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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-02-22 10:05:38 UTC
Update Date2020-11-09 23:16:01 UTC
HMDB IDHMDB0001857
Secondary Accession Numbers
  • HMDB01857
Metabolite Identification
Common Name1,3-Dimethyluric acid
Description1,3-Dimethyluric acid is a product of theophylline metabolism in man. 1,3-Dimethyluric acid is one of the purine components in urinary calculi. Methylated purines originate from the metabolism of methylxanthines (caffeine, theophylline and theobromine). Methyluric acids are indistinguishable from uric acid by simple methods routinely used in clinical laboratories, requiring the use of high-performance liquid chromatography (HPLC). Purine derivatives in urinary calculi could be considered markers of abnormal purine metabolism. The content of a purine derivative in stone depends on its average urinary excretion in the general population, similarity to the chemical structure of uric acid, and content of the latter in stone. This suggests that purines in stones represent a solid solution with uric acid as solvent. It is also plausible that methylxanthines, ubiquitous components of the diet and drugs, are involved in the pathogenesis of urolithiasis. Caffeine is metabolized via successive pathways mainly catalyzed by CYP1A2, xanthine oxidase or N-acetyltransferase-2 to give 14 different metabolites. CYP1A2 activity shows an inter-individual variability among the population. CYP1A2, an isoform of the CYP1A cytochrome P450 super-family, is involved in the metabolism of many drugs and plays a potentially important role in the induction of chemical carcinogenesis. (PMID: 11712316 , 15833286 , 3506820 , 15013152 , 4039734 ).
Structure
Data?1582752212
Synonyms
ValueSource
OxytheophyllineChEBI
1,3-DimethylateGenerator
1,3-Dimethylic acidGenerator
1,3-DimethylurateHMDB
Chemical FormulaC7H8N4O3
Average Molecular Weight196.1634
Monoisotopic Molecular Weight196.059640142
IUPAC Name1,3-dimethyl-2,3,6,7,8,9-hexahydro-1H-purine-2,6,8-trione
Traditional Name1,3-dimethyluric acid
CAS Registry Number944-73-0
SMILES
CN1C2=C(NC(=O)N2)C(=O)N(C)C1=O
InChI Identifier
InChI=1S/C7H8N4O3/c1-10-4-3(8-6(13)9-4)5(12)11(2)7(10)14/h1-2H3,(H2,8,9,13)
InChI KeyOTSBKHHWSQYEHK-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentXanthines
Alternative Parents
Substituents
  • Xanthine
  • 6-oxopurine
  • Purinone
  • Alkaloid or derivatives
  • Pyrimidone
  • Pyrimidine
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Lactam
  • Urea
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point408 - 410 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.52 mg/mL at 18 °CNot Available
LogP-0.52GASPARI,F & BONATI,M (1987)
Predicted Properties
PropertyValueSource
Water Solubility8.69 g/LALOGPS
logP-0.74ALOGPS
logP-1.1ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)7.74ChemAxon
pKa (Strongest Basic)-5.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area81.75 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity55.42 m³·mol⁻¹ChemAxon
Polarizability17.74 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00kr-1900000000-572b5e917ae798f7285dSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-01ot-1900000000-bbb1123e337bff47c690Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-02mr-7900000000-fad7e7de9dee95b2d94bSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-047i-6900000000-b985a0b78d94b88e5577Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0900000000-6845b92ac4775760f4e2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0005-0900000000-b12d2b6804ac76c77b2dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-08gi-9400000000-3767a7fbda9ed867cbc5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0900000000-f5b0e3ac88c5546199d9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0900000000-f914e8dc73864e65caffSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9300000000-ea85e3f13c8017afbbb3Spectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified4.758 +/- 2.472 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified7.63 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Shaykhutdinov RA,...
details
UrineDetected and Quantified1.5 (1.34-2.34) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified3.1 (1.3-6.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal adenoma
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothInflammatory bowel disease details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothColorectal Cancer details
UrineDetected and Quantified9.167 +/- 9.245 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal adenoma
details
UrineDetected and Quantified33.0 (21.8-52.0) umol/mmol creatinineAdult (>18 years old)Both
Asthma
details
Associated Disorders and Diseases
Disease References
Inflammatory bowel disease
  1. Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker A, Lucio M, Michalke B, Schmitt-Kopplin P, Fedorak R, Haller D: Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut. 2017 May;66(5):863-871. doi: 10.1136/gutjnl-2015-309940. Epub 2016 Feb 4. [PubMed:26848182 ]
Colorectal cancer
  1. Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ]
  2. 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 ]
Asthma
  1. Zydron M, Baranowski J, Baranowska I: Separation, pre-concentration, and HPLC analysis of methylxanthines in urine samples. J Sep Sci. 2004 Oct;27(14):1166-72. [PubMed:15537072 ]
Eosinophilic esophagitis
  1. (). Mordechai, Hien, and David S. Wishart. .
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022712
KNApSAcK IDNot Available
Chemspider ID63527
KEGG Compound IDNot Available
BioCyc IDCPD-14118
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID2822
PubChem Compound70346
PDB IDNot Available
ChEBI ID68447
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000346
References
Synthesis ReferenceTaylor, Edward C.; Sowinski, Frank. Reaction of 6-amino- and 6-hydrazinopyrimidines with diethyl azodicarboxylate. New method for C-5 functionalization of pyrimidines. Journal of Organic Chemistry (1974), 39(7), 907-10.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Orlando R, Padrini R, Perazzi M, De Martin S, Piccoli P, Palatini P: Liver dysfunction markedly decreases the inhibition of cytochrome P450 1A2-mediated theophylline metabolism by fluvoxamine. Clin Pharmacol Ther. 2006 May;79(5):489-99. [PubMed:16678550 ]
  2. Knoppert DC, Spino M, Beck R, Thiessen JJ, MacLeod SM: Cystic fibrosis: enhanced theophylline metabolism may be linked to the disease. Clin Pharmacol Ther. 1988 Sep;44(3):254-64. [PubMed:3046811 ]
  3. Miller M, Opheim KE, Raisys VA, Motulsky AG: Theophylline metabolism: variation and genetics. Clin Pharmacol Ther. 1984 Feb;35(2):170-82. [PubMed:6362955 ]
  4. Safranow K: [Identification and quantitation of purine derivatives in urinary calculi as markers of abnormal purine metabolism by using high-performance liquid chromatography (HPLC)]. Ann Acad Med Stetin. 2000;46:35-49. [PubMed:11712316 ]
  5. Safranow K, Machoy Z: Simultaneous determination of 16 purine derivatives in urinary calculi by gradient reversed-phase high-performance liquid chromatography with UV detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 May 25;819(2):229-35. [PubMed:15833286 ]
  6. Morris GS, Simmonds HA, Davies PM: Use of biological fluids for the rapid diagnosis of potentially lethal inherited disorders of human purine and pyrimidine metabolism. Biomed Chromatogr. 1986 Jun;1(3):109-18. [PubMed:3506820 ]
  7. Caubet MS, Comte B, Brazier JL: Determination of urinary 13C-caffeine metabolites by liquid chromatography-mass spectrometry: the use of metabolic ratios to assess CYP1A2 activity. J Pharm Biomed Anal. 2004 Feb 4;34(2):379-89. [PubMed:15013152 ]
  8. Miller CA, Slusher LB, Vesell ES: Polymorphism of theophylline metabolism in man. J Clin Invest. 1985 May;75(5):1415-25. [PubMed:4039734 ]