| 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 |
|
| 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 |
Download:
MOL |
SDF |
SMILES |
InChI
Display:
2D Structure |
3D Structure
|
| Synonyms |
- (1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol
- 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
- 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-Pteridinone
- 5,6,7,8-Erythro-tetrahydrobiopterin
- 5,6,7,8-Tetra-H-biopterin
- 5,6,7,8-Tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone
- 5,6,7,8-Tetrahydrobiopterin
- L-Erythro-2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinon
- Tetra-H-biopterin
- Tetra-hydro-biopterin
- 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)
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| 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 |
|
| Biofunction |
- Component of Phenylalanine, tyrosine and tryptophan biosynthesis
- Component of Tryptophan metabolism
- Component of Tyrosine metabolism
- Enzyme co-factor
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| Application |
Not Available |
| Cellular locations |
|
| 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 |
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| Predicted Properties |
|
| Spectra |
|
Not Available
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| Biological Properties |
| Cellular Locations |
|
| Biofluid Locations |
- Blood
- Cerebrospinal Fluid (CSF)
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| Tissue Location |
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| Pathways |
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| Normal Concentrations |
|
| Blood |
Detected and Quantified |
|
0.0093 +/- 0.0005 uM |
Adult (>18 years old) |
Both |
Normal |
Not Available |
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| Abnormal Concentrations |
|
| Blood |
Detected and Quantified |
|
0.16 (0.0-5.8) uM |
Adult (>18 years old) |
Both |
Septic shock |
Without renal failure, measured in plasma
|
| Blood |
Detected and Quantified |
|
1.2 (0.8-14.9) uM |
Adult (>18 years old) |
Both |
Septic shock |
With renal failure, measured in plasma
|
| Blood |
Detected and Quantified |
|
0.0044 +/- 0.0007 uM |
Adult (>18 years old) |
Both |
Myocardial infarction |
In plasma, acute myocardial infarction
|
| Cerebrospinal Fluid (CSF) |
Detected and Quantified |
|
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
|
| 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
|
| 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
|
|
| Associated OMIM IDs |
None |
| External Links |
| 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  |
| KEGG Compound ID |
C00272  |
| BioCyc ID |
TETRA-H-BIOPTERIN  |
| BiGG ID |
34464  |
| Wikipedia Link |
Tetrahydrobiopterin  |
| NuGOwiki Link |
HMDB00027  |
| Metagene Link |
HMDB00027  |
| METLIN ID |
5098  |
| PubChem Compound |
1125  |
| PDB ID |
1DF1  |
| ChEBI ID |
15372  |
| 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 |
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
|
| Enzymes |
| Name: |
Tyrosinase
|
| Reactions: |
- L-tyrosine + L-dopa + O2 = L-dopa + dopaquinone + H2O [RN:R02078]
|
| Gene Name: |
TYR |
| Uniprot ID: |
P14679  |
| 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  |
| 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  |
| 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  |
| 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  |
| 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  |
| 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  |
| 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  |
| 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  |
| Protein Sequence: |
FASTA |
| Gene Sequence: |
FASTA |
|
|
|