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
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:07:48 UTC
HMDB IDHMDB00038
Secondary Accession NumbersNone
Metabolite Identification
Common NameDihydrobiopterin
DescriptionDihydrobiopterin (BH2) is an oxidation product of tetrahydrobiopterin. Tetrahydrobiopterin is a natural occurring cofactor of the aromatic amino acid hydroxylase and is involved in the synthesis of tyrosine and the neurotransmitters dopamine and serotonin. Tetrahydrobiopterin is also essential for nitric oxide synthase catalyzed oxidation of L-arginine to L-citrulline and nitric oxide.
Structure
Thumb
Synonyms
  1. (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-7,8-dihydro-6H-pterin
  2. (S-(R*,S*))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone
  3. 2-Amino-6-((1R,2S)-1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone
  4. 2-Amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone
  5. 6,7-Dihydrobiopterin
  6. 7,8-Dihydro-L-biopterin
  7. 7,8-Dihydrobiopterin
  8. BH2
  9. Dihydrobiopterin
  10. L-Erythro-1-(2-amino-7,8-dihydro-4-hydroxy-6-pteridinyl)-1,2-Propanediol
  11. L-Erythro-7,8-Dihydrobiopterin
  12. L-Erythro-Dihydrobiopterin
  13. L-Erythro-q-Dihydrobiopterin
  14. Quinoid-dihydrobiopterin
  15. Quinonoid dihydrobiopterin
Chemical FormulaC9H13N5O3
Average Molecular Weight239.2312
Monoisotopic Molecular Weight239.101839307
IUPAC Name2-amino-6-(1,2-dihydroxypropyl)-3,4,7,8-tetrahydropteridin-4-one
Traditional IUPAC Name2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-3H-pteridin-4-one
CAS Registry Number6779-87-9
SMILES
CC(O)C(O)C1=NC2=C(NC1)N=C(N)NC2=O
InChI Identifier
InChI=1S/C9H13N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3,6,15-16H,2H2,1H3,(H4,10,11,13,14,17)
InChI KeyFEMXZDUTFRTWPE-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassPteridines and Derivatives
Sub ClassPterins and Derivatives
Other Descriptors
  • Pterins and Derivatives
  • a biopterin(Cyc)
Substituents
  • 1,2 Diol
  • 1,3 Aminoalcohol
  • Aminopyrimidine
  • Imine
  • Pyrimidine
  • Pyrimidone
  • Secondary Alcohol
Direct ParentBiopterins and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Folate biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm
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 Solubility1.63 g/LALOGPS
logP-1.6ALOGPS
logP-1.9ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)10.81ChemAxon
pKa (Strongest Basic)3.67ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area132.33ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity68.31ChemAxon
Polarizability23.04ChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Catecholamine BiosynthesisSMP00012map00350
Pterine BiosynthesisSMP00005map00790
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.006 +/- 0.0003 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0004-0.014 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0635 +/- 0.0041 uMAdult (>18 years old)Both
Kidney disease
details
Associated Disorders and Diseases
Disease References
Kidney disease
  1. Yokoyama K, Tajima M, Yoshida H, Nakayama M, Tokutome G, Sakagami H, Hosoya T: Plasma pteridine concentrations in patients with chronic renal failure. Nephrol Dial Transplant. 2002 Jun;17(6):1032-6. Pubmed: 12032193
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021884
KNApSAcK IDNot Available
Chemspider ID247
KEGG Compound IDC02953
BioCyc IDBIOPTERIN
BiGG IDNot Available
Wikipedia LinkDihydrobiopterin
NuGOwiki LinkHMDB00038
Metagene LinkHMDB00038
METLIN ID5106
PubChem Compound252
PDB ID1DCP
ChEBI ID64277
References
Synthesis ReferenceGal E M. Synthesis and quantitative aspects of dihydrobiopterin control of cerebral serotonin levels. Advances in experimental medicine and biology (1981), 133 197-206.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Bonafe L, Thony B, Penzien JM, Czarnecki B, Blau N: Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet. 2001 Aug;69(2):269-77. Epub 2001 Jul 6. Pubmed: 11443547
  2. Goodwill KE, Sabatier C, Stevens RC: Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. Biochemistry. 1998 Sep 29;37(39):13437-45. Pubmed: 9753429
  3. Leeming RJ, Blair JA, Melikian V, O'Gorman DJ: Biopterin derivatives in human body fluids and tissues. J Clin Pathol. 1976 May;29(5):444-51. Pubmed: 932231
  4. Witteveen CF, Giovanelli J, Kaufman S: Reduction of quinonoid dihydrobiopterin to tetrahydrobiopterin by nitric oxide synthase. J Biol Chem. 1996 Feb 23;271(8):4143-7. Pubmed: 8626754
  5. Niederwieser A, Curtius HC, Bettoni O, Bieri J, Schircks B, Viscontini M, Schaub J: Atypical phenylketonuria caused by 7, 8-dihydrobiopterin synthetase deficiency. Lancet. 1979 Jan 20;1(8108):131-3. Pubmed: 84153
  6. Topal G, Brunet A, Millanvoye E, Boucher JL, Rendu F, Devynck MA, David-Dufilho M: Homocysteine induces oxidative stress by uncoupling of NO synthase activity through reduction of tetrahydrobiopterin. Free Radic Biol Med. 2004 Jun 15;36(12):1532-41. Pubmed: 15182855
  7. Yokoyama K, Tajima M, Yoshida H, Nakayama M, Tokutome G, Sakagami H, Hosoya T: Plasma pteridine concentrations in patients with chronic renal failure. Nephrol Dial Transplant. 2002 Jun;17(6):1032-6. Pubmed: 12032193
  8. Hagedoorn PL, Schmidt PP, Andersson KK, Hagen WR, Flatmark T, Martinez A: The effect of substrate, dihydrobiopterin, and dopamine on the EPR spectroscopic properties and the midpoint potential of the catalytic iron in recombinant human phenylalanine hydroxylase. J Biol Chem. 2001 Jun 22;276(25):22850-6. Epub 2001 Apr 11. Pubmed: 11301319
  9. Howells DW, Hyland K: Direct analysis of tetrahydrobiopterin in cerebrospinal fluid by high-performance liquid chromatography with redox electrochemistry: prevention of autoxidation during storage and analysis. Clin Chim Acta. 1987 Jul 30;167(1):23-30. Pubmed: 3665086
  10. Shinozaki K, Hirayama A, Nishio Y, Yoshida Y, Ohtani T, Okamura T, Masada M, Kikkawa R, Kodama K, Kashiwagi A: Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress. J Am Coll Cardiol. 2001 Dec;38(7):1821-8. Pubmed: 11738280

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
Gene Name:
TYR
Uniprot ID:
P14679
Molecular weight:
60392.69
References
  1. Wood JM, Chavan B, Hafeez I, Schallreuter KU: Regulation of tyrosinase by tetrahydropteridines and H2O2. Biochem Biophys Res Commun. 2004 Dec 24;325(4):1412-7. Pubmed: 15555584
General function:
Involved in monooxygenase activity
Specific function:
Plays an important role in the physiology of adrenergic neurons.
Gene Name:
TH
Uniprot ID:
P07101
Molecular weight:
55611.26
References
  1. Goodwill KE, Sabatier C, Stevens RC: Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. Biochemistry. 1998 Sep 29;37(39):13437-45. Pubmed: 9753429
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
Gene Name:
SPR
Uniprot ID:
P35270
Molecular weight:
28048.13
Reactions
Dihydrobiopterin + NADP → Sepiapterin + NADPHdetails
References
  1. Curtius HC, Heintel D, Ghisla S, Kuster T, Leimbacher W, Niederwieser A: Tetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved. Eur J Biochem. 1985 May 2;148(3):413-9. Pubmed: 3888618
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
TPH1
Uniprot ID:
P17752
Molecular weight:
50984.725
References
  1. Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC: Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry. 2002 Oct 22;41(42):12569-74. Pubmed: 12379098
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 dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
References
  1. Bowers SW, Duch DS: In vivo measurement of dihydrofolate reductase and its inhibition by antifolates. Anal Biochem. 1988 Jul;172(1):169-75. Pubmed: 3189762
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
Gene Name:
NOS1
Uniprot ID:
P29475
Molecular weight:
160969.095
References
  1. Li H, Igarashi J, Jamal J, Yang W, Poulos TL: Structural studies of constitutive nitric oxide synthases with diatomic ligands bound. J Biol Inorg Chem. 2006 Sep;11(6):753-68. Epub 2006 Jun 28. Pubmed: 16804678
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
Gene Name:
NOS3
Uniprot ID:
P29474
Molecular weight:
133273.59
References
  1. Lowe ER, Everett AC, Lee AJ, Lau M, Dunbar AY, Berka V, Tsai AL, Osawa Y: Time-dependent inhibition and tetrahydrobiopterin depletion of endothelial nitric-oxide synthase caused by cigarettes. Drug Metab Dispos. 2005 Jan;33(1):131-8. Epub 2004 Oct 6. Pubmed: 15470159
General function:
Involved in 4-alpha-hydroxytetrahydrobiopterin dehydratase activity
Specific function:
Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity.
Gene Name:
PCBD1
Uniprot ID:
P61457
Molecular weight:
11999.515
Reactions
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin → Dihydrobiopterin + Waterdetails
General function:
Involved in 4-alpha-hydroxytetrahydrobiopterin dehydratase activity
Specific function:
Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2 (By similarity). Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity.
Gene Name:
PCBD2
Uniprot ID:
Q9H0N5
Molecular weight:
14365.325
Reactions
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin → Dihydrobiopterin + Waterdetails
General function:
Not Available
Specific function:
Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids. Ether lipids are essential components of brain membranes.
Gene Name:
AGMO
Uniprot ID:
Q6ZNB7
Molecular weight:
51499.41
Reactions
1-alkyl-sn-glycerol + L-erythro-tetrahydrobiopterin + Oxygen → 1-O-alkyl-sn-glycerol + Dihydrobiopterin + Waterdetails