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Record Information
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2021-09-14 15:15:56 UTC
Secondary Accession Numbers
  • HMDB0000787
  • HMDB0002154
  • HMDB00027
  • HMDB0059658
  • HMDB00787
  • HMDB02154
  • HMDB59658
Metabolite Identification
Common NameTetrahydrobiopterin
DescriptionTetrahydrobiopterin (CAS: 17528-72-2), also known as BH4, is an essential cofactor in the synthesis of neurotransmitters and nitric oxide (PMID: 16946131 ). 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 into tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine into L-dopa by the enzyme tyrosine hydroxylase; and the conversion of tryptophan into 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 the 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 ).
5,6,7,8-erythro-TetrahydrobiopterinMeSH, HMDB
5,6,7,8-tetrahydro-L-ErythrobiopterinMeSH, HMDB
5,6,7,8-Tetrahydrobiopterin, (S-(r*,s*))-isomerMeSH, HMDB
5,6,7,8-TetrahydrodictyopterinMeSH, HMDB
6R-L-erythro-5,6,7,8-TetrahydrobiopterinMeSH, HMDB
D-threo-TetrahydrobiopterinMeSH, HMDB
Phenylalanine hydroxylase cofactorMeSH, HMDB
Sapropterin dihydrochlorideMeSH, HMDB
tetrahydro-6-BiopterinMeSH, HMDB
1-Butanone, 1-(2,4,5-trihydroxyphenyl)MeSH
Chemical FormulaC9H15N5O3
Average Molecular Weight241.2471
Monoisotopic Molecular Weight241.117489371
IUPAC Name(6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-1,4,5,6,7,8-hexahydropteridin-4-one
Traditional Nametetrahydrobiopterin
CAS Registry Number62989-33-7
InChI Identifier
Chemical Taxonomy
Description Belongs to the class of organic compounds known as biopterins and derivatives. These are coenzymes containing a 2-amino-pteridine-4-one derivative. They are mainly synthesized in several parts of the body, including the pineal gland.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentBiopterins and derivatives
Alternative Parents
  • Biopterin
  • Aminopyrimidine
  • Pyrimidone
  • Secondary aliphatic/aromatic amine
  • Pyrimidine
  • 1,3-aminoalcohol
  • Vinylogous amide
  • Heteroaromatic compound
  • Secondary alcohol
  • 1,2-diol
  • 1,2-aminoalcohol
  • Secondary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physiological effect

Health effect:



Biological location:


Naturally occurring process:

Physical Properties
Experimental Properties
Melting Point250 - 255 °C (hydrochloride salt)Not Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility2.03 g/LALOGPS
pKa (Strongest Acidic)13.52ChemAxon
pKa (Strongest Basic)1.58ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area132 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity68.43 m³·mol⁻¹ChemAxon
Polarizability23.67 ųChemAxon
Number of Rings2ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon


Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (6 TMS)splash10-0zfr-2921300000-63bf6ee58b9df85919f62014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0zfr-2921300000-63bf6ee58b9df85919f62017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0005-9810000000-1bfd11724596b460cae92017-09-20View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-014i-6945000000-07faa91218e86d3bfe0d2017-10-06View Spectrum
MSMass Spectrum (Electron Ionization)splash10-00kb-9710000000-2a0077065c7181bedd5b2021-09-05View Spectrum


Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrum - QTOF 4V, positivesplash10-0006-0290000000-cd4c8c11b8279075b00a2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 5V, positivesplash10-0006-0390000000-35dddce9e2df2a9ac1982020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 7V, positivesplash10-0006-0590000000-cda875209a034e44cbe12020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 10V, positivesplash10-00kf-0980000000-53721c484501c528e7a82020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 15V, positivesplash10-014l-0930000000-533fabd35a8c5ca7830e2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 17V, positivesplash10-014i-0910000000-580c038db540047891c82020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 20V, positivesplash10-014i-0910000000-8d6b754dadadb63309062020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 3V, positivesplash10-0006-0090000000-f21b677255493f1f2d1f2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 23V, positivesplash10-014i-0900000000-5c1b60d0d7ea4dd4dbff2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 25V, positivesplash10-014i-1900000000-6f22457ab99b14bb653e2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 27V, positivesplash10-014i-1900000000-cd0410f4da61716c7f9e2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - QTOF 30V, positivesplash10-014i-2900000000-d4f18a979b6d07e83a632020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 16V, positivesplash10-0002-0900000000-87174b78444828c3b52d2020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 16V, positivesplash10-0a4i-0900000000-dc272a476d306f26c7222020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 16V, positivesplash10-014i-0900000000-ae19513d01a0046ed2e82020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 16V, positivesplash10-004i-0900000000-d4a52489d35bde573bd02020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 16V, positivesplash10-0f79-0900000000-af02b0d9eb8f6577afb82020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - n/a 16V, positivesplash10-014i-0900000000-c2259602e8f1fd522fd02020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 4V, positivesplash10-0006-0090000000-c88ed5ea9e11715bc2752020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 5V, positivesplash10-0006-0090000000-bcc7d633d824fb16f9142020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 6V, positivesplash10-0006-0290000000-840e21fdf6dd0f9fbe952020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 7V, positivesplash10-00kf-0590000000-6cffe3dadf67fa5bedb32020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 9V, positivesplash10-00kf-0970000000-617044dedfbb3eb488202020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 10V, positivesplash10-014l-0930000000-8368131601f86467c5552020-07-22View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Orbitrap 11V, positivesplash10-014i-0910000000-155462152d8128a097872020-07-22View Spectrum
Biological Properties
Cellular Locations
  • Nucleus
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
Tissue Locations
  • All Tissues
Normal Concentrations
BloodDetected and Quantified0.0110 +/- 0.0008 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.0093 +/- 0.0005 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.026 (0.014-0.038) uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BloodDetected and Quantified0.16 (0.0-5.8) uMAdult (>18 years old)Both
Septic shock
BloodDetected and Quantified1.2 (0.8-14.9) uMAdult (>18 years old)Both
Septic shock
BloodDetected and Quantified0.0099 +/- 0.0008 uMAdult (>18 years old)BothSmoking details
BloodDetected and Quantified0.0044 +/- 0.0007 uMAdult (>18 years old)Both
Myocardial infarction
Cerebrospinal Fluid (CSF)Detected and Quantified14400.0 uMNewborn (0-30 days old)BothGeneralized seizures details
FecesDetected but not QuantifiedNot QuantifiedChildren (1-13 years old)BothEnthesitis-related arthritis details
Associated Disorders and Diseases
Disease References
Septic shock
  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 ]
  1. Ueda S, Matsuoka H, Miyazaki H, Usui M, Okuda S, Imaizumi T: Tetrahydrobiopterin restores endothelial function in long-term smokers. J Am Coll Cardiol. 2000 Jan;35(1):71-5. [PubMed:10636262 ]
Myocardial infarction
  1. 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 ]
  1. 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 ]
Associated OMIM IDsNone
DrugBank IDDB00360
Phenol Explorer Compound IDNot Available
FooDB IDFDB021880
KNApSAcK IDC00018229
Chemspider ID40270
KEGG Compound IDC00272
BioCyc IDCPD-14053
BiGG IDNot Available
Wikipedia LinkTetrahydrobiopterin
METLIN IDNot Available
PubChem Compound44257
PDB IDNot Available
ChEBI ID59560
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000014
Synthesis ReferenceSteven S. Gross, "Blocking utilization of tetrahydrobiopterin to block induction of nitric oxide synthesis." U.S. Patent US5502050, issued October, 1984.
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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  17. Toda Y, Mori K, Hashimoto T, Miyazaki M, Nozaki S, Watanabe Y, Kuroda Y, Kagami S: Administration of secretin for autism alters dopamine metabolism in the central nervous system. Brain Dev. 2006 Mar;28(2):99-103. Epub 2005 Sep 15. [PubMed:16168596 ]
  18. Komori H, Matsuishi T, Yamada S, Yamashita Y, Ohtaki E, Kato H: Cerebrospinal fluid biopterin and biogenic amine metabolites during oral R-THBP therapy for infantile autism. J Autism Dev Disord. 1995 Apr;25(2):183-93. [PubMed:7559284 ]
  19. Kaufman S: Biopterin-responsive hyperphenylalaninemia. J Nutr Sci Vitaminol (Tokyo). 1992;Spec No:601-6. [PubMed:1297822 ]
  20. Sanford M, Keating GM: Spotlight on sapropterin in primary hyperphenylalaninemia. BioDrugs. 2009;23(3):201-2. doi: 10.2165/00063030-200923030-00007. [PubMed:19627172 ]
  21. MacDonald A, Ahring K, Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC, van Rijn M, Belanger-Quintana A: Adjusting diet with sapropterin in phenylketonuria: what factors should be considered? Br J Nutr. 2011 Jul;106(2):175-82. doi: 10.1017/S0007114511000298. [PubMed:21466737 ]
  22. Burton BK, Nowacka M, Hennermann JB, Lipson M, Grange DK, Chakrapani A, Trefz F, Dorenbaum A, Imperiale M, Kim SS, Fernhoff PM: Safety of extended treatment with sapropterin dihydrochloride in patients with phenylketonuria: results of a phase 3b study. Mol Genet Metab. 2011 Aug;103(4):315-22. doi: 10.1016/j.ymgme.2011.03.020. Epub 2011 Mar 31. [PubMed:21646032 ]
  23. Utz JR, Lorentz CP, Markowitz D, Rudser KD, Diethelm-Okita B, Erickson D, Whitley CB: START, a double blind, placebo-controlled pharmacogenetic test of responsiveness to sapropterin dihydrochloride in phenylketonuria patients. Mol Genet Metab. 2012 Feb;105(2):193-7. doi: 10.1016/j.ymgme.2011.10.014. Epub 2011 Oct 29. [PubMed:22112818 ]
  24. Gordon P, Thomas JA, Suter R, Jurecki E: Evolving patient selection and clinical benefit criteria for sapropterin dihydrochloride (Kuvan(R)) treatment of PKU patients. Mol Genet Metab. 2012 Apr;105(4):672-6. doi: 10.1016/j.ymgme.2011.12.023. Epub 2012 Jan 8. [PubMed:22310224 ]
  25. Leuret O, Barth M, Kuster A, Eyer D, de Parscau L, Odent S, Gilbert-Dussardier B, Feillet F, Labarthe F: Efficacy and safety of BH4 before the age of 4 years in patients with mild phenylketonuria. J Inherit Metab Dis. 2012 Nov;35(6):975-81. doi: 10.1007/s10545-012-9464-3. Epub 2012 Mar 3. [PubMed:22388642 ]
  26. Ziesch B, Weigel J, Thiele A, Mutze U, Rohde C, Ceglarek U, Thiery J, Kiess W, Beblo S: Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life. J Inherit Metab Dis. 2012 Nov;35(6):983-92. doi: 10.1007/s10545-012-9458-1. Epub 2012 Mar 6. [PubMed:22391997 ]
  27. Cunningham A, Bausell H, Brown M, Chapman M, DeFouw K, Ernst S, McClure J, McCune H, O'Steen D, Pender A, Skrabal J, Wessel A, Jurecki E, Shediac R, Prasad S, Gillis J, Cederbaum S: Recommendations for the use of sapropterin in phenylketonuria. Mol Genet Metab. 2012 Jul;106(3):269-76. doi: 10.1016/j.ymgme.2012.04.004. Epub 2012 Apr 13. [PubMed:22575621 ]
  28. Shintaku H, Ohwada M: Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan. Brain Dev. 2013 May;35(5):406-10. doi: 10.1016/j.braindev.2012.06.010. Epub 2012 Jul 24. [PubMed:22832064 ]
  29. Somaraju UR, Merrin M: Sapropterin dihydrochloride for phenylketonuria. Cochrane Database Syst Rev. 2012 Dec 12;12:CD008005. doi: 10.1002/14651858.CD008005.pub3. [PubMed:23235653 ]
  30. Gokmen Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC, van Rijn M, Ahring K, Belanger-Quintana A, MacDonald A, Dokoupil K: Use of sapropterin in the management of phenylketonuria: seven case reports. Mol Genet Metab. 2013 Feb;108(2):109-11. doi: 10.1016/j.ymgme.2012.11.012. Epub 2012 Nov 28. [PubMed:23266371 ]
  31. Thiele AG, Weigel JF, Ziesch B, Rohde C, Mutze U, Ceglarek U, Thiery J, Muller AS, Kiess W, Beblo S: Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH(4)). JIMD Rep. 2013;9:31-40. doi: 10.1007/8904_2012_176. Epub 2012 Oct 17. [PubMed:23430545 ]
  32. Cerone R, Andria G, Giovannini M, Leuzzi V, Riva E, Burlina A: Testing for tetrahydrobiopterin responsiveness in patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. Adv Ther. 2013 Mar;30(3):212-28. doi: 10.1007/s12325-013-0011-x. Epub 2013 Feb 20. [PubMed:23436109 ]
  33. Keil S, Anjema K, van Spronsen FJ, Lambruschini N, Burlina A, Belanger-Quintana A, Couce ML, Feillet F, Cerone R, Lotz-Havla AS, Muntau AC, Bosch AM, Meli CA, Billette de Villemeur T, Kern I, Riva E, Giovannini M, Damaj L, Leuzzi V, Blau N: Long-term follow-up and outcome of phenylketonuria patients on sapropterin: a retrospective study. Pediatrics. 2013 Jun;131(6):e1881-8. doi: 10.1542/peds.2012-3291. Epub 2013 May 20. [PubMed:23690520 ]
  34. Blau N: Sapropterin dihydrochloride for the treatment of hyperphenylalaninemias. Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1207-18. doi: 10.1517/17425255.2013.804064. Epub 2013 May 27. [PubMed:23705856 ]
  35. Douglas TD, Jinnah HA, Bernhard D, Singh RH: The effects of sapropterin on urinary monoamine metabolites in phenylketonuria. Mol Genet Metab. 2013 Jul;109(3):243-50. doi: 10.1016/j.ymgme.2013.04.017. Epub 2013 May 1. [PubMed:23712020 ]
  36. Stanhewicz AE, Alexander LM, Kenney WL: Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms. J Appl Physiol (1985). 2013 Oct 1;115(7):972-8. doi: 10.1152/japplphysiol.00481.2013. Epub 2013 Jun 6. [PubMed:23743404 ]
  37. Moens AL, Kass DA: Tetrahydrobiopterin and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2439-44. Epub 2006 Aug 31. [PubMed:16946131 ]

Only showing the first 10 proteins. There are 15 proteins in total.


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:
Uniprot ID:
Molecular weight:
  1. Wood JM, Schallreuter-Wood KU, Lindsey NJ, Callaghan S, Gardner ML: A specific tetrahydrobiopterin binding domain on tyrosinase controls melanogenesis. Biochem Biophys Res Commun. 1995 Jan 17;206(2):480-5. [PubMed:7826365 ]
General function:
Involved in monooxygenase activity
Specific function:
Plays an important role in the physiology of adrenergic neurons.
Gene Name:
Uniprot ID:
Molecular weight:
L-Tyrosine + Tetrahydrobiopterin + Oxygen → L-Dopa + 4a-Hydroxytetrahydrobiopterindetails
Tetrahydrobiopterin + L-Tyrosine + Oxygen → L-Dopa + 4a-Carbinolamine tetrahydrobiopterin + Waterdetails
  1. Madsen JT, Jansen P, Hesslinger C, Meyer M, Zimmer J, Gramsbergen JB: Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures. J Neurochem. 2003 Apr;85(1):214-23. [PubMed:12641743 ]
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
Uniprot ID:
Molecular weight:
L-Phenylalanine + Tetrahydrobiopterin + Oxygen → L-Tyrosine + 4a-Hydroxytetrahydrobiopterindetails
Tetrahydrobiopterin + L-Phenylalanine + Oxygen → 4a-Carbinolamine tetrahydrobiopterin + L-Tyrosine + Waterdetails
  1. Andersen OA, Flatmark T, Hough E: High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J Mol Biol. 2001 Nov 23;314(2):279-91. [PubMed:11718561 ]
General function:
Involved in 6-pyruvoyltetrahydropterin synthase activity
Specific function:
Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
Gene Name:
Uniprot ID:
Molecular weight:
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:
Uniprot ID:
Molecular weight:
Tetrahydrobiopterin + NADP → Dyspropterin + NADPHdetails
Tetrahydrobiopterin + NADP → 6-Lactoyltetrahydropterin + NADPH + Hydrogen Iondetails
  1. Auerbach G, Nar H: The pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase. Biol Chem. 1997 Mar-Apr;378(3-4):185-92. [PubMed:9165069 ]
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
Uniprot ID:
Molecular weight:
L-Tryptophan + Tetrahydrobiopterin + Oxygen → 5-Hydroxy-L-tryptophan + 4a-Hydroxytetrahydrobiopterindetails
Tetrahydrobiopterin + L-Tryptophan + Oxygen → 5-Hydroxy-L-tryptophan + 4a-Carbinolamine tetrahydrobiopterin + Waterdetails
  1. Sumi-Ichinose C, Urano F, Kuroda R, Ohye T, Kojima M, Tazawa M, Shiraishi H, Hagino Y, Nagatsu T, Nomura T, Ichinose H: Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A study from 6-pyruvoyltetrahydropterin synthase knockout mice. J Biol Chem. 2001 Nov 2;276(44):41150-60. Epub 2001 Aug 21. [PubMed:11517215 ]
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
Uniprot ID:
Molecular weight:
L-Tryptophan + Tetrahydrobiopterin + Oxygen → 5-Hydroxy-L-tryptophan + 4a-Hydroxytetrahydrobiopterindetails
Tetrahydrobiopterin + L-Tryptophan + Oxygen → 5-Hydroxy-L-tryptophan + 4a-Carbinolamine tetrahydrobiopterin + Waterdetails
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:
Uniprot ID:
Molecular weight:
4a-Carbinolamine tetrahydrobiopterin + NADH + Hydrogen Ion → Tetrahydrobiopterin + NADdetails
4a-Carbinolamine tetrahydrobiopterin + NADPH + Hydrogen Ion → Tetrahydrobiopterin + NADPdetails
  1. Shen RS: Inhibition of dopamine autoxidation by tetrahydrobiopterin and NADH in the presence of dihydropteridine reductase. Neurotoxicology. 1991 Summer;12(2):201-8. [PubMed:1956581 ]
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.
Gene Name:
Uniprot ID:
Molecular weight:
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:
Uniprot ID:
Molecular weight:
  1. Kamada Y, Jenkins GJ, Lau M, Dunbar AY, Lowe ER, Osawa Y: Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res Mol Brain Res. 2005 Dec 7;142(1):19-27. Epub 2005 Oct 10. [PubMed:16216381 ]

Only showing the first 10 proteins. There are 15 proteins in total.