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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (2) Show 2 proteins XML

Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2023-02-21 17:15:32 UTC

HMDB ID

HMDB0001216

Secondary Accession Numbers

HMDB01216

Metabolite Identification

Common Name

Tetrahydropteridine

Description

Tetrahydrobiopterin 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

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

View in JSmol View NMR Assignments View Stereo Labels

Synonyms

Value	Source
5,6,7,8-Tetrahydropteridine	Kegg
5,6,7,8-Tetrahydro-pteridine	HMDB
H4-Biopterin	HMDB
THP	HMDB
Tetrahydropteridine	ChEBI

Chemical Formula

C₆H₈N₄

Average Molecular Weight

136.1545

Monoisotopic Molecular Weight

136.074896276

IUPAC Name

5,6,7,8-tetrahydropteridine

Traditional Name

5,6,7,8-tetrahydropteridine

CAS Registry Number

10593-78-9

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 Key

IDAICLIJTRXNER-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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Pteridines and derivatives

Sub Class

Not Available

Direct Parent

Pteridines 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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

pteridines (CHEBI:28889 )
a small molecule (5678-TETRAHYDROPTERIDINE )

Ontology

Physiological effect

Not Available

Disposition

Biological location

Cellular substructure

Cytoplasm (HMDB: HMDB0001216)

Organelle

Mitochondrion (HMDB: HMDB0001216)

Source

Endogenous

Endogenous (HMDB: HMDB0001216)

Pheasant (FooDB: FOOD00430)
Squab (FooDB: FOOD00481)
Turkey (FooDB: FOOD00494)
Quail (FooDB: FOOD00541)
Anatidae (FooDB: FOOD00576)
Rock ptarmigan (FooDB: FOOD00597)
Columbidae (Dove, Pigeon) (FooDB: FOOD00610)
Chicken (FooDB: FOOD00329)
Mallard duck (FooDB: FOOD00353)
Emu (FooDB: FOOD00360)
Greylag goose (FooDB: FOOD00368)
Guinea hen (FooDB: FOOD00373)
Ostrich (FooDB: FOOD00422)
Velvet duck (FooDB: FOOD00427)

Lagomorph

Ovis

Sheep (Mutton, Lamb) (FooDB: FOOD00473)

Bovine

Venison

Deer (FooDB: FOOD00524)
Mule deer (FooDB: FOOD00348)
Elk (FooDB: FOOD00359)

Caprae

Domestic goat (FooDB: FOOD00529)

Swine

Domestic pig (FooDB: FOOD00536)
Wild boar (FooDB: FOOD00307)

Equine

Horse (FooDB: FOOD00378)

Process

Not Available

Role

Not Available

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	1.43 g/L	ALOGPS
logP	0.29	ALOGPS
logP	-0.58	ChemAxon
logS	-2	ALOGPS
pKa (Strongest Acidic)	19.35	ChemAxon
pKa (Strongest Basic)	5.42	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	49.84 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	41.45 m³·mol⁻¹	ChemAxon
Polarizability	13.53 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	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]+	127.58	31661259
DarkChem	[M-H]-	124.084	31661259
AllCCS	[M+H]+	129.426	32859911
AllCCS	[M-H]-	126.252	32859911
DeepCCS	[M+H]+	128.971	30932474
DeepCCS	[M-H]-	125.911	30932474
DeepCCS	[M-2H]-	162.983	30932474
DeepCCS	[M+Na]+	137.855	30932474
AllCCS	[M+H]+	129.4	32859911
AllCCS	[M+H-H2O]+	124.6	32859911
AllCCS	[M+NH4]+	133.9	32859911
AllCCS	[M+Na]+	135.2	32859911
AllCCS	[M-H]-	126.3	32859911
AllCCS	[M+Na-2H]-	127.6	32859911
AllCCS	[M+HCOO]-	129.1	32859911

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Tetrahydropteridine	C1CNC2=C(N1)C=NC=N2	2381.6	Standard polar	33892256
Tetrahydropteridine	C1CNC2=C(N1)C=NC=N2	1424.7	Standard non polar	33892256
Tetrahydropteridine	C1CNC2=C(N1)C=NC=N2	1801.4	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Tetrahydropteridine,1TMS,isomer #1	C[Si](C)(C)N1CCNC2=CN=CN=C21	1671.7	Semi standard non polar	33892256
Tetrahydropteridine,1TMS,isomer #1	C[Si](C)(C)N1CCNC2=CN=CN=C21	1551.5	Standard non polar	33892256
Tetrahydropteridine,1TMS,isomer #1	C[Si](C)(C)N1CCNC2=CN=CN=C21	2860.7	Standard polar	33892256
Tetrahydropteridine,1TMS,isomer #2	C[Si](C)(C)N1CCNC2=NC=NC=C21	1657.0	Semi standard non polar	33892256
Tetrahydropteridine,1TMS,isomer #2	C[Si](C)(C)N1CCNC2=NC=NC=C21	1584.3	Standard non polar	33892256
Tetrahydropteridine,1TMS,isomer #2	C[Si](C)(C)N1CCNC2=NC=NC=C21	2600.8	Standard polar	33892256
Tetrahydropteridine,2TMS,isomer #1	C[Si](C)(C)N1CCN([Si](C)(C)C)C2=NC=NC=C21	1618.1	Semi standard non polar	33892256
Tetrahydropteridine,2TMS,isomer #1	C[Si](C)(C)N1CCN([Si](C)(C)C)C2=NC=NC=C21	1750.9	Standard non polar	33892256
Tetrahydropteridine,2TMS,isomer #1	C[Si](C)(C)N1CCN([Si](C)(C)C)C2=NC=NC=C21	2306.9	Standard polar	33892256
Tetrahydropteridine,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N1CCNC2=CN=CN=C21	1941.0	Semi standard non polar	33892256
Tetrahydropteridine,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N1CCNC2=CN=CN=C21	1828.9	Standard non polar	33892256
Tetrahydropteridine,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N1CCNC2=CN=CN=C21	3207.5	Standard polar	33892256
Tetrahydropteridine,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N1CCNC2=NC=NC=C21	1917.8	Semi standard non polar	33892256
Tetrahydropteridine,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N1CCNC2=NC=NC=C21	1881.8	Standard non polar	33892256
Tetrahydropteridine,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)N1CCNC2=NC=NC=C21	2893.2	Standard polar	33892256
Tetrahydropteridine,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N1CCN([Si](C)(C)C(C)(C)C)C2=NC=NC=C21	2067.0	Semi standard non polar	33892256
Tetrahydropteridine,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N1CCN([Si](C)(C)C(C)(C)C)C2=NC=NC=C21	2275.8	Standard non polar	33892256
Tetrahydropteridine,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)N1CCN([Si](C)(C)C(C)(C)C)C2=NC=NC=C21	2634.2	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - Tetrahydropteridine GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-2900000000-f10ca50f06250e5030d3	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Tetrahydropteridine 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
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Positive-QTOF	splash10-000i-0900000000-9a1ed9296c96ac152018	2015-09-15	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Positive-QTOF	splash10-000i-0900000000-63f9acde2a431bff2488	2015-09-15	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Positive-QTOF	splash10-016r-9100000000-9987b7952a5c983f7c8e	2015-09-15	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Negative-QTOF	splash10-000i-0900000000-93507d1f946deac8a074	2015-09-15	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Negative-QTOF	splash10-000i-0900000000-36867a49c6c36342b032	2015-09-15	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Negative-QTOF	splash10-014i-9800000000-c2d528a7546845512953	2015-09-15	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Negative-QTOF	splash10-000i-0900000000-278b0289a2d1c7916e5b	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Negative-QTOF	splash10-000i-0900000000-7f4a76469d170f8d43f9	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Negative-QTOF	splash10-05nf-7900000000-e829877fe8774c9c13f9	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 10V, Positive-QTOF	splash10-000i-0900000000-06cd9080747456c7643d	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 20V, Positive-QTOF	splash10-000i-0900000000-c5f7233447b8e475f5c6	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Tetrahydropteridine 40V, Positive-QTOF	splash10-0006-9500000000-a22ac8b5a57e8c2437f7	2021-09-24	Wishart Lab	View Spectrum

NMR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Predicted 1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-25	Wishart Lab	View Spectrum
Predicted 1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	2021-09-25	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

Biospecimen Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Name	SMPDB/PathBank	KEGG

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

FDB022495

KNApSAcK ID

Not Available

Chemspider ID

151

KEGG Compound ID

C05650

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

6086

PubChem Compound

156

PDB ID

Not Available

ChEBI ID

28889

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Taylor, 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

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 ]
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 ]
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 ]
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

Enzyme Details

1. Dihydropteridine reductase

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

Enzyme Details

2. Inositol-tetrakisphosphate 1-kinase

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

Showing metabocard for Tetrahydropteridine (HMDB0001216)

MOL for HMDB0001216 (Tetrahydropteridine)

3D MOL for HMDB0001216 (Tetrahydropteridine)

3D SDF for HMDB0001216 (Tetrahydropteridine)

3D-SDF for HMDB0001216 (Tetrahydropteridine)

PDB for HMDB0001216 (Tetrahydropteridine)

3D PDB for HMDB0001216 (Tetrahydropteridine)

SMILES for HMDB0001216 (Tetrahydropteridine)

INCHI for HMDB0001216 (Tetrahydropteridine)

Structure for HMDB0001216 (Tetrahydropteridine)

3D Structure for HMDB0001216 (Tetrahydropteridine)

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

NMR Spectra

IR Spectra

Enzymes