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Record Information
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:02:43 UTC
Secondary Accession NumbersNone
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]-1,4-dihydropteridin-4-one
Traditional Name2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-1H-pteridin-4-one
CAS Registry Number22150-76-1
InChI Identifier
Chemical Taxonomy
DescriptionThis compound 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
  • Pyrimidone
  • Pyrimidine
  • Pyrazine
  • Primary aromatic amine
  • Heteroaromatic compound
  • Vinylogous amide
  • Secondary alcohol
  • 1,2-diol
  • Azacycle
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
StatusDetected and Quantified
  • Endogenous
  • Component of Phenylalanine, tyrosine and tryptophan biosynthesis
  • Component of Tyrosine metabolism
  • Enzyme co-factor
ApplicationNot Available
Cellular locations
  • Cytoplasm
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 mg/mLALOGPS
pKa (Strongest Acidic)7.6ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area133.72 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity58.13 m3·mol-1ChemAxon
Polarizability22.41 Å3ChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0aos-1922500000-07177d5a450dbf7c637aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-0190000000-cea25aa8258af5c9e837View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-004i-0900000000-32102578ef16c3df8f17View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a5c-5900000000-441b149b7ee5432cdac3View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cellular Cytoplasm
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Brain
  • Epidermis
  • Fibroblasts
  • Liver
  • Prostate
PathwaysNot Available
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 Quantified0.01-0.042 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
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 Quantified0.0085 +/- 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
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. [16289769 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022060
KNApSAcK IDNot Available
Chemspider ID392795
KEGG Compound IDC06313
BiGG IDNot Available
Wikipedia LinkBiopterin
NuGOwiki LinkHMDB00468
Metagene LinkHMDB00468
PubChem Compound445040
ChEBI ID63931
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. 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. [8178819 ]
  2. 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. [11443547 ]
  3. 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. [19212411 ]
  4. 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. [14728990 ]
  5. 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. [2969203 ]
  6. Snyderman SE, Sansaricq C, Pulmones MT: Successful long term therapy of biopterin deficiency. J Inherit Metab Dis. 1987;10(3):260-6. [3123784 ]
  7. 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. [6112078 ]
  8. Katoh S, Sueoka T, Matsuura S, Sugimoto T: Biopterin and neopterin in human saliva. Life Sci. 1989;45(26):2561-8. [2615555 ]
  9. 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. [12735910 ]
  10. 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. [16275037 ]
  11. 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. [1394977 ]
  12. 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. [1969283 ]
  13. 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. [2079836 ]
  14. 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. [12112113 ]
  15. 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. [11238300 ]
  16. Slazyk WE, Spierto FW: Liquid-chromatographic measurement of biopterin and neopterin in serum and urine. Clin Chem. 1990 Jul;36(7):1364-8. [2372953 ]
  17. 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. [3802534 ]
  18. 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. [9427887 ]
  19. 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. [2913929 ]
  20. Kaufman S: Hyperphenylalaninaemia caused by defects in biopterin metabolism. J Inherit Metab Dis. 1985;8 Suppl 1:20-7. [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.