| Record Information |
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| Version | 1.0 |
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| Created at | 2005-11-16 15:48:42 UTC |
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| Updated at | 2021-08-19 23:58:43 UTC |
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| NP-MRD ID | NP0001051 |
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| Secondary Accession Numbers | None |
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| Natural Product Identification |
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| Common Name | Dihydrouracil |
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| Description | Dihydrouracil 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. Dihydrouracil is an intermediate breakdown product of uracil. Dihydrouracil exists in all living organisms, ranging from bacteria to plants to humans. Within humans, dihydrouracil participates in a number of enzymatic reactions. In particular, dihydrouracil can be biosynthesized from uracil; which is mediated by the enzyme dihydropyrimidine dehydrogenase [NADP(+)]. The breakdown of uracil is a multistep reaction that leads to the production of beta-alanine. The reaction process begins with the enzyme known as dihydropyrimidine dehydrogenase (DHP), which catalyzes the reduction of uracil into dihydrouracil. Then the enzyme known as dihydropyrimidinase hydrolyzes dihydrouracil into N-carbamyl-beta-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-beta-alanine into beta-alanine. There is at least one metabolic disorder that is associated with altered levels of dihydrouracil. In particular, dihydropyrimidinase deficiency is an inborn metabolic disorder that leads to highly increased concentrations of dihydrouracil and 5,6-dihydrothymine, and moderately increased concentrations of uracil and thymine in urine. Dihydropyrimidinase deficiency can cause neurological and gastrointestinal problems in some affected individuals (OMIM: 222748 ). In particular, patients with dihydropyrimidinase deficiency exhibit a number of neurological abnormalities including 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. |
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| Structure | InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8) |
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| Synonyms | | Value | Source |
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| 2,4-Dioxotetrahydropyrimidine | ChEBI | | 5,6-Dihydro-2,4-dihydroxypyrimidine | ChEBI | | Dihydro-2,4(1H,3H)-pyrimidinedione | ChEBI | | DIHYDROPYRIMIDINE-2,4(1H,3H)-dione | ChEBI | | Dihydrouracile | ChEBI | | Hydrouracil | ChEBI | | 5,6-Dihydro-2,4(1H,3H)-pyrimidinedione | HMDB | | 5,6-Dihydrouracil | HMDB | | Dihydro-pyrimidine-2,4-dione | HMDB |
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| Chemical Formula | C4H6N2O2 |
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| Average Mass | 114.1026 Da |
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| Monoisotopic Mass | 114.04293 Da |
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| IUPAC Name | 1,3-diazinane-2,4-dione |
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| Traditional Name | dihydrouracil |
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| CAS Registry Number | 504-07-4 |
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| SMILES | O=C1CCNC(=O)N1 |
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| InChI Identifier | InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8) |
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| InChI Key | OIVLITBTBDPEFK-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, 500 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 |
| | Predicted Spectra |
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| Not Available | | Chemical Shift Submissions |
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| Not Available | | Species |
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| Species of Origin | |
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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 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. |
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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 | Pyrimidones |
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| Alternative Parents | |
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| 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
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| Molecular Framework | Aliphatic 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 | 279 - 281 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | 18600 mg/L @ 25 °C (est) | The Good Scents Company Information System | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| General References | - 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 ]
- 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. [PubMed:12798197 ]
- 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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:8581129 ]
- 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. [PubMed:12767347 ]
- Tan BR, McLeod HL: Pharmacogenetic influences on treatment response and toxicity in colorectal cancer. Semin Oncol. 2005 Feb;32(1):113-9. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:11936689 ]
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