MiMeDB: Showing metabocard for Paraxanthine (MMDBc0000394)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:36:47 UTC

Update Date

2024-10-17 15:29:10 UTC

Metabolite ID

MMDBc0000394

Metabolite Identification

Common Name

Paraxanthine

Description

Paraxanthine, also known as p-xanthine, 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. Paraxanthine exists in all living organisms, ranging from bacteria to humans. Within humans, paraxanthine participates in a number of enzymatic reactions. In particular, paraxanthine and formaldehyde can be biosynthesized from caffeine; which is catalyzed by the enzyme cytochrome P450 1A2. In addition, paraxanthine and acetyl-CoA can be converted into 5-acetylamino-6-formylamino-3-methyluracil through its interaction with the enzyme arylamine N-acetyltransferase 2. In humans, paraxanthine is involved in caffeine metabolism.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HEADER    PROTEIN                                 04-SEP-20   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   04-SEP-20         0                                  
HETATM    1  C   UNK     0      23.384 -29.583   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0      17.442 -30.754   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0      23.813 -32.294   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0      21.443 -31.524   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0      21.443 -33.064   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0      20.110 -30.754   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0      18.776 -33.064   0.000  0.00  0.00           C+0
HETATM    8  N   UNK     0      22.908 -33.540   0.000  0.00  0.00           N+0
HETATM    9  N   UNK     0      20.110 -33.834   0.000  0.00  0.00           N+0
HETATM   10  N   UNK     0      22.908 -31.048   0.000  0.00  0.00           N+0
HETATM   11  N   UNK     0      18.776 -31.524   0.000  0.00  0.00           N+0
HETATM   12  O   UNK     0      20.110 -29.214   0.000  0.00  0.00           O+0
HETATM   13  O   UNK     0      17.442 -33.834   0.000  0.00  0.00           O+0
CONECT    1   10                                                            
CONECT    2   11                                                            
CONECT    3   10    8                                                       
CONECT    4    5   10    6                                                  
CONECT    5    4    8    9                                                  
CONECT    6    4   12   11                                                  
CONECT    7   11   13    9                                                  
CONECT    8    3    5                                                       
CONECT    9    5    7                                                       
CONECT   10    1    3    4                                                  
CONECT   11    2    6    7                                                  
CONECT   12    6                                                            
CONECT   13    7                                                            
MASTER        0    0    0    0    0    0    0    0   13    0   28    0
END

Synonyms

Value	Source
3,7-Dihydro-1,7-dimethyl-1H-purine-2,6-dione	ChEBI
p-Xanthine	ChEBI
1,7-Dimethyl-xanthine	HMDB
1,7-Dimethylxanthine	HMDB, MeSH

Molecular Formula

C₇H₈N₄O₂

Average Mass

180.164

Monoisotopic Mass

180.06472552

IUPAC Name

1,7-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Traditional Name

paraxanthine

CAS Registry Number

Not Available

SMILES

CN1C=NC2=C1C(=O)N(C)C(=O)N2

InChI Identifier

InChI=1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)11(2)7(13)9-5/h3H,1-2H3,(H,9,13)

InChI Key

QUNWUDVFRNGTCO-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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Imidazopyrimidines

Sub Class

Purines and purine derivatives

Direct Parent

Xanthines

Alternative Parents

Substituents

Xanthine
6-oxopurine
Purinone
Alkaloid or derivatives
Pyrimidone
Hydroxypyrimidine
N-substituted imidazole
Pyrimidine
Imidazole
Azole
Heteroaromatic compound
Lactam
Azacycle
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organic oxygen compound
Organooxygen compound
Organonitrogen compound
Organic nitrogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

dimethylxanthine (CHEBI:25858 )
Purine alkaloids (C13747 )
a small molecule (1-7-DIMETHYLXANTHINE )

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Property	Value	Source
Water Solubility	9.13 g/L	ALOGPS
logP	-0.63	ALOGPS
logP	0.24	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Acidic)	10.76	ChemAxon
pKa (Strongest Basic)	-0.87	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	67.23 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	46.72 m³·mol⁻¹	ChemAxon
Polarizability	16.87 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Not Available

Biological Properties

Cellular Locations

Cytoplasm

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Kidney
Liver
Placenta
Prostate
Saliva
Urine

Tissue Locations

Kidney
Liver
Placenta
Prostate

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0191696	Arylamine N-acetyltransferase 1	Enzyme	P18440	Homo sapiens
MMDBp0191697	Arylamine N-acetyltransferase 2	Enzyme	P11245	Homo sapiens
MMDBp0191852	Xanthine dehydrogenase/oxidase	Unknown	P47989	Homo sapiens
MMDBp0192630	Cytochrome P450 3A4	Unknown	P08684	Homo sapiens
MMDBp0192647	Cytochrome P450 2C9	Unknown	P11712	Homo sapiens
MMDBp0192649	Cytochrome P450 2C19	Unknown	P33261	Homo sapiens
MMDBp0193099	Cytochrome P450 2E1	Unknown	P05181	Homo sapiens
MMDBp0193101	Cytochrome P450 3A43	Unknown	Q9HB55	Homo sapiens
MMDBp0193102	Cytochrome P450 1B1	Unknown	Q16678	Homo sapiens
MMDBp0193104	Cytochrome P450 2C18	Unknown	P33260	Homo sapiens
MMDBp0193106	Cytochrome P450 2F1	Unknown	P24903	Homo sapiens
MMDBp0193107	Cytochrome P450 4X1	Unknown	Q8N118	Homo sapiens
MMDBp0193108	Cytochrome P450 2B6	Unknown	P20813	Homo sapiens
MMDBp0193109	Cytochrome P450 3A5	Unknown	P20815	Homo sapiens
MMDBp0193111	Cytochrome P450 2A13	Unknown	Q16696	Homo sapiens
MMDBp0193112	Cytochrome P450 3A7	Unknown	P24462	Homo sapiens
MMDBp0193113	Cytochrome P450 4B1	Unknown	P13584	Homo sapiens
MMDBp0193114	Cytochrome P450 4Z1	Unknown	Q86W10	Homo sapiens
MMDBp0193115	Cytochrome P450 1A2	Unknown	P05177	Homo sapiens
MMDBp0193116	Cytochrome P450 19A1	Unknown	P11511	Homo sapiens
MMDBp0193117	Cytochrome P450 2C8	Unknown	P10632	Homo sapiens
MMDBp0193118	Cytochrome P450 2S1	Unknown	Q96SQ9	Homo sapiens
MMDBp0193120	Cytochrome P450 2J2	Unknown	P51589	Homo sapiens
MMDBp0193121	Cytochrome P450 2A7	Unknown	P20853	Homo sapiens
MMDBp0193122	Cytochrome P450 2A6	Unknown	P11509	Homo sapiens
MMDBp0194156	Arylamine N-acetyltransferase 2	Enzyme	A4Z6T7	Homo sapiens
MMDBp0194192	Cytochrome P450, family 1, subfamily A, polypeptide 1	Enzyme	A0N0X8	Homo sapiens
MMDBp0196019	Cytochrome P450 2D6	Enzyme	Q6NWU0	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference

Health Effects and Bioactivity

Health Outcome/Bioactivity	Evidence Type	Host and Biospecimen	Data Source	Reference
Asthma	Association	Human Urine	HMDB	15537072
Traumatic brain injury	Association	Human Cerebrospinal Fluid (CSF)	HMDB	17684518
Eosinophilic esophagitis	Association	Human Urine	HMDB	Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria/Eubacteria	Firmicutes	3	Human stool; Human ; Human feces; Human mucosa; Human saliva; Human urine; Human sputum	Indirect association between microbiota composition and metabolites measured in host biospecimen
Archaea	Euryarchaeota	1	Human feces; Human	Indirect association between microbiota composition and metabolites measured in host biospecimen
Bacteria/Eubacteria	Proteobacteria	1	Human

Exposure Sources

Other Exposures

Source Type	Data Source	Reference
General Exposome	U.S. Environmental Protection Agency	CompTox
Cosmetics	U.S. Environmental Protection Agency	CompTox
Domestics	U.S. Environmental Protection Agency	CompTox
Water	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Urine	Detected and Quantified	3.6		1.8	5.4	umol/mmol creatinine	Adult (>18 years old)	Both	Asthma	HMDB	15537072
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.703	0.230			uM	Adult (>18 years old)	Not Specified	Traumatic brain injury	HMDB	17684518
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.833	1.163			uM	Adult (>18 years old)	Male	Traumatic Brain Injury (TBI)	HMDB	17684518
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.931	0.221			uM	Adult (>18 years old)	Not Specified	Traumatic brain injury (TBI)	HMDB	17684518
Human Cerebrospinal fluid (csf)	Detected and Quantified	1.200	1.373			uM	Adult (>18 years old)	Female	Traumatic Brain Injury (TBI)	HMDB	17684518
Human Cerebrospinal fluid (csf)	Detected and Quantified	1.780	0.641			uM	Adult (>18 years old)	Not Specified	Favorable outcome from traumatic brain injury	HMDB	17684518
Human Blood	Detected and Quantified	10.0		0.30	28.0	uM	Adult (>18 years old)	Both	Normal	HMDB	15529418
Human Urine	Detected and Quantified	2.5		3.2	4.0	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	15537072
Human Urine	Detected and Quantified	18.676	26.196			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Urine	Detected and Quantified	3.44	2			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Kidney	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Liver	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Placenta	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Prostate	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Not Specified	Normal	HMDB	22727327
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	24740205
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	24801555
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	25762808
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	25037050
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	29808030
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

HMDB0001860

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Not Available

Wikipedia Link

Paraxanthine

METLIN ID

1457

PubChem Compound

4687

PDB ID

Not Available

ChEBI ID

25858

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

Blanchard J, Weber CW, Shearer LE: Methylxanthine levels in breast milk of lactating women of different ethnic and socioeconomic classes. Biopharm Drug Dispos. 1992 Apr;13(3):187-96. doi: 10.1002/bdd.2510130305. [PubMed:1576327 ]
Tanaka E: Simultaneous determination of caffeine and its primary demethylated metabolites in human plasma by high-performance liquid chromatography. J Chromatogr. 1992 Mar 27;575(2):311-4. doi: 10.1016/0378-4347(92)80163-k. [PubMed:1629311 ]
Blanchard J, Weber CW, Shearer LE: HPLC analysis of methylxanthines in human breast milk. J Chromatogr Sci. 1990 Dec;28(12):640-2. doi: 10.1093/chromsci/28.12.640. [PubMed:2292610 ]
Wahllander A, Renner E, Karlaganis G: High-performance liquid chromatographic determination of dimethylxanthine metabolites of caffeine in human plasma. J Chromatogr. 1985 Mar 22;338(2):369-75. doi: 10.1016/0378-4347(85)80107-9. [PubMed:3998024 ]
Fuhr U, Rost KL: Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics. 1994 Jun;4(3):109-16. doi: 10.1097/00008571-199406000-00001. [PubMed:7920690 ]
Holstege A, Kurz M, Weinbeck M, Gerok W: Excretion of caffeine and its primary degradation products into bile. J Hepatol. 1993 Jan;17(1):67-73. doi: 10.1016/s0168-8278(05)80523-9. [PubMed:8445222 ]
Fuhr U, Rost KL, Engelhardt R, Sachs M, Liermann D, Belloc C, Beaune P, Janezic S, Grant D, Meyer UA, Staib AH: Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations. Pharmacogenetics. 1996 Apr;6(2):159-76. doi: 10.1097/00008571-199604000-00003. [PubMed:9156694 ]
Holland DT, Godfredsen KA, Page T, Connor JD: Simple high-performance liquid chromatography method for the simultaneous determination of serum caffeine and paraxanthine following rapid sample preparation. J Chromatogr B Biomed Sci Appl. 1998 Apr 10;707(1-2):105-10. doi: 10.1016/s0378-4347(97)00590-2. [PubMed:9613939 ]
Delahunty T, Schoendorfer D: Caffeine demethylation monitoring using a transdermal sweat patch. J Anal Toxicol. 1998 Nov-Dec;22(7):596-600. doi: 10.1093/jat/22.7.596. [PubMed:9847011 ]
Koch JP, ten Tusscher GW, Koppe JG, Guchelaar HJ: Validation of a high-performance liquid chromatography assay for quantification of caffeine and paraxanthine in human serum in the context of CYP1A2 phenotyping. Biomed Chromatogr. 1999 Jun;13(4):309-14. doi: 10.1002/(SICI)1099-0801(199906)13:4<309::AID-BMC881>3.0.CO;2-J. [PubMed:10416066 ]
Sachse C, Ruschen S, Dettling M, Schley J, Bauer S, Muller-Oerlinghausen B, Roots I, Brockmoller J: Flavin monooxygenase 3 (FMO3) polymorphism in a white population: allele frequencies, mutation linkage, and functional effects on clozapine and caffeine metabolism. Clin Pharmacol Ther. 1999 Oct;66(4):431-8. doi: 10.1053/cp.1999.v66.a102203. [PubMed:10546928 ]
Zaigler M, Rietbrock S, Szymanski J, Dericks-Tan JS, Staib AH, Fuhr U: Variation of CYP1A2-dependent caffeine metabolism during menstrual cycle in healthy women. Int J Clin Pharmacol Ther. 2000 May;38(5):235-44. doi: 10.5414/cpp38235. [PubMed:10839467 ]
Christensen M, Andersson K, Dalen P, Mirghani RA, Muirhead GJ, Nordmark A, Tybring G, Wahlberg A, Yasar U, Bertilsson L: The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther. 2003 Jun;73(6):517-28. doi: 10.1016/S0009-9236(03)00050-X. [PubMed:12811361 ]
Granfors MT, Backman JT, Laitila J, Neuvonen PJ: Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2. Clin Pharmacol Ther. 2005 Oct;78(4):400-11. doi: 10.1016/j.clpt.2005.06.009. [PubMed:16198659 ]
Horrigan LA, Kelly JP, Connor TJ: Immunomodulatory effects of caffeine: friend or foe? Pharmacol Ther. 2006 Sep;111(3):877-92. doi: 10.1016/j.pharmthera.2006.02.002. Epub 2006 Mar 15. [PubMed:16540173 ]
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 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Showing metabocard for Paraxanthine (MMDBc0000394)

MOL for #<Metabolite:0x00007f92184324c8>

3D MOL for #<Metabolite:0x00007f92184324c8>

3D SDF for #<Metabolite:0x00007f92184324c8>

3D-SDF for #<Metabolite:0x00007f92184324c8>

PDB for #<Metabolite:0x00007f92184324c8>

3D PDB for #<Metabolite:0x00007f92184324c8>

SMILES for #<Metabolite:0x00007f92184324c8>

INCHI for #<Metabolite:0x00007f92184324c8>

Structure for #<Metabolite:0x00007f92184324c8>

3D Structure for #<Metabolite:0x00007f92184324c8>