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Record Information |
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Version | 4.0 |
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Status | Detected and Quantified |
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Creation Date | 2005-11-16 15:48:42 UTC |
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Update Date | 2020-10-09 20:57:33 UTC |
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HMDB ID | HMDB0000079 |
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Secondary Accession Numbers | |
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Metabolite Identification |
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Common Name | Dihydrothymine |
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Description | Dihydrothymine (CAS: 696-04-8) is an intermediate breakdown product of thymine. Dihydropyrimidine dehydrogenase catalyzes the reduction of thymine into 5,6-dihydrothymine; then dihydropyrimidinase hydrolyzes 5,6-dihydrothymine 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, dihydrothymine 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. The most common neurological abnormalities that occur are intellectual disability, seizures, weak muscle tone (hypotonia), abnormally small head size (microcephaly), and autistic behaviours that affect communication and social interaction. Gastrointestinal problems that occur in dihydropyrimidinase deficiency include the backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting. |
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Structure | |
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Synonyms | Value | Source |
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(-)-(S)-5,6-Dihydrothymine | HMDB | (5S)-5-Methyl-1,3-diazinane-2,4-dione | HMDB | 5,6-Dihydro-5-methyluracil | HMDB | 5,6-Dihydrothymine | HMDB | 5-Methyl-5,6-dihydrouracil | HMDB | 5-Methyldihydropyrimidine-2,4(1H,3H)-dione | HMDB | Dihydro-5-methyl-2,4(1H,3H)-pyrimidinedione | HMDB | Dihydrothymine | HMDB |
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Chemical Formula | C5H8N2O2 |
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Average Molecular Weight | 128.131 |
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Monoisotopic Molecular Weight | 128.058577506 |
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IUPAC Name | (5S)-5-methyl-1,3-diazinane-2,4-dione |
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Traditional Name | (5S)-5-methyl-1,3-diazinane-2,4-dione |
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CAS Registry Number | 19140-80-8 |
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SMILES | C[C@H]1CNC(=O)NC1=O |
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InChI Identifier | InChI=1S/C5H8N2O2/c1-3-2-6-5(9)7-4(3)8/h3H,2H2,1H3,(H2,6,7,8,9)/t3-/m0/s1 |
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InChI Key | NBAKTGXDIBVZOO-VKHMYHEASA-N |
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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 | Not Available |
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Ontology |
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Physiological effect | Health effect: |
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Disposition | Route of exposure: Source: Biological location: |
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Process | Naturally occurring process: |
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Role | Biological role: |
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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 | Not Available | Not Available | Boiling Point | Not Available | Not Available | Water Solubility | Not Available | Not Available | LogP | Not Available | Not Available |
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Predicted Properties | |
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Spectra |
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| Spectrum Type | Description | Splash Key | View |
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GC-MS | GC-MS Spectrum - GC-MS (1 TMS) | splash10-000i-5900000000-0b84b9786838d29e07ab | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (2 TMS) | splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5 | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (Non-derivatized) | splash10-000i-5900000000-0b84b9786838d29e07ab | Spectrum | GC-MS | GC-MS Spectrum - GC-MS (Non-derivatized) | splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated) | splash10-004i-8900000000-db662635cbae4d48204b | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated) | splash10-0006-9000000000-c3960ffe99d74c617000 | Spectrum | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated) | splash10-0006-9000000000-9a6c2715f931ff084157 | Spectrum | MS | Mass Spectrum (Electron Ionization) | splash10-004l-9200000000-873ae62dcdf602237ec1 | 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 |
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Biological Properties |
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Cellular Locations | |
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Biospecimen Locations | - Blood
- Cerebrospinal Fluid (CSF)
- Feces
- Saliva
- Urine
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Tissue Locations | |
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Pathways | |
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Normal Concentrations |
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Blood | Expected but not Quantified | Not Quantified | Not Available | Not Available | Normal | | details | Cerebrospinal Fluid (CSF) | Detected and Quantified | 1.1 +/- 0.3 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 but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | Urine | Detected and Quantified | 0.4 umol/mmol creatinine | Adult (>18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 5.00 (0.00-10.00) umol/mmol creatinine | Adult (>18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 0-3 umol/mmol creatinine | Children (1 - 18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 2.4 (1.3-4.4) umol/mmol creatinine | Adult (>18 years old) | Both | Normal | | details | Urine | Detected and Quantified | 8.736 +/- 1.827 umol/mmol creatinine | Children (1 - 13 years old) | Not Specified | Normal | | details | Urine | Detected and Quantified | 0.40 (0.17-0.64) umol/mmol creatinine | Adult (>18 years old) | Male | Normal | | details | Urine | Detected and Quantified | <0.6 umol/mmol creatinine | Infant (0-1 year old) | Both | Normal | | details | Urine | Detected and Quantified | 0.57 (0.21-0.94) umol/mmol creatinine | Adult (>18 years old) | Female | Normal | | details |
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Abnormal Concentrations |
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Cerebrospinal Fluid (CSF) | Detected and Quantified | 0.0 - 24.0 uM | Not Specified | Both | Dihydropyrimidinase deficiency | | details | Cerebrospinal Fluid (CSF) | Detected and Quantified | 4.0 - 5.2 uM | Adult (>18 years old) | Not Specified | Beta-ureidopropionase deficiency | | details | Urine | Detected and Quantified | 11.664 +/- 5.285 umol/mmol creatinine | Children (1 - 13 years old) | Not Specified | Eosinophilic esophagitis | | details |
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Associated Disorders and Diseases |
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Disease References | Dihydropyrimidinase deficiency |
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- van Kuilenburg AB, Meijer J, Dobritzsch D, Meinsma R, Duran M, Lohkamp B, Zoetekouw L, Abeling NG, van Tinteren HL, Bosch AM: Clinical, biochemical and genetic findings in two siblings with a dihydropyrimidinase deficiency. Mol Genet Metab. 2007 Jun;91(2):157-64. Epub 2007 Mar 26. [PubMed:17383919 ]
| Beta-ureidopropionase deficiency |
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- van Kuilenburg AB, Meinsma R, Beke E, Assmann B, Ribes A, Lorente I, Busch R, Mayatepek E, Abeling NG, van Cruchten A, Stroomer AE, van Lenthe H, Zoetekouw L, Kulik W, Hoffmann GF, Voit T, Wevers RA, Rutsch F, van Gennip AH: beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities. Hum Mol Genet. 2004 Nov 15;13(22):2793-801. Epub 2004 Sep 22. [PubMed:15385443 ]
| Eosinophilic esophagitis |
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- (). Mordechai, Hien, and David S. Wishart. .
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Associated OMIM IDs | - 222748 (Dihydropyrimidinase deficiency)
- 613161 (Beta-ureidopropionase deficiency)
- 610247 (Eosinophilic esophagitis)
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External Links |
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DrugBank ID | Not Available |
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Phenol Explorer Compound ID | Not Available |
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FooDB ID | FDB021892 |
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KNApSAcK ID | Not Available |
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Chemspider ID | 589127 |
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KEGG Compound ID | C00906 |
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BioCyc ID | DIHYDRO-THYMINE |
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BiGG ID | Not Available |
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Wikipedia Link | Dihydrothymine |
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METLIN ID | Not Available |
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PubChem Compound | 676414 |
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PDB ID | Not Available |
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ChEBI ID | Not Available |
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Food Biomarker Ontology | Not Available |
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VMH ID | Not Available |
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MarkerDB ID | MDB00000043 |
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References |
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Synthesis Reference | Yamane, Tetsuo; Wyluda, Benjamin J.; Shulman, Robert G. Dihydrothymine from ultraviolet-irradiated DNA. Proceedings of the National Academy of Sciences of the United States of America (1967), 58(2), 439-42. |
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Material Safety Data Sheet (MSDS) | Download (PDF) |
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General References | - 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 ]
- 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 ]
- 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 ]
- Rosenbaum K, Jahnke K, Curti B, Hagen WR, Schnackerz KD, Vanoni MA: Porcine recombinant dihydropyrimidine dehydrogenase: comparison of the spectroscopic and catalytic properties of the wild-type and C671A mutant enzymes. Biochemistry. 1998 Dec 15;37(50):17598-609. [PubMed:9860876 ]
- Sumi S, Kidouchi K, Kondou M, Hayashi K, Dobashi K, Kouwaki M, Togari H, Wada Y: Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine. Int J Mol Med. 1998 Oct;2(4):477-82. [PubMed:9857238 ]
- Van Kuilenburg AB, Van Lenthe H, Van Gennip AH: Identification and tissue-specific expression of a NADH-dependent activity of dihydropyrimidine dehydrogenase in man. Anticancer Res. 1996 Jan-Feb;16(1):389-94. [PubMed:8615641 ]
- Kobayashi K, Sumi S, Kidouchi K, Mizuno I, Mohri N, Fukui T, Akamo Y, Takeyama H, Manabe T: [A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity]. Gan To Kagaku Ryoho. 1998 Jul;25(8):1217-9. [PubMed:9679586 ]
- Sumi S, Imaeda M, Kidouchi K, Ohba S, Hamajima N, Kodama K, Togari H, Wada Y: Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity. Am J Med Genet. 1998 Jul 24;78(4):336-40. [PubMed:9714435 ]
- 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 ]
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