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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (28) Show 28 proteins XML

Record Information

Version

5.0

Status

Detected and Quantified

Creation Date

2006-02-22 11:10:26 UTC

Update Date

2023-02-21 17:15:51 UTC

HMDB ID

HMDB0001860

Secondary Accession Numbers

HMDB01860

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

View in JSmol View NMR Assignments View Stereo Labels

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

Chemical Formula

C₇H₈N₄O₂

Average Molecular Weight

180.164

Monoisotopic Molecular Weight

180.06472552

IUPAC Name

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

Traditional Name

paraxanthine

CAS Registry Number

611-59-6

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 )

Ontology

Not Available

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	351 - 352 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct Type	Data Source	CCS Value (Å²)	Reference
[M+H]+	Baker	135.625	30932474
[M-H]-	Not Available	133.24	http://allccs.zhulab.cn/database/detail?ID=AllCCS00000345
[M+H]+	Not Available	135.625	http://allccs.zhulab.cn/database/detail?ID=AllCCS00000345

Predicted Molecular 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

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	140.385	31661259
DarkChem	[M-H]-	137.36	31661259
AllCCS	[M+H]+	138.467	32859911
AllCCS	[M-H]-	136.811	32859911
DeepCCS	[M+H]+	134.442	30932474
DeepCCS	[M-H]-	131.856	30932474
DeepCCS	[M-2H]-	167.813	30932474
DeepCCS	[M+Na]+	143.14	30932474
AllCCS	[M+H]+	138.5	32859911
AllCCS	[M+H-H2O]+	134.2	32859911
AllCCS	[M+NH4]+	142.5	32859911
AllCCS	[M+Na]+	143.6	32859911
AllCCS	[M-H]-	136.8	32859911
AllCCS	[M+Na-2H]-	137.4	32859911
AllCCS	[M+HCOO]-	138.1	32859911

Predicted Retention Times

Underivatized

Chromatographic Method	Retention Time	Reference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.	2.5 minutes	32390414
Predicted by Siyang on May 30, 2022	8.9648 minutes	33406817
Predicted by Siyang using ReTip algorithm on June 8, 2022	1.68 minutes	32390414
AjsUoB = Accucore 150 Amide HILIC with 10mM Ammonium Formate, 0.1% Formic Acid	34.4 seconds	40023050
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid	711.2 seconds	40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid	294.9 seconds	40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid	79.5 seconds	40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid	174.1 seconds	40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	53.3 seconds	40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid	259.5 seconds	40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid	295.5 seconds	40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)	92.0 seconds	40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid	609.5 seconds	40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid	289.2 seconds	40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid	774.2 seconds	40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	197.9 seconds	40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	178.1 seconds	40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate	570.1 seconds	40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA	182.1 seconds	40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water	128.9 seconds	40023050

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Paraxanthine	CN1C=NC2=C1C(=O)N(C)C(=O)N2	2382.3	Standard polar	33892256
Paraxanthine	CN1C=NC2=C1C(=O)N(C)C(=O)N2	1867.7	Standard non polar	33892256
Paraxanthine	CN1C=NC2=C1C(=O)N(C)C(=O)N2	2065.8	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Paraxanthine,1TMS,isomer #1	CN1C(=O)C2=C(N=CN2C)N([Si](C)(C)C)C1=O	1875.3	Semi standard non polar	33892256
Paraxanthine,1TMS,isomer #1	CN1C(=O)C2=C(N=CN2C)N([Si](C)(C)C)C1=O	2088.9	Standard non polar	33892256
Paraxanthine,1TMS,isomer #1	CN1C(=O)C2=C(N=CN2C)N([Si](C)(C)C)C1=O	2612.9	Standard polar	33892256
Paraxanthine,1TBDMS,isomer #1	CN1C(=O)C2=C(N=CN2C)N([Si](C)(C)C(C)(C)C)C1=O	2095.9	Semi standard non polar	33892256
Paraxanthine,1TBDMS,isomer #1	CN1C(=O)C2=C(N=CN2C)N([Si](C)(C)C(C)(C)C)C1=O	2279.3	Standard non polar	33892256
Paraxanthine,1TBDMS,isomer #1	CN1C(=O)C2=C(N=CN2C)N([Si](C)(C)C(C)(C)C)C1=O	2605.4	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental GC-MS	GC-MS Spectrum - Paraxanthine GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000i-2980000000-6ee5dc3100885f205536	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - Paraxanthine GC-EI-TOF (Non-derivatized)	splash10-000i-2980000000-6ee5dc3100885f205536	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Paraxanthine GC-MS (Non-derivatized) - 70eV, Positive	splash10-0uka-3900000000-d979badf45de391835d4	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Paraxanthine GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Quattro_QQQ 10V, Positive-QTOF (Annotated)	splash10-001i-0900000000-2d1aa5f80618f452686c	2012-07-24	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Quattro_QQQ 25V, Positive-QTOF (Annotated)	splash10-00di-0900000000-3326bcbee23b63dcc230	2012-07-24	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Quattro_QQQ 40V, Positive-QTOF (Annotated)	splash10-014l-9000000000-9824aef9dc2f13c24bcc	2012-07-24	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive-QTOF	splash10-00e9-1900000000-9d0dde13bb1ce13e2644	2012-08-31	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative-QTOF	splash10-00fr-0900000000-1aa733a1b7e41b994d8d	2012-08-31	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine LC-ESI-qTof , Positive-QTOF	splash10-00di-1900000000-190ff3302e9f5a37a72f	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine LC-ESI-QTOF , negative-QTOF	splash10-00fr-0900000000-1aa733a1b7e41b994d8d	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Linear Ion Trap , negative-QTOF	splash10-0229-0900000000-729a2bed81ba15260ffa	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Linear Ion Trap , negative-QTOF	splash10-0229-0900000000-18d0a9c63a1dfb683c9b	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine , negative-QTOF	splash10-004i-0900000000-c52421f0ba1f46241853	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine LC-ESI-IT , positive-QTOF	splash10-00di-0900000000-0bd6ed3d764e5a9b374e	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine LC-ESI-QTOF , positive-QTOF	splash10-00e9-1900000000-9d0dde13bb1ce13e2644	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Linear Ion Trap , positive-QTOF	splash10-0w29-0940000000-127f99d8e7324e01eb66	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine Linear Ion Trap , positive-QTOF	splash10-0ik9-0930000000-fe234438cbe3be0b30f6	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine , positive-QTOF	splash10-00di-1900000000-190ff3302e9f5a37a72f	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine , positive-QTOF	splash10-001i-0900000000-d6040ea84fe19d8c5cc6	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine 10V, Positive-QTOF	splash10-001i-0900000000-935e5a47dc1abe7b1196	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine 35V, Positive-QTOF	splash10-00di-3900000000-2f3998477ce19f3ff96f	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Paraxanthine 20V, Positive-QTOF	splash10-00di-4900000000-c89111b73e8a9a163111	2021-09-20	HMDB team, MONA	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Paraxanthine 10V, Positive-QTOF	splash10-001i-0900000000-5e7c398698bb5c16617d	2017-09-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Paraxanthine 20V, Positive-QTOF	splash10-00di-1900000000-522eaddc21ef92e70e62	2017-09-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Paraxanthine 40V, Positive-QTOF	splash10-0005-9200000000-d10a1141c0e21f56ec00	2017-09-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Paraxanthine 10V, Negative-QTOF	splash10-004i-1900000000-bc2d3cb520a4fcb81529	2017-09-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Paraxanthine 20V, Negative-QTOF	splash10-004i-2900000000-e2e2992ce9b1265af790	2017-09-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Paraxanthine 40V, Negative-QTOF	splash10-05am-9300000000-e1aefedceb8692ffe91f	2017-09-01	Wishart Lab	View Spectrum

NMR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Experimental 1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	2012-12-04	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-29	Wishart Lab	View Spectrum
Experimental 2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	2012-12-05	Wishart Lab	View Spectrum

IR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+)	2023-02-03	FELIX lab	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm (predicted from logP)

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Saliva
Urine

Tissue Locations

Kidney
Liver
Placenta
Prostate

Pathways

Name	SMPDB/PathBank	KEGG
Caffeine Metabolism

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected and Quantified	10.0 (0.30-28.0) uM	Adult (>18 years old)	Both	Normal	15529418	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	24740205	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	24801555	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	25762808	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	27543620	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	25037050	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	29808030	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Not Specified	Normal	22727327	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Normal	22308371	details
Urine	Detected and Quantified	2.5 (3.2-4.0) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	15537072	details
Urine	Detected and Quantified	3.44 +/- 2 umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	Analysis of 30 no...	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal adenoma	27510537	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	1.780 +/- 0.641 uM	Adult (>18 years old)	Not Specified	Favorable outcome from traumatic brain injury	17684518	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	0.833 +/- 1.163 uM	Adult (>18 years old)	Male	Traumatic Brain Injury (TBI)	17684518	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	1.200 +/- 1.373 uM	Adult (>18 years old)	Female	Traumatic Brain Injury (TBI)	17684518	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	0.703 +/- 0.230 uM	Adult (>18 years old)	Not Specified	Traumatic brain injury	17684518	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	0.931 +/- 0.221 uM	Adult (>18 years old)	Not Specified	Traumatic brain injury (TBI)	17684518	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal Cancer	27275383	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal cancer	25037050	details
Urine	Detected and Quantified	3.6 (1.8-5.4) umol/mmol creatinine	Adult (>18 years old)	Both	Asthma	15537072	details
Urine	Detected and Quantified	18.676 +/- 26.196 umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	Analysis of 30 no...	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal adenoma	27510537	details

Associated Disorders and Diseases

Disease References

Traumatic brain injury
Sachse KT, Jackson EK, Wisniewski SR, Gillespie DG, Puccio AM, Clark RS, Dixon CE, Kochanek PM: Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans. J Cereb Blood Flow Metab. 2008 Feb;28(2):395-401. Epub 2007 Aug 8. [PubMed:17684518 ]
Head injury
Sachse KT, Jackson EK, Wisniewski SR, Gillespie DG, Puccio AM, Clark RS, Dixon CE, Kochanek PM: Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans. J Cereb Blood Flow Metab. 2008 Feb;28(2):395-401. Epub 2007 Aug 8. [PubMed:17684518 ]
Colorectal cancer
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 ] 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
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
Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work). NA.

Associated OMIM IDs

114500 (Colorectal cancer)
600807 (Asthma)
610247 (Eosinophilic esophagitis)

External Links

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

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Mueller, Christa E.; Deters, Dirk; Dominik, Andreas; Pawlowski, Maciej. Synthesis of paraxanthine and isoparaxanthine analogs (1,7- and 1,9-substituted xanthine derivatives). Synthesis (1998), (10), 1428-1436.

Material Safety Data Sheet (MSDS)

Download (PDF)

General References

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 ]
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. [PubMed:12811361 ]
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. [PubMed:7920690 ]
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. [PubMed:1629311 ]
Horrigan LA, Kelly JP, Connor TJ: Immunomodulatory effects of caffeine: friend or foe? Pharmacol Ther. 2006 Sep;111(3):877-92. Epub 2006 Mar 15. [PubMed:16540173 ]
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. [PubMed:8445222 ]
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. [PubMed:16198659 ]
Blanchard J, Weber CW, Shearer LE: HPLC analysis of methylxanthines in human breast milk. J Chromatogr Sci. 1990 Dec;28(12):640-2. [PubMed:2292610 ]
Delahunty T, Schoendorfer D: Caffeine demethylation monitoring using a transdermal sweat patch. J Anal Toxicol. 1998 Nov-Dec;22(7):596-600. [PubMed:9847011 ]
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. [PubMed:9613939 ]
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. [PubMed:9156694 ]
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. [PubMed:10839467 ]
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. [PubMed:1576327 ]
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. [PubMed:3998024 ]
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. [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. [PubMed:10546928 ]
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 ]

Only showing the first 10 proteins. There are 28 proteins in total.

Show all enzymes and transporters

Enzymes

Enzyme Details

1. Arylamine N-acetyltransferase 1

General function:: Involved in acetyltransferase activity
Specific function:: Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.
Gene Name:: NAT1
Uniprot ID:: P18440
Molecular weight:: 33898.445

Reactions

Paraxanthine → 5-Acetylamino-6-formylamino-3-methyluracil	details

Enzyme Details

2. Arylamine N-acetyltransferase 2

General function:: Involved in acetyltransferase activity
Specific function:: Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.
Gene Name:: NAT2
Uniprot ID:: P11245
Molecular weight:: 33570.245

Reactions

Paraxanthine → 5-Acetylamino-6-formylamino-3-methyluracil	details

Enzyme Details

3. Xanthine dehydrogenase/oxidase

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

Paraxanthine + Oxygen + Water → 1,7-Dimethyluric acid + Hydrogen peroxide	details

Enzyme Details

4. Cytochrome P450 3A4

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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular weight:: 57255.585

Enzyme Details

5. Cytochrome P450 2C9

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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular weight:: 55627.365

Enzyme Details

6. Cytochrome P450 2C19

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:: CYP2C19
Uniprot ID:: P33261
Molecular weight:: 55944.565

Enzyme Details

7. Cytochrome P450 2E1

General function:: Involved in monooxygenase activity
Specific function:: Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:: CYP2E1
Uniprot ID:: P05181
Molecular weight:: 56848.42

Enzyme Details

8. Cytochrome P450 3A43

General function:: Involved in monooxygenase activity
Specific function:: Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name:: CYP3A43
Uniprot ID:: Q9HB55
Molecular weight:: 57756.285

Enzyme Details

9. Cytochrome P450 1B1

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. Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development.
Gene Name:: CYP1B1
Uniprot ID:: Q16678
Molecular weight:: 60845.33

Enzyme Details

10. Cytochrome P450 2C18

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.
Gene Name:: CYP2C18
Uniprot ID:: P33260
Molecular weight:: 55710.075

Only showing the first 10 proteins. There are 28 proteins in total.

Show all enzymes and transporters

Showing metabocard for Paraxanthine (HMDB0001860)

MOL for HMDB0001860 (Paraxanthine)

3D MOL for HMDB0001860 (Paraxanthine)

3D SDF for HMDB0001860 (Paraxanthine)

3D-SDF for HMDB0001860 (Paraxanthine)

PDB for HMDB0001860 (Paraxanthine)

3D PDB for HMDB0001860 (Paraxanthine)

SMILES for HMDB0001860 (Paraxanthine)

INCHI for HMDB0001860 (Paraxanthine)

Structure for HMDB0001860 (Paraxanthine)

3D Structure for HMDB0001860 (Paraxanthine)

Experimental Collision Cross Sections

Predicted Collision Cross Sections

Predicted Retention Times

Underivatized

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

NMR Spectra

IR Spectra

Enzymes

Reactions

Reactions

Reactions