T3DB: Dihydrouracil

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation XML

Record Information

Version

2.0

Creation Date

2014-08-29 06:28:48 UTC

Update Date

2018-03-21 17:46:23 UTC

Accession Number

T3D4333

Identification

Common Name

Dihydrouracil

Class

Small Molecule

Description

Dihydrouracil is an intermediate breakdown product of uracil. Dihydropyrimidine dehydrogenase (DHP) catalyzes the reduction of uracil into 5,6-dihydrouracil then dihydropyrimidinase hydrolyzes 5,6-dihydrouracil into N-carbamyl-beta-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-beta-alanine into beta-alanine. When present at abnormally high levels, dihydrouracil can be toxic although the mechanism of toxicity is not clear. In particular, patients with dihydropyrimidinase deficiency exhibit highly increased concentrations of 5,6-dihydrouracil and 5,6-dihydrothymine, and moderately increased concentrations of uracil and thymine can be detected in urine. Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals (OMIM: 222748). The neurological abnormalities that occur most often in people with dihydropyrimidinase deficiency are intellectual disability, seizures, weak muscle tone (hypotonia), an abnormally small head size (microcephaly), and autistic behaviours that affect communication and social interaction. Gastrointestinal problems that occur in dihydropyrimidinase deficiency include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting. The direct measurement of the activity of DHP in patients has been hampered by the fact that the enzyme is expressed almost exclusively in liver tissue.

Compound Type

Animal Toxin
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
5,6-Dihydro-2,4(1H,3H)-pyrimidinedione
5,6-Dihydro-2,4-dihydroxypyrimidine
5,6-Dihydrouracil
Dihydro-2,4(1H,3H)-pyrimidinedione
Dihydro-pyrimidine-2,4-dione
Dihydrouracile
Hydrouracil

Chemical Formula

C₄H₆N₂O₂

Average Molecular Mass

114.103 g/mol

Monoisotopic Mass

114.043 g/mol

CAS Registry Number

504-07-4

IUPAC Name

1,3-diazinane-2,4-dione

Traditional Name

dihydrouracil

SMILES

OC1=NC(O)=NCC1

InChI Identifier

InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8)

InChI Key

InChIKey=OIVLITBTBDPEFK-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as pyrimidones. Pyrimidones are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Diazines

Sub Class

Pyrimidines and pyrimidine derivatives

Direct Parent

Pyrimidones

Alternative Parents

Substituents

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

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

pyrimidone (CHEBI:15901 )
a base derivative (DI-H-URACIL )
a pyrimidine-related compound (DI-H-URACIL )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Membrane
Nucleus

Biofluid Locations

Not Available

Tissue Locations

Fibroblasts
Kidney
Liver
Prostate

Pathways

Name	SMPDB Link	KEGG Link
Beta-Alanine Metabolism	SMP00007	map00410
Pyrimidine Metabolism	SMP00046	map00240
Dihydropyrimidinase Deficiency	SMP00178	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	279 - 281°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	25.9 g/L	ALOGPS
logP	-1.3	ALOGPS
logP	-1.2	ChemAxon
logS	-0.64	ALOGPS
pKa (Strongest Acidic)	11.73	ChemAxon
pKa (Strongest Basic)	-7.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	58.2 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	25.75 m³·mol⁻¹	ChemAxon
Polarizability	10.13 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

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-00di-9700000000-4adeeb2f4f5a1111afb7	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (1 TMS)	splash10-00di-5900000000-8af1b81502646fa5b417	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0fdo-9750000000-d2aaeeba1cf962175f84	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-9700000000-4adeeb2f4f5a1111afb7	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-00di-5900000000-8af1b81502646fa5b417	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0fdo-9750000000-d2aaeeba1cf962175f84	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0f6w-2940000000-3430a0e2d1819021af1d	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-3900000000-79f2d90a419b7469cb61	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-004l-9100000000-55536f0571922b6c69fe	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-03k9-9800000000-da772cea603c785c1df4	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0a4i-9100000000-94a5f543e8c6be7b3204	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-0btc-9200000000-e9bf2ae82714a2a3a737	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-014i-5900000000-0fe83e63f6e5d1347894	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-03xr-6900000000-08aca1bc7f27b0e7cb08	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-014i-5900000000-53ea361c86b4f9fa284b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-00di-9300000000-a8599c09cd21e2f84329	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-01b9-9500000000-03c8b6a5b2dc3625d5d3	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-0ab9-9000000000-331f648f78f506788b99	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-052f-9000000000-824aa91d3f2de539f0bd	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-014i-2900000000-ad7f91d5265e53403dd6	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0603-9200000000-4b30a83fb454e5bbffb8	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-ce54e3c860a95b0af401	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-9800000000-d705e188f6700a76ef72	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-a26409d69a4259731004	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-f00c4df547660023bee4	2015-05-27	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-014i-0900000000-b8f2cf36966bbbbb3285	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-014i-9500000000-44775319047d2eddad49	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-052f-9000000000-3cb7005ca8389854848e	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03dl-7900000000-9d78d5698ad7865d1789	2021-09-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-997cffdd9ad85c899225	2021-09-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-a88e812ae86e53f6c2d6	2021-09-25	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-03fu-9400000000-5b9edda3479e7d0a0d28	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 15.08 MHz, DMSO-d6, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB01849

HMDB ID

HMDB00076

PubChem Compound ID

649

ChEMBL ID

Not Available

ChemSpider ID

629

KEGG ID

C00429

UniProt ID

Not Available

OMIM ID

ChEBI ID

15901

BioCyc ID

DI-H-URACIL

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

DUC

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Link

General References

Van Kuilenburg AB, Stroomer AE, Van Lenthe H, Abeling NG, Van Gennip AH: New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid? Biochem J. 2004 Apr 1;379(Pt 1):119-24. [14705962 ]
Grem JL: Intratumoral molecular or genetic markers as predictors of clinical outcome with chemotherapy in colorectal cancer. Semin Oncol. 2005 Feb;32(1):120-7. [15726514 ]
Assmann B, Hoffmann GF, Wagner L, Brautigam C, Seyberth HW, Duran M, Van Kuilenburg AB, Wevers R, Van Gennip AH: Dihydropyrimidinase deficiency and congenital microvillous atrophy: coincidence or genetic relation? J Inherit Metab Dis. 1997 Sep;20(5):681-8. [9323563 ]
Megyeri A, Bacso Z, Shields A, Eliason JF: Development of a stereological method to measure levels of fluoropyrimidine metabolizing enzymes in tumor sections using laser scanning cytometry. Cytometry A. 2005 Apr;64(2):62-71. [15729713 ]
Nakamura A, Kikuchi K, Ohishi T, Masuike T: [Assay method for uracil, dihydrouracil, 5-fluorouracil and 5-fluoro-5, 6-dihydrouracil by high-performance liquid chromatography]. Gan To Kagaku Ryoho. 2004 Mar;31(3):381-6. [15045945 ]
van Lenthe H, van Kuilenburg AB, Ito T, Bootsma AH, van Cruchten A, Wada Y, van Gennip AH: Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. Clin Chem. 2000 Dec;46(12):1916-22. [11106323 ]
Sumi S, Kidouchi K, Ohba S, Wada Y: Automated screening system for purine and pyrimidine metabolism disorders using high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995 Oct 20;672(2):233-9. [8581129 ]
Hofmann U, Schwab M, Seefried S, Marx C, Zanger UM, Eichelbaum M, Murdter TE: Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):371-80. [12798197 ]
Shen GP, Galick H, Inoue M, Wallace SS: Decline of nuclear and mitochondrial oxidative base excision repair activity in late passage human diploid fibroblasts. DNA Repair (Amst). 2003 Jun 11;2(6):673-93. [12767347 ]
Tan BR, McLeod HL: Pharmacogenetic influences on treatment response and toxicity in colorectal cancer. Semin Oncol. 2005 Feb;32(1):113-9. [15726513 ]
Garcia AA, Blessing JA, Lenz HJ, Darcy KM, Mannel RS, Miller DS, Husseinzadeh N: Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study. Gynecol Oncol. 2005 Mar;96(3):810-7. [15721430 ]
Schneider S, Uchida K, Brabender J, Baldus SE, Yochim J, Danenberg KD, Salonga D, Chen P, Tsao-Wei D, Groshen S, Hoelscher AH, Schneider PM, Danenberg PV: Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after neoadjuvant three-modality treatment in patients with esophageal cancer. J Am Coll Surg. 2005 Mar;200(3):336-44. [15737843 ]
Jiang H, Jiang J, Hu P, Hu Y: Measurement of endogenous uracil and dihydrouracil in plasma and urine of normal subjects by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Mar 25;769(1):169-76. [11936689 ]
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. [19212411 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Dihydrouracil (T3D4333)

Structure for T3D4333: Dihydrouracil