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
Version4.0
StatusDetected and Quantified
Creation Date2008-10-16 22:20:23 UTC
Update Date2020-11-09 23:18:07 UTC
HMDB IDHMDB0010738
Secondary Accession Numbers
  • HMDB10738
Metabolite Identification
Common Name1-Methylxanthine
Description1-Methylxanthine 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. 1-methylxanthine is the major metabolites of caffeine in the human. 1-Methylxanthine is one of the major metabolites of caffeine in humans. 1-Methylxanthine is an extremely weak basic (essentially neutral) compound (based on its pKa). 1-Methylxanthine exists in all living organisms, ranging from bacteria to humans. Within humans, 1-methylxanthine participates in a number of enzymatic reactions. In particular, 1-methylxanthine and formaldehyde can be biosynthesized from theophylline through its interaction with the enzyme cytochrome P450 1A2. In addition, 1-methylxanthine can be converted into 1-methyluric acid; which is catalyzed by the enzyme xanthine dehydrogenase/oxidase. In humans, 1-methylxanthine is involved in caffeine metabolism.
Structure
Data?1582752867
SynonymsNot Available
Chemical FormulaC6H6N4O2
Average Molecular Weight166.1374
Monoisotopic Molecular Weight166.049075456
IUPAC Name1-methyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
Traditional Name1-methylxanthine
CAS Registry Number6136-37-4
SMILES
CN1C(=O)NC2=C(NC=N2)C1=O
InChI Identifier
InChI=1S/C6H6N4O2/c1-10-5(11)3-4(8-2-7-3)9-6(10)12/h2H,1H3,(H,7,8)(H,9,12)
InChI KeyMVOYJPOZRLFTCP-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 SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility11.7 g/LALOGPS
logP-0.46ALOGPS
logP0.017ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)7.91ChemAxon
pKa (Strongest Basic)-0.72ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.09 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity41.82 m³·mol⁻¹ChemAxon
Polarizability14.8 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, Positivesplash10-0apr-3900000000-88bd492326591e730086Spectrum
LC-MS/MSLC-MS/MS Spectrum - NA , positivesplash10-014i-0900000000-a729acfc9694f20accb0Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 3V, positivesplash10-014i-0900000000-6d707d0f8b77fb6f3fcdSpectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 4V, positivesplash10-014i-0900000000-a55efb1f01a8ca4a2d95Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 4V, positivesplash10-02t9-0900000000-858059d2d9ee8414cafdSpectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 5V, positivesplash10-02t9-0900000000-63a50718538a27464c46Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 6V, positivesplash10-03di-0900000000-a00013c8cdc36103e8a3Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 8V, positivesplash10-03di-2900000000-77efece85a8e1b602d5cSpectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 9V, positivesplash10-08fr-6900000000-0d9cd06c582f1bf23225Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 11V, positivesplash10-0a4i-9300000000-b73bf7301278872b9e26Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 14V, positivesplash10-0a4i-9100000000-c05924743c475bbab05bSpectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 17V, positivesplash10-0a4i-9000000000-c01a620479ccd936f5eaSpectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 11V, positivesplash10-03di-0900000000-9fadde7724e8a2f4bab8Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 11V, positivesplash10-001i-9000000000-5277d916d914013bd114Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 11V, positivesplash10-00di-0900000000-b32aa806de261f5c0e40Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 2V, positivesplash10-03di-1900000000-14f01d07c28c61c92026Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 2V, positivesplash10-03di-1900000000-56b961120be01ee88794Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 3V, positivesplash10-03di-2900000000-a21b7d715ff67be12f30Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 4V, positivesplash10-03di-5900000000-f069376ed73a3dc10f54Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 5V, positivesplash10-0bt9-9500000000-627f0d2416135b20579bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-870901373643f9963bf5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03xr-0900000000-54540cdf9de1abed31f9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-02u0-9400000000-df69b5d77ae7adac9ed5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-1900000000-f6dc4dabad421c556050Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-3900000000-82481c42feeeb1737775Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05mo-9200000000-c5e7b6ee0ee1354a37acSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
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)Both
Normal
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Female
Normal
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal 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 Quantified6.0 (4.0-9.0) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal adenoma
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothColorectal Cancer details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
UrineDetected and Quantified6.0 (4.0-10.0) umol/mmol creatinineAdult (>18 years old)Both
Asthma
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. 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 ]
  3. 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 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB027885
KNApSAcK IDNot Available
Chemspider ID72464
KEGG Compound IDC16358
BioCyc IDCPD-9025
BiGG IDNot Available
Wikipedia LinkXanthine
METLIN IDNot Available
PubChem Compound80220
PDB IDNot Available
ChEBI ID68444
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Sims CR 3rd, Delima LR, Calimaran A, Hester R, Pruett WA: Validating the Physiologic Model HumMod as a Substitute for Clinical Trials Involving Acute Normovolemic Hemodilution. Anesth Analg. 2018 Jan;126(1):93-101. doi: 10.1213/ANE.0000000000002430. [PubMed:28863020 ]

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
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915