Identification

Name
Sapropterin
Accession Number
DB00360  (APRD01297, EXPT00691, DB02692)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sapropterin (tetrahydrobiopterin or BH4) is a cofactor in the synthesis of nitric oxide. 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.

Structure
Thumb
Synonyms
  • (−)-(6R)-2-amino-6-((1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinone
  • (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
  • (6R)-L-erythro-tetrahydrobiopterin
  • 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1H)-pteridinone
  • 5,6,7,8-Tetrahydrobiopterin
  • 6R-5,6,7,8-tetrahydrobiopterin
  • 6R-BH4
  • 6R-L-5,6,7,8-tetrahydrobiopterin
  • R-THBP
  • Sapropterina
  • sapropterinum
  • Tetrahydrobiopterin
External IDs
17528-72-2 / 27070-47-9 / Sun 0588
Product Ingredients
IngredientUNIICASInChI Key
Sapropterin dihydrochlorideRG277LF5B369056-38-8RKSUYBCOVNCALL-NTVURLEBSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KuvanTablet100 mgOralBiomarin International Limited2010-07-05Not applicableCanada
KuvanPowder, for solution100 mg/1OralBiomarin International Limited2014-02-21Not applicableUs
KuvanTablet100 mg/1OralBiomarin International Limited2007-12-14Not applicableUs
KuvanPowder, for solution500 mg/1OralBiomarin International Limited2015-05-27Not applicableUs
International/Other Brands
BH4 (Excelsior) / Biopten (Daiichi Sankyo)
Categories
UNII
EGX657432I
CAS number
62989-33-7
Weight
Average: 241.2471
Monoisotopic: 241.117489371
Chemical Formula
C9H15N5O3
InChI Key
FNKQXYHWGSIFBK-RPDRRWSUSA-N
InChI
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)/t3-,4+,6-/m0/s1
IUPAC Name
(6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-3,4,5,6,7,8-hexahydropteridin-4-one
SMILES
[H][[email protected]@]1(CNC2=C(N1)C(=O)NC(N)=N2)[[email protected]@H](O)[[email protected]](C)O

Pharmacology

Indication

For the treatment of tetrahydrobiopterin (BH4) deficiency.

Structured Indications
Pharmacodynamics

Tetrahydrobiopterin (BH4) is used to convert several amino acids, including phenylalanine, to other essential molecules in the body including neurotransmitters. Tetrahydrobiopterin deficiency can be caused by mutations in GTP cyclohydrolase 1 (GCH1), 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (PCBD1), 6-pyruvoyltetrahydropterin synthase (PTS), and quinoid dihydropteridine reductase (QDPR) genes. These genes make the enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. High levels of phenylalanine can result in signs and symptoms ranging from temporary low muscle tone to mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.

Mechanism of action

Tetrahydrobiopterin (BH4) is a natural co-factor or co-enzyme for phenylalanine-4-hydroxylase (PAH),Tetrahydrobiopterine, and tryptophan-5-hydroxylase. Tetrahydrobiopterin is also a natural co-factor for nitrate oxide synthase. Therefore BH4 is required for the conversion of phenylalanine to tyrosine, for the production of epinephrine (adrenaline) and the synthesis of the monoamine neuro-transmitters, serotonin, dopamine, and norepinephrine (noradrenaline). It is also involved in apoptosis and other cellular events mediated by nitric oxide production. As a coenzyme, BH4 reacts with molecular oxygen to form an active oxygen intermediate that can hydroxylate substrates. In the hydroxylation process, the co-enzyme loses two electrons and is regenerated in vivo in an NADH-dependent reaction. As a co-factor for PAH, tetrahydrobiopterin allows the conversion of phenylalanine to tyrosine and reduces the level of phenylalanine in the bloodstream, thereby reducing the toxic effects of of this amino acid. Normal serum concentrations of phenylalanine are 100 micomolar, while elevated (toxic) levels are typically >1200 micromolar. Individuals with a deficiency in tetrahydrobiopterin are not able to efficiently convert phenylalanine to tyrosine. The excess levels provided by tetrahydrobiopterin supplementation help improve enzyme efficiency. As a co-factor for tyrosine hydroxylase, BH4 facilitates the conversion of tyrosine to L-dopa while as a co-factor for tryptophan hydroxylase, BH4 allows the conversion of tryptophan to 5-hydroxytryptophan, which is then converted to serotonin.

TargetActionsOrganism
APhenylalanine-4-hydroxylase
cofactor
Human
ANitric oxide synthase, endothelial
cofactor
Human
ATyrosine 3-monooxygenase
cofactor
Human
ATryptophan 5-hydroxylase 1
cofactor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Tryptophan MetabolismMetabolic
Tyrosinemia Type IDisease
Disulfiram Action PathwayDrug action
Pterine BiosynthesisMetabolic
Tyrosine MetabolismMetabolic
Prolidase Deficiency (PD)Disease
Segawa syndromeDisease
Tyrosinemia, transient, of the newbornDisease
Arginine and Proline MetabolismMetabolic
Prolinemia Type IIDisease
Hyperprolinemia Type IDisease
Dopa-responsive dystoniaDisease
Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiencyDisease
Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)Disease
AlkaptonuriaDisease
HawkinsinuriaDisease
Ornithine Aminotransferase Deficiency (OAT Deficiency)Disease
Hyperphenylalaninemia due to dhpr-deficiencyDisease
Dopamine beta-hydroxylase deficiencyDisease
Monoamine oxidase-a deficiency (MAO-A)Disease
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)Disease
Hyperprolinemia Type IIDisease
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)Disease
Sepiapterin reductase deficiencyDisease
Creatine deficiency, guanidinoacetate methyltransferase deficiencyDisease
Hyperornithinemia with gyrate atrophy (HOGA)Disease
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]Disease
L-arginine:glycine amidinotransferase deficiencyDisease
Doxorubicin Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AvanafilSapropterin may increase the hypotensive activities of Avanafil.Approved
LevodopaThe risk or severity of adverse effects can be increased when Sapropterin is combined with Levodopa.Approved
MethotrexateThe serum concentration of Sapropterin can be decreased when it is combined with Methotrexate.Approved
MirodenafilSapropterin may increase the hypotensive activities of Mirodenafil.Investigational
PralatrexateThe serum concentration of Sapropterin can be decreased when it is combined with Pralatrexate.Approved
SildenafilSapropterin may increase the hypotensive activities of Sildenafil.Approved, Investigational
TadalafilSapropterin may increase the hypotensive activities of Tadalafil.Approved, Investigational
UdenafilSapropterin may increase the hypotensive activities of Udenafil.Approved, Investigational
VardenafilSapropterin may increase the hypotensive activities of Vardenafil.Approved
Food Interactions
Not Available

References

Synthesis Reference

Steven S. Gross, "Blocking utilization of tetrahydrobiopterin to block induction of nitric oxide synthesis." U.S. Patent US5502050, issued October, 1984.

US5502050
General References
  1. Thony B, Auerbach G, Blau N: Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J. 2000 Apr 1;347 Pt 1:1-16. [PubMed:10727395]
External Links
Human Metabolome Database
HMDB59658
KEGG Drug
D08505
KEGG Compound
C00272
PubChem Compound
44257
PubChem Substance
46508597
ChemSpider
40270
BindingDB
50373697
ChEBI
59560
ChEMBL
CHEMBL1201774
Therapeutic Targets Database
DNC000425
PharmGKB
PA161990676
HET
H4B
Wikipedia
Tetrahydrobiopterin
ATC Codes
A16AX07 — Sapropterin
AHFS Codes
  • 92:92.00 — Other Miscellaneous Therapeutic Agents
PDB Entries
1d1v / 1d1w / 1d1x / 1df1 / 1dm8 / 1dwx / 1fop / 1j8u / 1jwj / 1k2r
show 462 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingBasic ScienceAging / Menopause1
0CompletedTreatmentHigh Blood Pressure (Hypertension)1
1CompletedTreatmentPhenylketonuria (PKU)1
1CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
1RecruitingBasic ScienceChronic Obstructive Pulmonary Disease (COPD) / Heart Failure, Unspecified / High Blood Pressure (Hypertension) / Pulmonary Arterial Hypertension (PAH)1
1Unknown StatusTreatmentPhenylketonuria (PKU)1
1, 2CompletedTreatmentGTP Cyclohydrolase Deficiency1
1, 2SuspendedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
2Active Not RecruitingTreatmentAlzheimer's Disease (AD)1
2CompletedNot AvailableCystic Fibrosis (CF)1
2CompletedTreatmentAlbuminuria / Kidney Diseases1
2CompletedTreatmentAutistic Disorder1
2CompletedTreatmentEndothelial Dysfunction1
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentHyperphenylalaninemia, Non-Phenylketonuric / Tetrahydrobiopterin Deficiencies1
2CompletedTreatmentIntermittent Claudication1
2CompletedTreatmentKidney Failure,Chronic1
2CompletedTreatmentPhenylketonuria (PKU)1
2CompletedTreatmentPhenylketonurias1
2CompletedTreatmentSickle Cell Disorders1
2RecruitingSupportive CareRenal Insufficiency,Chronic1
2RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2TerminatedNot AvailablePhenylketonuria (PKU)1
2TerminatedTreatmentPhenylketonuria (PKU)1
2Unknown StatusTreatmentCoronary Artery Disease1
2Unknown StatusTreatmentEndothelial Dysfunction / Isolated Systolic Hypertension (ISH)1
2, 3CompletedTreatmentAutistic Disorder1
2, 3CompletedTreatmentLiver Cirrhosis / Portal Hypertension1
2, 3TerminatedTreatmentPhenylalanine Hydroxylase Deficiencies1
2, 3WithdrawnTreatmentBehavioral Manifestations of Lesch-Nyhan Disease1
3Active Not RecruitingTreatmentPhenylketonuria (PKU)2
3CompletedTreatmentPhenylketonuria (PKU)3
3CompletedTreatmentPhenylketonurias2
4Active Not RecruitingTreatmentPhenylketonuria (PKU)1
4CompletedTreatmentPhenylketonuria (PKU)2
4RecruitingTreatmentPhenylketonuria (PKU)1
Not AvailableApproved for MarketingNot AvailablePhenylketonuria (PKU)1
Not AvailableCompletedNot AvailablePhenylketonuria (PKU)2
Not AvailableCompletedPreventionPulmonary Disease, Chronic Obstructive1
Not AvailableCompletedTreatmentAutism Spectrum Conditions/Disorders1
Not AvailableCompletedTreatmentPhenylketonuria (PKU)1
Not AvailableRecruitingNot AvailableHyperphenylalaninemia / Phenylketonuria (PKU)1
Not AvailableRecruitingNot AvailableRheumatologic Diseases1
Not AvailableRecruitingTreatmentCardiovascular Disease (CVD) / Heart Failure, Unspecified1
Not AvailableTerminatedNot AvailablePhenylketonuria (PKU)2
Not AvailableTerminatedTreatmentHyperphenylalaninemia / Phenylketonuria (PKU)1
Not AvailableUnknown StatusNot AvailablePhenylketonuria (PKU)1
Not AvailableUnknown StatusTreatmentBehavior and Behavior Mechanisms / PAH Gene Expression / Phenylketonuria (PKU)1
Not AvailableUnknown StatusTreatmentGastroparesis1
Not AvailableUnknown StatusTreatmentPhenylketonuria (PKU)1
Not AvailableWithdrawnDiagnosticPhenylketonuria (PKU)1

Pharmacoeconomics

Manufacturers
  • Biomarin pharmaceutical inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionOral100 mg/1
Powder, for solutionOral500 mg/1
TabletOral100 mg
TabletOral100 mg/1
Prices
Unit descriptionCostUnit
Kuvan 100 mg tablet36.5USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2545968No2010-03-092024-11-17Canada
US7566714Yes2005-05-172025-05-17Us
US7612073Yes2005-05-172025-05-17Us
US8067416Yes2005-05-172025-05-17Us
USRE43797Yes2005-05-172025-05-17Us
US7947681Yes2005-05-172025-05-17Us
US7566462Yes2006-05-162026-05-16Us
US8318745Yes2005-05-172025-05-17Us
US8003126Yes2006-05-162026-05-16Us
US7727987Yes2005-05-172025-05-17Us
US9216178No2012-11-012032-11-01Us
US9433624No2004-11-172024-11-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)250-255 °C (hydrochloride salt)Not Available
water solubility>20 mg/mL (dichloride salt)Not Available
logP-1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.03 mg/mLALOGPS
logP-1.8ALOGPS
logP-2.3ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)11.12ChemAxon
pKa (Strongest Basic)4.61ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area132 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity68.63 m3·mol-1ChemAxon
Polarizability23.61 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9938
Blood Brain Barrier+0.5558
Caco-2 permeable-0.6674
P-glycoprotein substrateSubstrate0.785
P-glycoprotein inhibitor INon-inhibitor0.9599
P-glycoprotein inhibitor IINon-inhibitor0.9881
Renal organic cation transporterNon-inhibitor0.8946
CYP450 2C9 substrateNon-substrate0.768
CYP450 2D6 substrateNon-substrate0.78
CYP450 3A4 substrateNon-substrate0.5278
CYP450 1A2 substrateNon-inhibitor0.91
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9227
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9348
Ames testNon AMES toxic0.6328
CarcinogenicityNon-carcinogens0.9271
BiodegradationNot ready biodegradable0.9607
Rat acute toxicity2.4428 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.993
hERG inhibition (predictor II)Non-inhibitor0.6937
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (6 TMS)GC-MSsplash10-0zfr-2921300000-63bf6ee58b9df85919f6
GC-MS Spectrum - GC-MSGC-MSsplash10-0zfr-2921300000-63bf6ee58b9df85919f6
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-006x-0090000000-e6b01d1139ccb3c6338d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0gi3-0980000000-8963ef41f1138b05a813
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00xr-1900000000-bcfa359703563c696c0f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0390000000-4810efa20f31adea3824
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-006y-1930000000-5b32feeb643e238bb159
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9400000000-a7dbebeb1df4ea110948

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pteridines and derivatives
Sub Class
Pterins and derivatives
Direct Parent
Biopterins and derivatives
Alternative Parents
Secondary alkylarylamines / Pyrimidones / Aminopyrimidines and derivatives / Vinylogous amides / Heteroaromatic compounds / 1,3-aminoalcohols / Secondary alcohols / 1,2-diols / 1,2-aminoalcohols / Azacyclic compounds
show 4 more
Substituents
Biopterin / Aminopyrimidine / Pyrimidone / Secondary aliphatic/aromatic amine / Pyrimidine / 1,3-aminoalcohol / Vinylogous amide / Heteroaromatic compound / Secondary alcohol / 1,2-diol
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
5,6,7,8-tetrahydrobiopterin (CHEBI:59560) / Coenzymes (C00272)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Phenylalanine 4-monooxygenase activity
Specific Function
Not Available
Gene Name
PAH
Uniprot ID
P00439
Uniprot Name
Phenylalanine-4-hydroxylase
Molecular Weight
51861.565 Da
References
  1. Zekanowski C, Nowacka M, Sendecka E, Sowik M, Cabalska B, Bal J: Identification of Mutations Causing 6-Pyruvoyl- Tetrahydrobiopterin Synthase Deficiency in Polish Patients With Variant Hyperphenylalaninemia. Mol Diagn. 1998 Dec;3(4):237-239. [PubMed:10089284]
  2. Werner ER, Habisch HJ, Gorren AC, Schmidt K, Canevari L, Werner-Felmayer G, Mayer B: Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase. Biochem J. 2000 Jun 15;348 Pt 3:579-83. [PubMed:10839989]
  3. Fitzpatrick PF: Tetrahydropterin-dependent amino acid hydroxylases. Annu Rev Biochem. 1999;68:355-81. [PubMed:10872454]
  4. Ayling JE, Bailey SW, Boerth SR, Giugliani R, Braegger CP, Thony B, Blau N: Hyperphenylalaninemia and 7-pterin excretion associated with mutations in 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH: analysis of enzyme activity in intestinal biopsies. Mol Genet Metab. 2000 Jul;70(3):179-88. [PubMed:10924272]
  5. Jennings IG, Teh T, Kobe B: Essential role of the N-terminal autoregulatory sequence in the regulation of phenylalanine hydroxylase. FEBS Lett. 2001 Jan 19;488(3):196-200. [PubMed:11163771]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induce...
Gene Name
NOS3
Uniprot ID
P29474
Uniprot Name
Nitric oxide synthase, endothelial
Molecular Weight
133287.62 Da
References
  1. Heller R, Munscher-Paulig F, Grabner R, Till U: L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells. J Biol Chem. 1999 Mar 19;274(12):8254-60. [PubMed:10075731]
  2. Huang A, Vita JA, Venema RC, Keaney JF Jr: Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem. 2000 Jun 9;275(23):17399-406. [PubMed:10749876]
  3. Berka V, Tsai AL: Characterization of interactions among the heme center, tetrahydrobiopterin, and L-arginine binding sites of ferric eNOS using imidazole, cyanide, and nitric oxide as probes. Biochemistry. 2000 Aug 8;39(31):9373-83. [PubMed:10924132]
  4. Gorren AC, Bec N, Schrammel A, Werner ER, Lange R, Mayer B: Low-temperature optical absorption spectra suggest a redox role for tetrahydrobiopterin in both steps of nitric oxide synthase catalysis. Biochemistry. 2000 Sep 26;39(38):11763-70. [PubMed:10995244]
  5. Shinozaki K, Nishio Y, Okamura T, Yoshida Y, Maegawa H, Kojima H, Masada M, Toda N, Kikkawa R, Kashiwagi A: Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats. Circ Res. 2000 Sep 29;87(7):566-73. [PubMed:11009561]
  6. Gorren AC, Mayer B: Tetrahydrobiopterin in nitric oxide synthesis: a novel biological role for pteridines. Curr Drug Metab. 2002 Apr;3(2):133-57. [PubMed:12003347]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Tyrosine 3-monooxygenase activity
Specific Function
Plays an important role in the physiology of adrenergic neurons.
Gene Name
TH
Uniprot ID
P07101
Uniprot Name
Tyrosine 3-monooxygenase
Molecular Weight
58599.545 Da
References
  1. Koshimura K, Tanaka J, Murakami Y, Kato Y: Enhancement of neuronal survival by 6R-tetrahydrobiopterin. Neuroscience. 1999 Jan;88(2):561-9. [PubMed:10197775]
  2. Flatmark T, Almas B, Knappskog PM, Berge SV, Svebak RM, Chehin R, Muga A, Martinez A: Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. Eur J Biochem. 1999 Jun;262(3):840-9. [PubMed:10411647]
  3. Ichinose H, Ohye T, Suzuki T, Inagaki H, Nagatsu T: [The relation between metabolism of biopterin and dystonia-parkinsonism]. Nihon Shinkei Seishin Yakurigaku Zasshi. 1999 Apr;19(2):85-9. [PubMed:10464780]
  4. Schwarz EJ, Alexander GM, Prockop DJ, Azizi SA: Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease. Hum Gene Ther. 1999 Oct 10;10(15):2539-49. [PubMed:10543618]
  5. Schallreuter KU: A review of recent advances on the regulation of pigmentation in the human epidermis. Cell Mol Biol (Noisy-le-grand). 1999 Nov;45(7):943-9. [PubMed:10643998]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Tryptophan 5-monooxygenase activity
Specific Function
Not Available
Gene Name
TPH1
Uniprot ID
P17752
Uniprot Name
Tryptophan 5-hydroxylase 1
Molecular Weight
50984.725 Da
References
  1. Chamas F, Serova L, Sabban EL: Tryptophan hydroxylase mRNA levels are elevated by repeated immobilization stress in rat raphe nuclei but not in pineal gland. Neurosci Lett. 1999 Jun 4;267(3):157-60. [PubMed:10381000]
  2. Martinez A, Knappskog PM, Haavik J: A structural approach into human tryptophan hydroxylase and its implications for the regulation of serotonin biosynthesis. Curr Med Chem. 2001 Jul;8(9):1077-91. [PubMed:11472242]
  3. Ikemoto K, Suzuki T, Ichinose H, Ohye T, Nishimura A, Nishi K, Nagatsu I, Nagatsu T: Localization of sepiapterin reductase in the human brain. Brain Res. 2002 Nov 8;954(2):237-46. [PubMed:12414107]
  4. Serova LI, Maharjan S, Huang A, Sun D, Kaley G, Sabban EL: Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration. Brain Res. 2004 Jul 23;1015(1-2):1-8. [PubMed:15223360]
  5. Haavik J: [From butterflies to neurobiology and the diagnosis of AIDS. The 100th anniversary of the discovery of pteridines]. Tidsskr Nor Laegeforen. 1989 Jun 30;109(19-21):1986-9. [PubMed:2665179]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Chae SW, Bang YJ, Kim KM, Lee KY, Kang BY, Kim EM, Inoue H, Hwang O, Choi HJ: Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation. Biochem Biophys Res Commun. 2007 Aug 3;359(3):735-41. Epub 2007 Jun 4. [PubMed:17560944]

Drug created on June 13, 2005 07:24 / Updated on December 10, 2017 17:18