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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2006-05-22 15:12:32 UTC
Update Date2021-09-07 16:45:34 UTC
HMDB IDHMDB0003099
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 ).
Structure
Data?1582752262
Synonyms
ValueSource
1-MethylateGenerator
1-Methylic acidGenerator
1-MethylurateHMDB
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
SMILES
CN1C(=O)NC2=C(NC(=O)N2)C1=O
InChI Identifier
InChI=1S/C6H6N4O3/c1-10-4(11)2-3(9-6(10)13)8-5(12)7-2/h1H3,(H,9,13)(H2,7,8,12)
InChI KeyQFDRTQONISXGJA-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 PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility5 mg/mLNot Available
LogP-0.57GASPARI,F & BONATI,M (1987)
Predicted Properties
PropertyValueSource
Water Solubility3.23 g/LALOGPS
logP-1.2ALOGPS
logP-1.3ChemAxon
logS-1.8ALOGPS
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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0far-2900000000-7c88ba8c892ca82634732017-09-01View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0far-2900000000-7c88ba8c892ca82634732021-09-05View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-0900000000-f2e42cd67ce1106bed632012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-0900000000-9fd2304504c5787dc2552012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-9000000000-6069b457c0c038edb8df2012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0006-0900000000-f47eba015e7f8d9f21a72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 4V, negativesplash10-001i-0900000000-26da10b11bacabae0d002020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 5V, negativesplash10-001i-0900000000-dceee0216914a6ad03492020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 6V, negativesplash10-001r-0900000000-cb9d81f2cc810b6a1bf62020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 8V, negativesplash10-0019-2900000000-79ddb513e243e4fd10542020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 10V, negativesplash10-001a-7900000000-aeb7c72625ab71bbfcb32020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 12V, negativesplash10-000i-0900000000-72f91c756d76768ecc232020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 12V, negativesplash10-004i-9000000000-0ae8d2338f48c17984cd2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 12V, negativesplash10-001i-9400000000-943dd572fd686e87913d2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 1V, negativesplash10-03di-0109000000-cf0f38f1f9c792f0404d2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 1V, negativesplash10-03di-0309000000-9a8aaf68c144b67fbc6e2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 2V, negativesplash10-01q9-0905000000-d40f59a74d4b8cc4e1d62020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 3V, negativesplash10-001i-0901000000-265af2cad1ab697d32492020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 3V, negativesplash10-001i-0900000000-2b4e4dd83c0bad2269ae2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 4V, negativesplash10-001i-0900000000-c37839583f5e4e15cc462020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 9V, negativesplash10-001i-0900000000-6254efb7ddc081f6fd0c2020-07-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0900000000-9fb7b528d968cab88bd32017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0059-1900000000-eb2d1569b5bdfeef979a2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000w-9300000000-065aa3463c121bf313122017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1900000000-62dd716e79c8fa6f5ee02017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-3900000000-bf85a8ad5b7719f36aba2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-7db60439b29417bbbe0d2017-09-01View Spectrum

NMR

Spectrum TypeDescriptionDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, 5%_DMSO, experimental)2012-12-05View Spectrum
2D NMR[1H, 13C] NMR Spectrum (2D, 600 MHz, 5%_DMSO, predicted)2012-12-05View Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Amniotic Fluid
  • Blood
  • Feces
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Amniotic FluidDetected and Quantified0.51 +/- 0.044 uMAdult (>18 years old)BothNormal details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
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 but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
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
BiospecimenStatusValueAgeSexConditionReferenceDetails
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 Quantified7.04 +/- 1.57 umol/mmol creatinineAdult (>18 years old)BothCanavan disease details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal adenoma
details
Associated Disorders and Diseases
Disease References
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 ]
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
FooDB 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
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000410
References
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. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  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. 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 ]
  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 ]

Enzymes

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:
XDH
Uniprot ID:
P47989
Molecular weight:
146422.99
Reactions
1-Methylxanthine + Water + Oxygen → 1-Methyluric acid + Hydrogen peroxidedetails