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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2023-02-21 17:15:32 UTC
HMDB IDHMDB0001216
Secondary Accession Numbers
  • HMDB01216
Metabolite Identification
Common NameTetrahydropteridine
DescriptionTetrahydrobiopterin serves well-characterized cofactor functions for hydroxylating aromatic amino acids and ether lipids and for formation of nitric oxide (NO) from L-arginine. Formation of NO involves two cycles of oxidation of Tetrahydrobiopterin to its radical with subsequent rehydroxylation into Tetrahydrobiopterin, one for reduction of the heme-bound arginine-Fe(II)O2 complex of NO synthase (NOS), the other for reduction of the N-hydroxy-L-arginine-Fe(II)O2 complex. Tetrahydrobiopterin-dependent glyceryl ether monooxygenase (EC 1.14.16.5) is found not only in liver and the gastrointestinal tract but also in brain and other organs (this enzyme plays an essential role in conjugation with the cleavage enzyme in the regulation of cellular levels of -alkyl moieties in glycerolipids). Tetrahydrobiopterin is essential for the enzymatic reaction of tyrosine 3-monooxygenase (EC 1.14.16.2) for the first step in the biosynthesis of catecholamines such as norepinephrine, epinephrine and dopamine. Limited Tetrahydrobiopterin availability not only decreases formation of NO but also causes NOS-derived superoxide/hydrogen peroxide production leading to formation of peroxynitrite as well as S-nitrosoglutathione. As a consequence of its oxygen-activating potential, Tetrahydrobiopterin is also subject to autoxidation in a free radical chain reaction in leading to formation of superoxide and finally to hydrogen peroxide. On the other hand, Tetrahydrobiopterin, like other H4-pterins, can scavenge reactive oxygen species and peroxynitrite. Thus, Tetrahydrobiopterin may have opposing effects in various biological systems depending on whether its cofactor roles outweigh its chemical reactivity or vice versa. Sepiapterin reductase (EC 1.1.1.153) catalyzes the reduction of tetrahydro-sepiapterin to tetrahydrobiopterin -the terminal step in this biosynthetic pathway for tetrahydrobiopterin. This reaction is N-acetyl-serotonin-sensitive and can completely inhibit tetrahydrobiopterin synthesis. (PMID: 3881214 , 17303893 , 3756924 , 15223071 ).
Structure
Data?1676999732
Synonyms
ValueSource
5,6,7,8-TetrahydropteridineKegg
5,6,7,8-Tetrahydro-pteridineHMDB
H4-BiopterinHMDB
THPHMDB
TetrahydropteridineChEBI
Chemical FormulaC6H8N4
Average Molecular Weight136.1545
Monoisotopic Molecular Weight136.074896276
IUPAC Name5,6,7,8-tetrahydropteridine
Traditional Name5,6,7,8-tetrahydropteridine
CAS Registry Number10593-78-9
SMILES
C1CNC2=C(N1)C=NC=N2
InChI Identifier
InChI=1S/C6H8N4/c1-2-9-6-5(8-1)3-7-4-10-6/h3-4,8H,1-2H2,(H,7,9,10)
InChI KeyIDAICLIJTRXNER-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as pteridines and derivatives. These are polycyclic aromatic compounds containing a pteridine moiety, which consists of a pyrimidine fused to a pyrazine ring to form pyrimido(4,5-b)pyrazine.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassNot Available
Direct ParentPteridines and derivatives
Alternative Parents
Substituents
  • Pteridine
  • Secondary aliphatic/aromatic amine
  • Imidolactam
  • Pyrimidine
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility1.43 g/LALOGPS
logP0.29ALOGPS
logP-0.58ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)19.35ChemAxon
pKa (Strongest Basic)5.42ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.84 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity41.45 m³·mol⁻¹ChemAxon
Polarizability13.53 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+127.5831661259
DarkChem[M-H]-124.08431661259
AllCCS[M+H]+129.42632859911
AllCCS[M-H]-126.25232859911
DeepCCS[M+H]+128.97130932474
DeepCCS[M-H]-125.91130932474
DeepCCS[M-2H]-162.98330932474
DeepCCS[M+Na]+137.85530932474
AllCCS[M+H]+129.432859911
AllCCS[M+H-H2O]+124.632859911
AllCCS[M+NH4]+133.932859911
AllCCS[M+Na]+135.232859911
AllCCS[M-H]-126.332859911
AllCCS[M+Na-2H]-127.632859911
AllCCS[M+HCOO]-129.132859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
TetrahydropteridineC1CNC2=C(N1)C=NC=N22381.6Standard polar33892256
TetrahydropteridineC1CNC2=C(N1)C=NC=N21424.7Standard non polar33892256
TetrahydropteridineC1CNC2=C(N1)C=NC=N21801.4Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Tetrahydropteridine,1TMS,isomer #1C[Si](C)(C)N1CCNC2=CN=CN=C211671.7Semi standard non polar33892256
Tetrahydropteridine,1TMS,isomer #1C[Si](C)(C)N1CCNC2=CN=CN=C211551.5Standard non polar33892256
Tetrahydropteridine,1TMS,isomer #1C[Si](C)(C)N1CCNC2=CN=CN=C212860.7Standard polar33892256
Tetrahydropteridine,1TMS,isomer #2C[Si](C)(C)N1CCNC2=NC=NC=C211657.0Semi standard non polar33892256
Tetrahydropteridine,1TMS,isomer #2C[Si](C)(C)N1CCNC2=NC=NC=C211584.3Standard non polar33892256
Tetrahydropteridine,1TMS,isomer #2C[Si](C)(C)N1CCNC2=NC=NC=C212600.8Standard polar33892256
Tetrahydropteridine,2TMS,isomer #1C[Si](C)(C)N1CCN([Si](C)(C)C)C2=NC=NC=C211618.1Semi standard non polar33892256
Tetrahydropteridine,2TMS,isomer #1C[Si](C)(C)N1CCN([Si](C)(C)C)C2=NC=NC=C211750.9Standard non polar33892256
Tetrahydropteridine,2TMS,isomer #1C[Si](C)(C)N1CCN([Si](C)(C)C)C2=NC=NC=C212306.9Standard polar33892256
Tetrahydropteridine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCNC2=CN=CN=C211941.0Semi standard non polar33892256
Tetrahydropteridine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCNC2=CN=CN=C211828.9Standard non polar33892256
Tetrahydropteridine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCNC2=CN=CN=C213207.5Standard polar33892256
Tetrahydropteridine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1CCNC2=NC=NC=C211917.8Semi standard non polar33892256
Tetrahydropteridine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1CCNC2=NC=NC=C211881.8Standard non polar33892256
Tetrahydropteridine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N1CCNC2=NC=NC=C212893.2Standard polar33892256
Tetrahydropteridine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN([Si](C)(C)C(C)(C)C)C2=NC=NC=C212067.0Semi standard non polar33892256
Tetrahydropteridine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN([Si](C)(C)C(C)(C)C)C2=NC=NC=C212275.8Standard non polar33892256
Tetrahydropteridine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N1CCN([Si](C)(C)C(C)(C)C)C2=NC=NC=C212634.2Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Tetrahydropteridine GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-2900000000-f10ca50f06250e5030d32017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Tetrahydropteridine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Positive-QTOFsplash10-000i-0900000000-9a1ed9296c96ac1520182015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Positive-QTOFsplash10-000i-0900000000-63f9acde2a431bff24882015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Positive-QTOFsplash10-016r-9100000000-9987b7952a5c983f7c8e2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Negative-QTOFsplash10-000i-0900000000-93507d1f946deac8a0742015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Negative-QTOFsplash10-000i-0900000000-36867a49c6c36342b0322015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Negative-QTOFsplash10-014i-9800000000-c2d528a75468455129532015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Negative-QTOFsplash10-000i-0900000000-278b0289a2d1c7916e5b2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Negative-QTOFsplash10-000i-0900000000-7f4a76469d170f8d43f92021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Negative-QTOFsplash10-05nf-7900000000-e829877fe8774c9c13f92021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Positive-QTOFsplash10-000i-0900000000-06cd9080747456c7643d2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Positive-QTOFsplash10-000i-0900000000-c5f7233447b8e475f5c62021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Positive-QTOFsplash10-0006-9500000000-a22ac8b5a57e8c2437f72021-09-24Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted 1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum

IR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted IR SpectrumIR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-)2023-02-03FELIX labView Spectrum
Predicted IR SpectrumIR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+)2023-02-03FELIX labView Spectrum
Predicted IR SpectrumIR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+)2023-02-03FELIX labView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen LocationsNot Available
Tissue LocationsNot Available
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022495
KNApSAcK IDNot Available
Chemspider ID151
KEGG Compound IDC05650
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID6086
PubChem Compound156
PDB IDNot Available
ChEBI ID28889
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceTaylor, E. C., Jr.; Carbon, John A.; Garland, Robert B.; Hoff, Dale R.; Howell, Charles F.; Sherman, Wm. R. Recent developments in pteridine synthesis. Ciba Foundation Symposium, Chem. and Biol. Pteridines (1954), 104-20.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Rao GN, Cotlier E: The enzymatic activities of GTP cyclohydrolase, sepiapterin reductase, dihydropteridine reductase and dihydrofolate reductase; and tetrahydrobiopterin content in mammalian ocular tissues and in human senile cataracts. Comp Biochem Physiol B. 1985;80(1):61-6. [PubMed:3881214 ]
  2. Werner ER, Hermetter A, Prast H, Golderer G, Werner-Felmayer G: Widespread occurrence of glyceryl ether monooxygenase activity in rat tissues detected by a novel assay. J Lipid Res. 2007 Jun;48(6):1422-7. Epub 2007 Feb 15. [PubMed:17303893 ]
  3. Hoffman DR, Hoffman LH, Snyder F: Cytotoxicity and metabolism of alkyl phospholipid analogues in neoplastic cells. Cancer Res. 1986 Nov;46(11):5803-9. [PubMed:3756924 ]
  4. Thoeni G, Werner ER, Werner-Felmayer G: Tetrahydropteridines suppress gene expression and induce apoptosis of activated RAW264.7 cells via formation of hydrogen peroxide. Free Radic Biol Med. 2004 Aug 1;37(3):375-85. [PubMed:15223071 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases.
Gene Name:
QDPR
Uniprot ID:
P09417
Molecular weight:
25789.295
General function:
Involved in catalytic activity
Specific function:
Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain.
Gene Name:
ITPK1
Uniprot ID:
Q13572
Molecular weight:
45620.645