You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information |
---|
Version | 4.0 |
---|
Status | Detected and Quantified |
---|
Creation Date | 2005-11-16 15:48:42 UTC |
---|
Update Date | 2020-10-09 20:57:30 UTC |
---|
HMDB ID | HMDB0000076 |
---|
Secondary Accession Numbers | |
---|
Metabolite Identification |
---|
Common Name | Dihydrouracil |
---|
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 extremely weak basic (essentially neutral) compound (based on its pKa). Dihydrouracil is an intermediate breakdown product of uracil. Dihydrouracil exists in all living organisms, ranging from bacteria 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(+)]. In addition, dihydrouracil can be converted into ureidopropionic acid; which is mediated by the enzyme dihydropyrimidinase. Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals (OMIM: 222748 ). In particular, patients with dihydropyrimidinase deficiency exhibit highly increased concentrations of Dihydrouracil and 5,6-dihydrothymine, and moderately increased concentrations of uracil and thymine can be detected in urine. In humans, dihydrouracil is involved in the metabolic disorder called the beta-ureidopropionase deficiency pathway. Outside of the human body, Dihydrouracil has been detected, but not quantified in, several different foods, such as white cabbages, rubus (blackberry, raspberry), medlars, sweet potato, and sparkleberries. This could make dihydrouracil a potential biomarker for the consumption of these foods. Dihydrouracil is a potentially toxic compound. Dihydrouracil, with regard to humans, has been found to be associated with several diseases such as colorectal cancer, hypertension, liver disease, and cerebral infarction; dihydrouracil has also been linked to the inborn metabolic disorder dihydropyrimidine dehydrogenase deficiency. 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. 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. Dihydropyrimidine dehydrogenase (DHP) catalyzes the reduction of uracil into Dihydrouracil then dihydropyrimidinase hydrolyzes Dihydrouracil into N-carbamyl-beta-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-beta-alanine into beta-alanine. |
---|
Structure | |
---|
Synonyms | Value | Source |
---|
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 |
|
---|
Chemical Formula | C4H6N2O2 |
---|
Average Molecular Weight | 114.1026 |
---|
Monoisotopic Molecular Weight | 114.042927446 |
---|
IUPAC Name | 1,3-diazinane-2,4-dione |
---|
Traditional Name | dihydrouracil |
---|
CAS Registry Number | 504-07-4 |
---|
SMILES | O=C1CCNC(=O)N1 |
---|
InChI Identifier | InChI=1S/C4H6N2O2/c7-3-1-2-5-4(8)6-3/h1-2H2,(H2,5,6,7,8) |
---|
InChI Key | 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 | |
---|
Ontology |
---|
|
Physiological effect | Health effect: |
---|
Disposition | Route of exposure: Source: Biological location: |
---|
Process | Naturally occurring process: |
---|
Role | Biological role: Industrial application: |
---|
Physical Properties |
---|
State | Solid |
---|
Experimental Properties | Property | Value | Reference |
---|
Melting Point | 279 - 281 °C | Not Available | Boiling Point | Not Available | Not Available | Water Solubility | Not Available | Not Available | LogP | Not Available | Not Available |
|
---|
Predicted Properties | |
---|
Spectra |
---|
| Spectrum Type | Description | Splash Key | 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 | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (1 TMS) | splash10-00di-5900000000-8af1b81502646fa5b417 | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (2 TMS) | splash10-0fdo-9750000000-d2aaeeba1cf962175f84 | Spectrum | GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-00di-9700000000-4adeeb2f4f5a1111afb7 | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (Non-derivatized) | splash10-00di-5900000000-8af1b81502646fa5b417 | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (Non-derivatized) | splash10-0fdo-9750000000-d2aaeeba1cf962175f84 | Spectrum | GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-0f6w-2940000000-3430a0e2d1819021af1d | Spectrum | GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-00di-3900000000-79f2d90a419b7469cb61 | Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-004l-9100000000-55536f0571922b6c69fe | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated) | splash10-03k9-9800000000-da772cea603c785c1df4 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated) | splash10-0a4i-9100000000-94a5f543e8c6be7b3204 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated) | splash10-0btc-9200000000-e9bf2ae82714a2a3a737 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive | splash10-014i-5900000000-0fe83e63f6e5d1347894 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - , negative | splash10-03xr-6900000000-08aca1bc7f27b0e7cb08 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , positive | splash10-014i-5900000000-53ea361c86b4f9fa284b | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - , positive | splash10-00di-9300000000-a8599c09cd21e2f84329 | Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-014i-2900000000-ad7f91d5265e53403dd6 | Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0603-9200000000-4b30a83fb454e5bbffb8 | Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0006-9000000000-ce54e3c860a95b0af401 | Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-03di-9800000000-d705e188f6700a76ef72 | Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0006-9000000000-a26409d69a4259731004 | Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0006-9000000000-f00c4df547660023bee4 | Spectrum | MS | Mass Spectrum (Electron Ionization) | splash10-03fu-9400000000-5b9edda3479e7d0a0d28 | Spectrum | 1D NMR | 1H NMR Spectrum | Not Available | Spectrum | 1D NMR | 1H NMR Spectrum | Not Available | Spectrum | 1D NMR | 13C NMR Spectrum | Not Available | Spectrum | 2D NMR | [1H,13C] 2D NMR Spectrum | Not Available | Spectrum |
|
---|
Biological Properties |
---|
Cellular Locations | |
---|
Biospecimen Locations | - Blood
- Cerebrospinal Fluid (CSF)
- Feces
- Saliva
- Urine
|
---|
Tissue Locations | - Fibroblasts
- Kidney
- Liver
- Prostate
|
---|
Pathways | |
---|
Normal Concentrations |
---|
| |
Blood | Detected and Quantified | 0.31 (0.02-1.63) uM | Adult (>18 years old) | Female | Normal | | details | Blood | Detected and Quantified | 0.31 (0.02-1.63) uM | Adult (>18 years old) | Both | Normal | | details | Blood | Detected and Quantified | 0.32 ( 0.10-0.74) uM | Adult (>18 years old) | Male | Normal | | details | Cerebrospinal Fluid (CSF) | Detected and Quantified | 2.1 +/- 1.0 uM | Adult (>18 years old) | Not Specified | Normal | | details | Feces | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Both | Normal | | details | Saliva | Detected and Quantified | 700 +/- 199 uM | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected and Quantified | 2168.16 +/- 127.94 uM | Adult (>18 years old) | Both | Normal | | details | Saliva | Detected and Quantified | 2000 +/- 223 uM | Adult (>18 years old) | Female | Normal | | details | Saliva | Detected and Quantified | 2000 +/- 223 uM | Adult (>18 years old) | Not Specified | Normal | | details | Saliva | Detected and Quantified | 2210 +/- 353 uM | Adult (>18 years old) | Not Specified | Normal | | details | Saliva | Detected and Quantified | 2240 +/- 380 uM | Adult (>18 years old) | Female | Normal | | details | Saliva | Detected and Quantified | 2350 +/- 654 uM | Adult (>18 years old) | Female | Normal | | details | Urine | Detected and Quantified | 0.79 umol/mmol creatinine | Adult (>18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 3.8 (2.1-8.3) umol/mmol creatinine | Adult (>18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 2.4 +/- 4.7 umol/mmol creatinine | Adult (>18 years old) | Male | Normal | | details | Urine | Detected and Quantified | 3.0 +/- 2.7 umol/mmol creatinine | Adult (>18 years old) | Female | Normal | | details | Urine | Detected and Quantified | 2.5-20 umol/mmol creatinine | Children (1 - 18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 12.2 +/- 6.2 umol/mmol creatinine | Infant (0-1 year old) | Both | Normal | | details | Urine | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Both | Normal | | details | Urine | Detected and Quantified | <3.4 umol/mmol creatinine | Infant (0-1 year old) | Both | Normal | | details |
|
---|
Abnormal Concentrations |
---|
| |
Cerebrospinal Fluid (CSF) | Detected and Quantified | 81.5 (46.0-117.0) uM | Adult (>18 years old) | Both | Dihydropyrimidine dehydrogenase (DPD) deficiency | | details | Feces | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Both | Colorectal cancer | | details | Feces | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Both | Colorectal cancer | | details | Urine | Detected and Quantified | 2.4 +/- 1.67 umol/mmol creatinine | Adult (>18 years old) | Both | Hypertension | | details | Urine | Detected and Quantified | 627.0 umol/mmol creatinine | Infant (0-1 year old) | Both | Dihydropyrimidine dehydrogenase (DPD) deficiency | | details | Urine | Detected and Quantified | 2.4 +/- 2.00 umol/mmol creatinine | Adult (>18 years old) | Both | Cerebral infarction | | details | Urine | Detected and Quantified | 2.8 +/- 1.9 umol/mmol creatinine | Adult (>18 years old) | Both | Malignancy | | details | Urine | Detected and Quantified | 2.7 +/- 1.9 umol/mmol creatinine | Adult (>18 years old) | Both | Liver dysfunction | | details | Urine | Detected and Quantified | 2.5 +/- 2.00 umol/mmol creatinine | Adult (>18 years old) | Both | Nephropathy | | details |
|
---|
Associated Disorders and Diseases |
---|
Disease References | Colorectal cancer |
---|
- 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 ]
| Dihydropyrimidine dehydrogenase deficiency |
---|
- 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 ]
- 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 ]
| Hypertension |
---|
- Hayashi K, Kidouchi K, Sumi S, Mizokami M, Orito E, Kumada K, Ueda R, Wada Y: Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. Clin Cancer Res. 1996 Dec;2(12):1937-41. [PubMed:9816152 ]
| Cerebral infarction |
---|
- Hayashi K, Kidouchi K, Sumi S, Mizokami M, Orito E, Kumada K, Ueda R, Wada Y: Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. Clin Cancer Res. 1996 Dec;2(12):1937-41. [PubMed:9816152 ]
| Liver disease |
---|
- Hayashi K, Kidouchi K, Sumi S, Mizokami M, Orito E, Kumada K, Ueda R, Wada Y: Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. Clin Cancer Res. 1996 Dec;2(12):1937-41. [PubMed:9816152 ]
|
|
---|
Associated OMIM IDs | - 114500 (Colorectal cancer)
- 274270 (Dihydropyrimidine dehydrogenase deficiency)
- 145500 (Hypertension)
|
---|
External Links |
---|
DrugBank ID | DB01849 |
---|
Phenol Explorer Compound ID | Not Available |
---|
FooDB ID | FDB030556 |
---|
KNApSAcK ID | Not Available |
---|
Chemspider ID | 629 |
---|
KEGG Compound ID | C00429 |
---|
BioCyc ID | DI-H-URACIL |
---|
BiGG ID | 34956 |
---|
Wikipedia Link | Dihydrouracil |
---|
METLIN ID | 285 |
---|
PubChem Compound | 649 |
---|
PDB ID | Not Available |
---|
ChEBI ID | 15901 |
---|
Food Biomarker Ontology | Not Available |
---|
VMH ID | 56DURA |
---|
MarkerDB ID | MDB00000040 |
---|
References |
---|
Synthesis Reference | Bhat, K. S.; Rao, A. S. Synthesis of uracil, 6-methyluracil and some dihydrouracils. Organic Preparations and Procedures International (1983), 15(5), 303-13. |
---|
Material Safety Data Sheet (MSDS) | Download (PDF) |
---|
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. [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 ]
- 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 ]
- 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 ]
- 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 ]
|
---|