MiMeDB: Showing metabocard for 4,5-Dihydroorotic acid (MMDBc0000352)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:35:56 UTC

Update Date

2024-04-30 19:31:54 UTC

Metabolite ID

MMDBc0000352

Metabolite Identification

Common Name

4,5-Dihydroorotic acid

Description

4,5-Dihydroorotic acid, also known as dihydroorotate or hydroorotate is a pyrimidinemonocarboxylic acid that results from the base-catalysed cyclisation of N-alpha-carbethoxyasparagine. It is classified as a secondary amide, a monocarboxylic acid, a pyrimidinemonocarboxylic acid and a N-acylurea. 4,5-Dihydroorotic acid is a derivative of orotic acid which serves as an intermediate in pyrimidine biosynthesis. 4,5-Dihydroorotic acid exists in all living species, ranging from bacteria to plants to humans. 4,5-Dihydroorotic acid is synthesized by the enzyme known as Dihydroorotase (EC 3.5.2.3) which converts carbamoyl aspartic acid into 4,5-dihydroorotic acid as part of the de novo pyrimidine biosynthesis pathway (PMID: 13163076 ). 4,5-Dihydroorotic acid is also a substrate for the enzyme known as dihydroorotate dehydrogenase (DHODH). In mammalian species, DHODH catalyzes the fourth step in the de novo pyrimidine biosynthesis pathway, which involves the ubiquinone-mediated oxidation of dihydroorotate to orotate and the reduction of flavin mononucleotide (FMN) to dihydroflavin mononucleotide (FMNH2). Inhibition of DHODH activity with teriflunomide (an immunomodulatory drug) or expression with RNA interference results in reduced ROS generation and consequent apoptosis of transformed skin and prostate epithelial cells. Mutations in the DHOD gene have been shown to cause Miller syndrome, also known as Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or post-axial acrofacial dystosis (PMID: 19915526 ).

Structure

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

Synonyms

Value	Source
5,6-Dihydro-orotic acid	ChEBI
DL-Dihydroortotic acid	ChEBI
Hydroorotic acid	ChEBI
5,6-Dihydro-orotate	Generator
DL-Dihydroortotate	Generator
Hydroorotate	Generator
4,5-Dihydroorotate	Generator
4,5-Dihydroorotic acid, (D)-isomer	MeSH
4,5-Dihydroorotic acid, (DL)-isomer	MeSH
4,5-Dihydroorotic acid, (L)-isomer	MeSH
5,6-Dihydroorotate	MeSH
L-Dihydroorotate	MeSH
Dihydroorotate	MeSH
(+)-2,6-dioxo-hexahydro-Pyrimidine-4-carboxylate	HMDB
(+)-2,6-dioxo-hexahydro-Pyrimidine-4-carboxylic acid	HMDB
(R)-2,6-dioxo-hexahydro-Pyrimidine-4-carboxylate	HMDB
(R)-2,6-dioxo-hexahydro-Pyrimidine-4-carboxylic acid	HMDB
(S)-2,6-dioxo-hexahydro-Pyrimidine-4-carboxylate	HMDB
(S)-2,6-dioxo-hexahydro-Pyrimidine-4-carboxylic acid	HMDB
2,6-dioxo-hexahydro-Pyrimidine-4-carboxylate	HMDB
2,6-dioxo-hexahydro-Pyrimidine-4-carboxylic acid	HMDB
L-Hydroorotate	HMDB
L-Hydroorotic acid	HMDB
R,S-Hydroorotate	HMDB

Molecular Formula

C₅H₆N₂O₄

Average Mass

158.1121

Monoisotopic Mass

158.03275669

IUPAC Name

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

Traditional Name

dihydroorotic acid

CAS Registry Number

Not Available

SMILES

OC(=O)C1CC(=O)NC(=O)N1

InChI Identifier

InChI=1S/C5H6N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h2H,1H2,(H,9,10)(H2,6,7,8,11)

InChI Key

UFIVEPVSAGBUSI-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Alpha amino acids and derivatives

Alternative Parents

Substituents

Alpha-amino acid or derivatives
N-acyl urea
Pyrimidone
Ureide
1,3-diazinane
Pyrimidine
Dicarboximide
Urea
Carbonic acid derivative
Azacycle
Monocarboxylic acid or derivatives
Carboxylic acid
Organoheterocyclic compound
Hydrocarbon derivative
Organic oxide
Organooxygen compound
Organonitrogen compound
Organopnictogen compound
Organic oxygen compound
Carbonyl group
Organic nitrogen compound
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

monocarboxylic acid (CHEBI:30865 )
N-acylurea (CHEBI:30865 )
secondary amide (CHEBI:30865 )
pyrimidinemonocarboxylic acid (CHEBI:30865 )

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Property	Value	Source
Water Solubility	12.7 g/L	ALOGPS
logP	-1.7	ALOGPS
logP	-1.5	ChemAxon
logS	-1.1	ALOGPS
pKa (Strongest Acidic)	3.28	ChemAxon
pKa (Strongest Basic)	-8.2	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	31.58 m³·mol⁻¹	ChemAxon
Polarizability	13.09 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

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-000f-9400000000-248b8d6d703ba73c2058	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-03di-3900000000-b0776f22820e6e570a09	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-059i-9700000000-c8ce0433c02db41880b9	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-00di-9000000000-56601203ef19b09212fe	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-006x-9000000000-b6342346ce51dd871eaa	2012-07-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0900000000-2ddb498acc970a567f6b	2016-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03dl-5900000000-4b73ae512e57466dd4e6	2016-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-d6c31a36d6fe5c68d9e1	2016-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-1900000000-c84801951eaa1da750f7	2016-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-4ae1d11ab20f903606c3	2016-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-aec3a40befb20e60f21b	2016-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-06r6-0900000000-86736ae769db7bc83c23	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-5900000000-f6e9e0cbdc2adf67aa89	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00dl-9000000000-aac58a007ab745825d74	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0900000000-b0c5e687f246809cdae9	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ox-6900000000-cb60b796898e6ca4336d	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-fccf5d7216b23cffed7a	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)		2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-29	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)		2012-12-05	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm

Biospecimen Locations

Feces
Prostate

Tissue Locations

Prostate

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0191855	Dihydroorotate dehydrogenase (quinone), mitochondrial	Unknown	Q02127	Homo sapiens
MMDBp0193901	CAD protein	Unknown	P27708	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Data Source	Reference
MMDBr0000680	4,5-Dihydroorotic acid	Orotic acid	dihydroorotate dehydrogenase (quinone)	VMH	10727948 9693067
MMDBr0007311	4,5-Dihydroorotic acid	Menaquinol 8	Not Available	VMH	30371894
MMDBr0007312	4,5-Dihydroorotic acid	Hydrogen peroxide	Not Available	VMH	30371894
MMDBr0007313	4,5-Dihydroorotic acid	Ureidosuccinic acid	Not Available	VMH; KEGG	30371894
MMDBr0007657	4,5-Dihydroorotic acid	Orotic acid	Not Available	VMH	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria	Bacteroidetes	117	Human stool; Human ; Human feces; Human appendix biopsy; Human saliva; Human gastric fluid; Human urine; Human subgingival plaque; Human supragingival plaque	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria	Actinobacteria	120	Human ; Human feces; Human sputum; Human saliva; Human supragingival plaque; Human subgingival plaque; Human pleural fluid plaque; Human dental plaque; Human nasopharyngeal swab; Human mucosa	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria	Firmicutes	364	Human feces; Human pleural fluid plaque; Pig ; Human ; Human stool; Human subgingival plaque; Cattle ; Human saliva	Metabolic reconstruction
Bacteria	Proteobacteria	173	Human feces; Human sputum; Human ; Human unknown; Pig ; Human pleural fluid plaque; Human dental plaque; Human nasal swab; Human stool; Human feces; pleural fluid plaque; bal	Metabolic reconstruction
Bacteria	Verrucomicrobia	1	Human ; Human feces	Metabolic reconstruction
Bacteria	Synergistetes	3	Human feces	Metabolic reconstruction
Bacteria	Spirochaetes	1	Human feces	Metabolic reconstruction
Archaea	Thaumarchaeota	1		Metabolic reconstruction
Bacteria	Fusobacteria	19	Human feces; Human	Metabolic reconstruction
Archaea	Euryarchaeota	5		Metabolic reconstruction
Bacteria	Planctomycetes	1	Human feces	Metabolic reconstruction
Archaea	Crenarchaeota	1		Metabolic reconstruction
Eukaryota/Fungi	Ascomycota	1	Human feces; Human saliva	Unknown

Exposure Sources

Source Type	Source Sub-type	Species	Data Source	Reference

Host Biospecimen and Location

Host and Biospecimen	Status	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified				HMDB
Human Prostate	Detected but not Quantified	Not Specified	Not Specified	Normal	HMDB	34986597
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	29808030

External Links

HMDB ID

HMDB0000528

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

FDB022096

KNApSAcK ID

Not Available

Chemspider ID

628

KEGG Compound ID

C00337

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

4,5-Dihydroorotic_acid

METLIN ID

5513

PubChem Compound

648

PDB ID

Not Available

ChEBI ID

30865

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

LIEBERMAN I, KORNBERG A: Enzymatic synthesis and breakdown of a pyrimidine, orotic acid. I. Dihydroortic acid, ureidosuccinic acid, and 5-carboxymethylhydantoin. J Biol Chem. 1954 Apr;207(2):911-24. [PubMed:13163076 ]
Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ: Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010 Jan;42(1):30-5. doi: 10.1038/ng.499. Epub 2009 Nov 13. [PubMed:19915526 ]

Showing metabocard for 4,5-Dihydroorotic acid (MMDBc0000352)

MOL for #<Metabolite:0x00007fecb30601b0>

3D MOL for #<Metabolite:0x00007fecb30601b0>

3D SDF for #<Metabolite:0x00007fecb30601b0>

3D-SDF for #<Metabolite:0x00007fecb30601b0>

PDB for #<Metabolite:0x00007fecb30601b0>

3D PDB for #<Metabolite:0x00007fecb30601b0>

SMILES for #<Metabolite:0x00007fecb30601b0>

INCHI for #<Metabolite:0x00007fecb30601b0>

Structure for #<Metabolite:0x00007fecb30601b0>

3D Structure for #<Metabolite:0x00007fecb30601b0>