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Record Information
StatusDetected and Quantified
Creation Date2006-05-22 15:12:32 UTC
Update Date2018-03-20 06:18:26 UTC
Secondary Accession Numbers
  • HMDB03099
Metabolite Identification
Common Name1-Methyluric acid
Description1-Methyluric acid is one of the three main theophylline metabolites in man. 1-Methyluric acid is one of the purine components in urinary calculi. Methylated purines originate from the metabolism of methylxanthines (caffeine, theophylline, and theobromine). Methyluric acids can be distinguished from uric acid via 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 superfamily, 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 , 9890610 ).
Chemical FormulaC6H6N4O3
Average Molecular Weight182.1368
Monoisotopic Molecular Weight182.043990078
IUPAC Name1-methyl-2,3,6,7,8,9-hexahydro-1H-purine-2,6,8-trione
Traditional Name1-methyluric acid
CAS Registry Number708-79-2
InChI Identifier
Chemical Taxonomy
DescriptionThis compound 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
Sub ClassPurines and purine derivatives
Direct ParentXanthines
Alternative Parents
  • 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

Biological location:


  Biofluid and excreta:

  Organ and components:




Naturally occurring process:

  Biological process:

    Biochemical pathway:


Biological role:

Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility5 mg/mLNot Available
LogP-0.57GASPARI,F & BONATI,M (1987)
Predicted Properties
Water Solubility3.23 g/LALOGPS
pKa (Strongest Acidic)7.67ChemAxon
pKa (Strongest Basic)-6.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area90.54 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity50.53 m³·mol⁻¹ChemAxon
Polarizability15.73 ųChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0far-2900000000-7c88ba8c892ca8263473View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-0900000000-f2e42cd67ce1106bed63View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-0900000000-9fd2304504c5787dc255View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-9000000000-6069b457c0c038edb8dfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0006-0900000000-f47eba015e7f8d9f21a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0900000000-9fb7b528d968cab88bd3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0059-1900000000-eb2d1569b5bdfeef979aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000w-9300000000-065aa3463c121bf31312View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1900000000-62dd716e79c8fa6f5ee0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-3900000000-bf85a8ad5b7719f36abaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-7db60439b29417bbbe0dView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Amniotic Fluid
  • Blood
  • Feces
  • Urine
Tissue Location
  • Kidney
  • Liver
Caffeine MetabolismThumbThumb?image type=greyscaleThumb?image type=simpleMap00232
Normal Concentrations
Amniotic FluidDetected and Quantified0.51 +/- 0.044 uMAdult (>18 years old)BothNormal details
BloodDetected but not Quantified Adult (>18 years old)Both
BloodDetected but not Quantified Adult (>18 years old)Both
BloodExpected but not Quantified Not AvailableNot AvailableNormal
    FecesDetected but not Quantified Adult (>18 years old)Both
    FecesDetected but not Quantified Adult (>18 years old)Both
    UrineDetected and Quantified13.95 +/- 10.65 umol/mmol creatinineChildren (1-13 years old)BothNormal details
    UrineDetected and Quantified25.20 +/- 13.5 umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
    Abnormal Concentrations
    FecesDetected but not Quantified Adult (>18 years old)Both
    Colorectal cancer
    FecesDetected but not Quantified Adult (>18 years old)BothColorectal Cancer details
    UrineDetected and Quantified7.04 +/- 1.57 umol/mmol creatinineAdult (>18 years old)BothCanavan disease details
    UrineDetected but not Quantified Adult (>18 years old)Both
    Colorectal adenoma
    Associated Disorders and Diseases
    Disease References
    Canavan disease
    1. Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, Di Pietro V, Ceccarelli L, Donzelli S, Francis JS, Giardina B: Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem. 2005 Nov;38(11):997-1008. Epub 2005 Sep 1. [PubMed:16139832 ]
    Associated OMIM IDs
    DrugBank IDNot Available
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB023107
    KNApSAcK IDNot Available
    Chemspider ID62926
    KEGG Compound IDC16359
    BioCyc IDCPD-14119
    BiGG IDNot Available
    Wikipedia LinkNot Available
    METLIN ID2821
    PubChem Compound69726
    PDB IDNot Available
    ChEBI ID68441
    Synthesis ReferencePrusse, August. Synthesis of methylated uric acids according to Behrend and Roosen. Ann. (1925), 441 203-15.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. 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 ]
    2. 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 ]
    3. Tateishi T, Asoh M, Yamaguchi A, Yoda T, Okano YJ, Koitabashi Y, Kobayashi S: Developmental changes in urinary elimination of theophylline and its metabolites in pediatric patients. Pediatr Res. 1999 Jan;45(1):66-70. [PubMed:9890610 ]
    4. Nakano K, Assenza SP, Brown PR: Reversed-phase liquid chromatographic investigation of UV-absorbing low-molecular-weight compounds in saliva. J Chromatogr. 1982 Dec 10;233:51-60. [PubMed:7161362 ]
    5. Grygiel JJ, Wing LM, Farkas J, Birkett DJ: Effects of allopurinol on theophylline metabolism and clearance. Clin Pharmacol Ther. 1979 Nov;26(5):660-7. [PubMed:498708 ]
    6. Kilbane AJ, Silbart LK, Manis M, Beitins IZ, Weber WW: Human N-acetylation genotype determination with urinary caffeine metabolites. Clin Pharmacol Ther. 1990 Apr;47(4):470-7. [PubMed:2328555 ]
    7. 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 ]
    8. 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 ]
    9. 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 ]
    10. Miller CA, Slusher LB, Vesell ES: Polymorphism of theophylline metabolism in man. J Clin Invest. 1985 May;75(5):1415-25. [PubMed:4039734 ]


    General function:
    Involved in oxidoreductase activity
    Specific function:
    Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
    Gene Name:
    Uniprot ID:
    Molecular weight:
    1-Methylxanthine + Water + Oxygen → 1-Methyluric acid + Hydrogen peroxidedetails