acid + Pyrophosphate → Orotic acid + Phosphoribosyl pyrophosphate	details

Showing metabocard for Orotic acid (HMDB0000226)

MOL for HMDB0000226 (Orotic acid)

3D MOL for HMDB0000226 (Orotic acid)

3D SDF for HMDB0000226 (Orotic acid)

3D-SDF for HMDB0000226 (Orotic acid)

PDB for HMDB0000226 (Orotic acid)

3D PDB for HMDB0000226 (Orotic acid)

SMILES for HMDB0000226 (Orotic acid)

INCHI for HMDB0000226 (Orotic acid)

Structure for HMDB0000226 (Orotic acid)

3D Structure for HMDB0000226 (Orotic acid)

Experimental Collision Cross Sections

Predicted Collision Cross Sections

Predicted Retention Times

Underivatized

Predicted Kovats Retention Indices

Underivatized

Derivatized

Enzymes

Reactions

Reactions