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Record Information
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-10-09 20:59:24 UTC
Secondary Accession Numbers
  • HMDB00468
Metabolite Identification
Common NameBiopterin
DescriptionBiopterin concentrations in cerebrospinal fluid from patients with Parkinson's disease, in which the nigrostriatal dopamine neurons degenerate, are lower than those from age-matched older controls. In hereditary progressive dystonia/DOPA-responsive dystonia, which is a dopamine deficiency caused by mutations in GTP cyclohydrolase I without neuronal cell death (Segawa's disease), neopterin and biopterin in cerebrospinal fluid decrease in parallel owing to the decreased activity in GTP cyclohydrolase I. GTP cyclohydrolase I (EC is an enzyme that is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin 3'-triphosphate. (Pteridines (1999), 10(1), 5-13.) Lowered levels of urinary biopterin concomitant with elevated serum phenylalanine concentration occur in a variant type of hyperphenylalaninemia caused by a deficiency of tetrahydrobiopterin (BH4), the obligatory cofactor for phenylalanine hydroxylase. The most frequent form of this cofactor deficiency is due to lack of 6-pyruvoyl-tetrahydropterin synthase (PTPS) activity, the second enzyme in the biosynthetic pathway for BH4. (PMID 8178819 ) The hepatic phenylalanine hydroxylating system consists of 3 essential components, phenylalanine hydroxylase, dihydropteridine reductase, and the nonprotein coenzyme, tetrahydrobiopterin. The reductase and the pterin coenzyme are also essential components of the tyrosine and tryptophan hydroxylating systems. There are 3 distinct forms of phenylketonuria or hyperphenylalaninemia, each caused by lack of 1 of these essential components. The variant forms of the disease that are caused by the lack of dihydropteridine reductase or tetrahydrobiopterin are characterized by severe neurol. deterioration, impaired functioning of tyrosine and tryptophan hydroxylases, and the resultant deficiency of tyrosine- and tryptophan-derived monoamine neurotransmitters in brain. (PMID 3930837 ).
(1'r,1's) BiopterinHMDB
Pterin H b2HMDB
Chemical FormulaC9H11N5O3
Average Molecular Weight237.2153
Monoisotopic Molecular Weight237.086189243
IUPAC Name2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-4,8-dihydropteridin-4-one
Traditional Name2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-8H-pteridin-4-one
CAS Registry Number22150-76-1
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
  • Pyrazine
  • Pyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • 1,2-diol
  • Secondary alcohol
  • Azacycle
  • Organic oxygen compound
  • Alcohol
  • Aromatic alcohol
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organic oxide
  • Amine
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors


Biological location:

Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.7 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility4.06 g/LALOGPS
pKa (Strongest Acidic)8.18ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area132.66 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity57.81 m³·mol⁻¹ChemAxon
Polarizability22.47 ųChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0aos-1922500000-07177d5a450dbf7c637aSpectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0aos-1922500000-07177d5a450dbf7c637aSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-3910000000-90aa51259ebfb8feb1f5Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-044i-5094000000-cf05a1ca25a8f1348f75Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-0190000000-cea25aa8258af5c9e837Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-004i-0900000000-32102578ef16c3df8f17Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a5c-5900000000-441b149b7ee5432cdac3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0079-0090000000-8aa892a20d8030a22d50Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dr-0190000000-55344345937d9883d783Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0h91-1920000000-a6b8c5b9d802ce02b0c5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0290000000-f8e54aa1d030a0c8a29dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0940000000-c3bcfa7320d53b878000Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9800000000-3ab4f0aaf7f070e3ae28Spectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Cellular Cytoplasm
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Locations
  • Brain
  • Epidermis
  • Fibroblasts
  • Liver
  • Prostate
Normal Concentrations
BloodDetected and Quantified0.017 +/- 0.0025 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
Cellular CytoplasmDetected and Quantified0.033 +/- 0.0073 uMAdult (>18 years old)Not SpecifiedNormal
    • Geigy Scientific ...
Cerebrospinal Fluid (CSF)Detected and Quantified0.026 - 0.052 uMNewborn (0-30 days old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.021 - 0.038 uMInfant (0-1 year old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0132 +/- 0.0005 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0140-0.0360 uMAdolescent (13-18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.01-0.042 uMChildren (1-13 years old)MaleNormal details
UrineDetected and Quantified0.24 +/- 0.07 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
UrineDetected and Quantified0.32 +/- 0.13 umol/mmol creatinineAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
UrineDetected and Quantified0.48 +/- 0.17 umol/mmol creatinineChildren (1-13 years old)BothNormal
    • Geigy Scientific ...
UrineDetected and Quantified0.13 +/- 0.084 umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified0.3 +/- 0.14 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified0.82 +/- 0.34 umol/mmol creatinineNewborn (0-30 days old)FemaleNormal details
UrineDetected and Quantified0.5-3.0 umol/mmol creatinineNewborn (0-30 days old)Not SpecifiedNormal details
Abnormal Concentrations
Cerebrospinal Fluid (CSF)Detected and Quantified0.0376 (0.0281-0.0471) uMChildren (1-13 years old)Malesepiapterin reductase deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified0.01 uMAdolescent (13-18 years old)Not AvailableUrocanase deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0085 +/- 0.0003 uMNot SpecifiedNot Specifiedidiopathic parkinsonisam details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0142 +/- 0.0012 uMNot SpecifiedNot Specifieddopa-nonresponsive dystonia details
Cerebrospinal Fluid (CSF)Detected and Quantified20.6 (19.2 - 22.0) uMAdult (>18 years old)Not SpecifiedSegawa Syndrome details
UrineDetected and Quantified0.19-0.63 umol/mmol creatinineNewborn (0-30 days old)BothHyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (PTPS) details
UrineDetected and Quantified0.62 umol/mmol creatinineNewborn (0-30 days old)FemaleHyperphenylalaninemia due to pterin-4a-carbinolamine dehydratase details
Associated Disorders and Diseases
Disease References
Segawa Syndrome
  1. Furuya H, Murai H, Takasugi K, Ohyagi Y, Urano F, Kishi T, Ichinose H, Kira J: A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene. Clin Neurol Neurosurg. 2006 Dec;108(8):784-6. Epub 2005 Nov 14. [PubMed:16289769 ]
Sepiapterin reductase deficiency
  1. Verbeek MM, Willemsen MA, Wevers RA, Lagerwerf AJ, Abeling NG, Blau N, Thony B, Vargiami E, Zafeiriou DI: Two Greek siblings with sepiapterin reductase deficiency. Mol Genet Metab. 2008 Aug;94(4):403-9. doi: 10.1016/j.ymgme.2008.04.003. Epub 2008 May 27. [PubMed:18502672 ]
Parkinson's disease
  1. Furukawa Y, Nishi K, Mizuno Y, Narabayashi H: [Significance of CSF biopterin and neopterin in hereditary progressive dystonia with marked diurnal fluctuation (HPD)--a clue to pathogenesis]. No To Shinkei. 1995 Mar;47(3):261-8. [PubMed:7669428 ]
Urocanase deficiency
  1. Espinos C, Pineda M, Martinez-Rubio D, Lupo V, Ormazabal A, Vilaseca MA, Spaapen LJ, Palau F, Artuch R: Mutations in the urocanase gene UROC1 are associated with urocanic aciduria. J Med Genet. 2009 Jun;46(6):407-11. doi: 10.1136/jmg.2008.060632. Epub 2009 Mar 19. [PubMed:19304569 ]
6-Pyruvoyltetrahydropterin synthase deficiency
  1. Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW: Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase. Am J Hum Genet. 1994 May;54(5):782-92. [PubMed:8178819 ]
Pterin-4a carbinolamine dehydratase deficiency
  1. Blaskovics M, Giudici TA: A new variant of biopterin deficiency. N Engl J Med. 1988 Dec 15;319(24):1611-2. doi: 10.1056/NEJM198812153192420. [PubMed:3200274 ]
Associated OMIM IDs
  • 128230 (Segawa Syndrome)
  • 182125 (Sepiapterin reductase deficiency)
  • 168600 (Parkinson's disease)
  • 276880 (Urocanase deficiency)
  • 261640 (6-Pyruvoyltetrahydropterin synthase deficiency)
  • 264070 (Pterin-4a carbinolamine dehydratase deficiency)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022060
KNApSAcK IDNot Available
Chemspider ID392795
KEGG Compound IDC06313
BioCyc IDCPD-10819
BiGG IDNot Available
Wikipedia LinkBiopterin
PubChem Compound445040
PDB IDNot Available
ChEBI ID63931
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000167
Synthesis ReferenceMori, Kenji; Kikuchi, Haruhiko. Synthesis of (-)-biopterin. Liebigs Annalen der Chemie (1989), (10), 963-7.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Fiege B, Ballhausen D, Kierat L, Leimbacher W, Goriounov D, Schircks B, Thony B, Blau N: Plasma tetrahydrobiopterin and its pharmacokinetic following oral administration. Mol Genet Metab. 2004 Jan;81(1):45-51. [PubMed:14728990 ]
  2. Friedland RP, Koss E, Haxby JV, Grady CL, Luxenberg J, Schapiro MB, Kaye J: NIH conference. Alzheimer disease: clinical and biological heterogeneity. Ann Intern Med. 1988 Aug 15;109(4):298-311. [PubMed:2969203 ]
  3. Snyderman SE, Sansaricq C, Pulmones MT: Successful long term therapy of biopterin deficiency. J Inherit Metab Dis. 1987;10(3):260-6. [PubMed:3123784 ]
  4. Nagatsu T, Yamaguchi T, Kato T, Sugimoto T, Matsuura S, Akino M, Nagatsu I, Iizuka R, Narabayashi H: Biopterin in human brain and urine from controls and parkinsonian patients: application of a new radioimmunoassay. Clin Chim Acta. 1981 Feb 5;109(3):305-11. [PubMed:6112078 ]
  5. Katoh S, Sueoka T, Matsuura S, Sugimoto T: Biopterin and neopterin in human saliva. Life Sci. 1989;45(26):2561-8. [PubMed:2615555 ]
  6. Ichinose H, Ohye T, Shinotoh H, Arai K, Yamazaki S, Mizuta E, Kuno S, Nagatsu T: Biopterin metabolism in patients with malignant syndrome. Parkinsonism Relat Disord. 2003 Apr;9 Suppl 1:S11-4. [PubMed:12735910 ]
  7. Zurfluh MR, Giovannini M, Fiori L, Fiege B, Gokdemir Y, Baykal T, Kierat L, Gartner KH, Thony B, Blau N: Screening for tetrahydrobiopterin deficiencies using dried blood spots on filter paper. Mol Genet Metab. 2005 Dec;86 Suppl 1:S96-103. Epub 2005 Nov 7. [PubMed:16275037 ]
  8. Ogiwara S, Kiuchi K, Nagatsu T, Teradaira R, Nagatsu I, Fujita K, Sugimoto T: Highly sensitive, specific enzyme-linked immunosorbent assay of neopterin and biopterin in biological samples. Clin Chem. 1992 Oct;38(10):1954-8. [PubMed:1394977 ]
  9. Hirata Y, Sawada M, Minami M, Arai H, Iizuka R, Nagatsu T: Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and neopterin in the brain of anorexia nervosa. J Neural Transm Gen Sect. 1990;80(2):145-50. [PubMed:1969283 ]
  10. Dhondt JL, Tilmont P, Ringel J, Farriaux JP: Pterins analysis in amniotic fluid for the prenatal diagnosis of GTP cyclohydrolase deficiency. J Inherit Metab Dis. 1990;13(6):879-82. [PubMed:2079836 ]
  11. Furukawa Y, Kapatos G, Haycock JW, Worsley J, Wong H, Kish SJ, Nygaard TG: Brain biopterin and tyrosine hydroxylase in asymptomatic dopa-responsive dystonia. Ann Neurol. 2002 May;51(5):637-41. [PubMed:12112113 ]
  12. 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 ]
  13. Bonafe L, Thony B, Leimbacher W, Kierat L, Blau N: Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts. Clin Chem. 2001 Mar;47(3):477-85. [PubMed:11238300 ]
  14. Slazyk WE, Spierto FW: Liquid-chromatographic measurement of biopterin and neopterin in serum and urine. Clin Chem. 1990 Jul;36(7):1364-8. [PubMed:2372953 ]
  15. Dhondt JL, Hayte JM, Forzy G, Delcroix M, Farriaux JP: Unconjugated pteridines in amniotic fluid during gestation. Clin Chim Acta. 1986 Dec 30;161(3):269-73. [PubMed:3802534 ]
  16. Iizuka T, Sasaki M, Oishi K, Uemura S, Koike M, Minatogawa Y: Nitric oxide may trigger lactation in humans. J Pediatr. 1997 Dec;131(6):839-43. [PubMed:9427887 ]
  17. Zoghbi HY, Milstien S, Butler IJ, Smith EO, Kaufman S, Glaze DG, Percy AK: Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome. Ann Neurol. 1989 Jan;25(1):56-60. [PubMed:2913929 ]
  18. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
  19. Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW: Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase. Am J Hum Genet. 1994 May;54(5):782-92. [PubMed:8178819 ]
  20. Kaufman S: Hyperphenylalaninaemia caused by defects in biopterin metabolism. J Inherit Metab Dis. 1985;8 Suppl 1:20-7. [PubMed:3930837 ]
  21. (). Nagatsu T, Ichinose H, Mogi M, Togari A (1999) Neopterin and cytokines in hereditary dystonia and Parkinson’s disease. Pteridines 10: 5–13.. .