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Human Metabolome Database Version 3.5

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Showing metabocard for Tetrahydrobiopterin (HMDB00027)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:07:47 -0700
HMDB ID HMDB00027
Secondary Accession Numbers
  • HMDB02154
Metabolite Identification
Common Name Tetrahydrobiopterin
Description Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. In fact it is used by all three human nitric-oxide synthases (NOS) eNOS, nNOS, and iNOS as well as the enzyme glyceryl-ether monooxygenase. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase. Specifically, tetrahydrobiopterin is a cofactor for tryptophan 5-hydroxylase 1, tyrosine 3-monooxygenase, and phenylalanine hydroxylase all of which are essential for the formation of the neurotransmitters dopamine, noradrenaline and adrenaline. Tetrahydrobiopterin has been proposed to be involved in promotion of neurotransmitter release in the brain and the regulation of human melanogenesis. A defect in BH4 production and/or a defect in the enzyme dihydropteridine reductase (DHPR) causes phenylketonuria type IV, as well as dopa-responsive dystonias. BH4 is also implicated in Parkinson's disease, Alzheimer's disease and depression. Tetrahydrobiopterin is present in probably every cell or tissue of higher animals. On the other hand, most bacteria, fungi and plants do not synthesize tetrahydrobiopterin. -- Wikipedia.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. (1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol
  2. 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1H)-5,6,7,8-Tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone
  3. 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-Pteridinone
  4. 5,6,7,8-Erythro-tetrahydrobiopterin
  5. 5,6,7,8-Tetra-H-biopterin
  6. 5,6,7,8-Tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone
  7. 5,6,7,8-Tetrahydrobiopterin
  8. L-Erythro-2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinon
  9. Tetra-H-biopterin
  10. Tetra-hydro-biopterin
  11. Tetrahydrobiopterin
Chemical Formula C9H15N5O3
Average Molecular Weight 241.2471
Monoisotopic Molecular Weight 241.117489371
IUPAC Name 2-amino-6-(1,2-dihydroxypropyl)-3,4,5,6,7,8-hexahydropteridin-4-one
Traditional IUPAC Name BH4
CAS Registry Number 17528-72-2
SMILES CC(O)C(O)C1CNC2=C(N1)C(=O)NC(N)=N2
InChI Identifier InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)
InChI Key FNKQXYHWGSIFBK-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Heteropolycyclic Compounds
Class Pteridines and Derivatives
Sub Class Pterins and Derivatives
Other Descriptors
  • Pterins and Derivatives
  • a biopterin(Cyc)
  • biopterins(ChEBI)
  • tetrahydropterin(ChEBI)
Substituents
  • 1,2 Aminoalcohol
  • 1,2 Diol
  • 1,3 Aminoalcohol
  • Aminopyrimidine
  • Pyrimidine
  • Pyrimidone
  • Secondary Alcohol
Direct Parent Biopterins and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Phenylalanine, tyrosine and tryptophan biosynthesis
  • Component of Tryptophan metabolism
  • Component of Tyrosine metabolism
  • Enzyme co-factor
Application Not Available
Cellular locations
  • Nucleus
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 250 - 255 °C (hydrochloride salt) Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 2.03 g/L ALOGPS
LogP -1.82 ALOGPS
LogP -2.3 ChemAxon
LogS -2.07 ALOGPS
pKa (strongest acidic) 11.12 ChemAxon
pKa (strongest basic) 4.61 ChemAxon
Hydrogen Acceptor Count 7 ChemAxon
Hydrogen Donor Count 6 ChemAxon
Polar Surface Area 132 A2 ChemAxon
Rotatable Bond Count 2 ChemAxon
Refractivity 68.63 ChemAxon
Polarizability 23.53 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Nucleus
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • All Tissues
Pathways
Name SMPDB Link KEGG Link
Pterine Biosynthesis SMP00005 map00790 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
0.0093 +/- 0.0005 uM Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
0.16 (0.0-5.8) uM Adult (>18 years old) Both Septic shock Without renal failure, measured in plasma
Blood Detected and Quantified
Article_icon
1.2 (0.8-14.9) uM Adult (>18 years old) Both Septic shock With renal failure, measured in plasma
Blood Detected and Quantified
Article_icon
0.0044 +/- 0.0007 uM Adult (>18 years old) Both Myocardial infarction In plasma, acute myocardial infarction
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
14400.0 uM Newborn (0-30 days old) Both Seizures Not Available
Associated Disorders and Diseases
Disease References
Epilepsy
  • Cady EB, Lorek A, Penrice J, Reynolds EO, Iles RA, Burns SP, Coutts GA, Cowan FM: Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Med. 1994 Dec;32(6):764-7. Pubmed: 7869898 Link_out
    Septic shock
    • Galley HF, Le Cras AE, Yassen K, Grant IS, Webster NR: Circulating tetrahydrobiopterin concentrations in patients with septic shock. Br J Anaesth. 2001 Apr;86(4):578-80. Pubmed: 11573638 Link_out
      Myocardial infarction
      • Yada T, Kaji S, Akasaka T, Mochizuki S, Ogasawara Y, Tanemoto K, Yoshida K, Kajiya F: Changes of asymmetric dimethylarginine, nitric oxide, tetrahydrobiopterin, and oxidative stress in patients with acute myocardial infarction by medical treatments. Clin Hemorheol Microcirc. 2007;37(3):269-76. Pubmed: 17726257 Link_out
        Associated OMIM IDs None
        DrugBank ID Not Available
        Phenol Explorer Compound ID Not Available
        Phenol Explorer Metabolite ID Not Available
        FoodDB ID FDB021880
        KNApSAcK ID Not Available
        Chemspider ID 1093 Link_out
        KEGG Compound ID C00272 Link_out
        BioCyc ID TETRA-H-BIOPTERIN Link_out
        BiGG ID 34464 Link_out
        Wikipedia Link Tetrahydrobiopterin Link_out
        NuGOwiki Link HMDB00027 Link_out
        Metagene Link HMDB00027 Link_out
        METLIN ID 5098 Link_out
        PubChem Compound 1125 Link_out
        PDB ID 1DF1 Link_out
        ChEBI ID 15372 Link_out
        References
        Synthesis Reference He, Aimin. The function and biosynthesis of tetrahydrobiopterin in nocardia. (2002), 123 pp.
        Material Safety Data Sheet (MSDS) Download (PDF)
        General References
        1. Galley HF, Le Cras AE, Yassen K, Grant IS, Webster NR: Circulating tetrahydrobiopterin concentrations in patients with septic shock. Br J Anaesth. 2001 Apr;86(4):578-80. Pubmed: 11573638 Link_out
        2. Kuhn DM, Geddes TJ: Tetrahydrobiopterin prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide. Mol Pharmacol. 2003 Oct;64(4):946-53. Pubmed: 14500751 Link_out
        3. Takikawa S, Curtius HC, Redweik U, Leimbacher W, Ghisla S: Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver. Eur J Biochem. 1986 Dec 1;161(2):295-302. Pubmed: 3536512 Link_out
        4. Walter R, Kaufmann PA, Buck A, Berthold T, Wyss C, von Schulthess GK, Schaffner A, Schoedon G: Tetrahydrobiopterin increases myocardial blood flow in healthy volunteers: a double-blind, placebo-controlled study. Swiss Med Wkly. 2001 Feb 24;131(7-8):91-4. Pubmed: 11416883 Link_out
        5. Hyland K, Gunasekara RS, Munk-Martin TL, Arnold LA, Engle T: The hph-1 mouse: a model for dominantly inherited GTP-cyclohydrolase deficiency. Ann Neurol. 2003;54 Suppl 6:S46-8. Pubmed: 12891653 Link_out
        6. 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 Link_out
        7. Schallreuter KU, Moore J, Wood JM, Beazley WD, Peters EM, Marles LK, Behrens-Williams SC, Dummer R, Blau N, Thony B: Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes? J Invest Dermatol. 2001 Jan;116(1):167-74. Pubmed: 11168813 Link_out
        8. Dhondt JL, Cotton RG, Danks DM: Liver enzyme activities in hyperphenylalaninaemia due to a defective synthesis of tetrahydrobiopterin. J Inherit Metab Dis. 1985;8(2):47-8. Pubmed: 3939528 Link_out
        9. Sawabe K, Suetake Y, Nakanishi N, Wakasugi KO, Hasegawa H: Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes; direct uptake and indirect uptake mediated by a methotrexate-sensitive process. Mol Genet Metab. 2005 Dec;86 Suppl 1:S133-8. Epub 2005 Sep 13. Pubmed: 16165391 Link_out
        10. Koch R, Moseley KD, Moats R, Yano S, Matalon R, Guttler F: Danger of high-protein dietary supplements to persons with hyperphenylalaninaemia. J Inherit Metab Dis. 2003;26(4):339-42. Pubmed: 12971421 Link_out
        11. Cady EB, Lorek A, Penrice J, Reynolds EO, Iles RA, Burns SP, Coutts GA, Cowan FM: Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Med. 1994 Dec;32(6):764-7. Pubmed: 7869898 Link_out
        12. Matter H, Kumar HS, Fedorov R, Frey A, Kotsonis P, Hartmann E, Frohlich LG, Reif A, Pfleiderer W, Scheurer P, Ghosh DK, Schlichting I, Schmidt HH: Structural analysis of isoform-specific inhibitors targeting the tetrahydrobiopterin binding site of human nitric oxide synthases. J Med Chem. 2005 Jul 28;48(15):4783-92. Pubmed: 16033258 Link_out
        13. 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 Link_out
        14. Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, Shimadzu M, Hyland K, Trugman JM: Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol. 1998 Jul;44(1):10-6. Pubmed: 9667588 Link_out
        15. Kaufman S, Kapatos G, Rizzo WB, Schulman JD, Tamarkin L, Van Loon GR: Tetrahydropterin therapy for hyperphenylalaninemia caused by defective synthesis of tetrahydrobiopterin. Ann Neurol. 1983 Sep;14(3):308-15. Pubmed: 6139056 Link_out
        16. Spaapen LJ, Bakker JA, Velter C, Loots W, Rubio-Gozalbo ME, Forget PP, Dorland L, De Koning TJ, Poll-The BT, Ploos van Amstel HK, Bekhof J, Blau N, Duran M: Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates. J Inherit Metab Dis. 2001 Jun;24(3):352-8. Pubmed: 11486900 Link_out
        Enzymes
        Name: Tyrosinase
        Reactions:
        • L-tyrosine + L-dopa + O2 = L-dopa + dopaquinone + H2O [RN:R02078]
        Gene Name: TYR
        Uniprot ID: P14679 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Tyrosine 3-monooxygenase
        Reactions:
        • L-tyrosine + tetrahydrobiopterin + O2 = 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin [RN:R07212]
        Gene Name: TH
        Uniprot ID: P07101 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Phenylalanine-4-hydroxylase
        Reactions:
        • L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin [RN:R07211]
        Gene Name: PAH
        Uniprot ID: P00439 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: 6-pyruvoyl tetrahydrobiopterin synthase
        Reactions:
        • 7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate [RN:R04286]
        Gene Name: PTS
        Uniprot ID: Q03393 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Sepiapterin reductase
        Reactions:
        • (1) 7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+ [RN:R02975]
        • (2) tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+ [RN:R08208]
        Gene Name: SPR
        Uniprot ID: P35270 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Tryptophan 5-hydroxylase 1
        Reactions:
        • L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin [RN:R07213]
        Gene Name: TPH1
        Uniprot ID: P17752 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Tryptophan 5-hydroxylase 2
        Reactions:
        • L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin [RN:R07213]
        Gene Name: TPH2
        Uniprot ID: Q8IWU9 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Dihydropteridine reductase
        Reactions:
        • a 5,6,7,8-tetrahydropteridine + NAD(P)+ = a 6,7-dihydropteridine + NAD(P)H + H+ [RN:R07354 R07355]
        Gene Name: QDPR
        Uniprot ID: P09417 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Nitric oxide synthase, inducible
        Reactions:
        • L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+ [RN:R00557]
        Gene Name: NOS2
        Uniprot ID: P35228 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Nitric oxide synthase, brain
        Reactions:
        • L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+ [RN:R00557]
        Gene Name: NOS1
        Uniprot ID: P29475 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: Nitric oxide synthase, endothelial
        Reactions:
        • L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+ [RN:R00557]
        Gene Name: NOS3
        Uniprot ID: P29474 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: GTP cyclohydrolase 1
        Reactions:
        • GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate [RN:R00424]
        Gene Name: GCH1
        Uniprot ID: P30793 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: GTP cyclohydrolase 1 feedback regulatory protein
        Reactions:
          Gene Name: GCHFR
          Uniprot ID: P30047 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Pterin-4-alpha-carbinolamine dehydratase
          Reactions:
          • (6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a- hydroxypterin = (6R)-6-(L-erythro-1,2-dihydroxypropyl)-7,8-dihydro-6H-pterin + H2O [RN:R04734]
          Gene Name: PCBD1
          Uniprot ID: P61457 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Calcium-calmodulin independent nitric oxide synthase iNOS protein
          Reactions:
            Gene Name: Not Available
            Uniprot ID: Q9UM94 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA