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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:29:57 UTC
HMDB IDHMDB00980
Secondary Accession Numbers
  • HMDB01144
  • HMDB12181
Metabolite Identification
Common NameDihydroneopterin triphosphate
DescriptionThe biosynthesis of tetrahydrobiopterin (BH4) from dihydroneopterin triphosphate (NH2P3) was studied in human liver extract. The phosphate-eliminating enzyme (PEE) was purified approximately 750-fold. The conversion of NH2P3 to BH4 was catalyzed by this enzyme in the presence of partially purified sepiapterin reductase, Mg2+ and NADPH. The PEE is heat stable when heated at 80 degrees C for 5 min. It has a molecular weight of 63 000 daltons. One possible intermediate 6-(1'-hydroxy-2'-oxopropyl)5,6,7,8-tetrahydropterin(2'-oxo-tetrahydropte rin) was formed upon incubation of BH4 in the presence of sepiapterin reductase and NADP+ at pH 9.0. Reduction of this compound with NaBD4 yielded monodeutero threo and erythro-BH4, the deuterium was incorporated at the 2' position. This and the UV spectra were consistent with a 2'-oxo-tetrahydropterin structure. Dihydrofolate reductase (DHFR) catalyzed the reduction of BH2 to BH4 and was found to be specific for the pro-R-NADPH side. The sepiapterin reductase catalyzed the transfer of the pro-S hydrogen of NADPH during the reduction of sepiapterin to BH2. In the presence of crude liver extracts the conversion of NH2P3 to BH4 requires NADPH. Two deuterium atoms were incorporated from (4S-2H)NADHP in the 1' and 2' position of the BH4 side chain. Incorporation of one hydrogen from the solvent was found at position C(6). These results are consistent with the occurrence of an intramolecular redox exchange between the pteridine nucleus and the side chain and formation of 6-pyruvoyl-5,6,7,8-tetrahydropterin(tetrahydro-1'-2'-dioxopterin) as intermediate. PMID: 3930838 .
Structure
Thumb
Synonyms
  1. 2-Amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl) dihydropteridine triphosphate
  2. 6-(L-Erythro-1,2-Dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
  3. 6-[(1S,2R)-1,2-Dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin
  4. 7,8-Dihydroneopterin 3'-triphosphate
  5. 7,8-Dihydroneopterin triphosphate
Chemical FormulaC9H16N5O13P3
Average Molecular Weight495.1703
Monoisotopic Molecular Weight494.995745159
IUPAC Name{[({[(2R,3S)-3-(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)-2,3-dihydroxypropoxy](hydroxy)phosphoryl}oxy)(hydroxy)phosphoryl]oxy}phosphonic acid
Traditional Name{[(2R,3S)-3-(2-amino-4-oxo-7,8-dihydro-3H-pteridin-6-yl)-2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy(hydroxy)phosphoryl}oxyphosphonic acid
CAS Registry Number20574-65-6
SMILES
NC1=NC2=C(N=C(CN2)[C@H](O)[C@H](O)COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(=O)N1
InChI Identifier
InChI=1S/C9H16N5O13P3/c10-9-13-7-5(8(17)14-9)12-3(1-11-7)6(16)4(15)2-25-29(21,22)27-30(23,24)26-28(18,19)20/h4,6,15-16H,1-2H2,(H,21,22)(H,23,24)(H2,18,19,20)(H4,10,11,13,14,17)/t4-,6+/m1/s1
InChI KeyDGGUVLXVLHAAGT-XINAWCOVSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassPteridines and Derivatives
Sub ClassPterins and Derivatives
Other Descriptors
  • Pterins and Derivatives
  • dihydropterin(ChEBI)
  • neopterins(ChEBI)
  • pterin phosphate(ChEBI)
Substituents
  • 1,2 Diol
  • 1,3 Aminoalcohol
  • Aminopyrimidine
  • Imine
  • Monosaccharide Phosphate
  • Organic Hypophosphite
  • Organic Phosphite
  • Organic Pyrophosphate
  • Phosphoric Acid Ester
  • Pyrimidine
  • Pyrimidone
  • Saccharide
  • Secondary Alcohol
  • Triose Monosaccharide
Direct ParentBiopterins and Derivatives
Ontology
StatusExpected and Not Quantified
Origin
  • Endogenous
Biofunction
  • Component of Folate biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.62 g/LALOGPS
logP-0.77ALOGPS
logP-4.5ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)0.89ChemAxon
pKa (Strongest Basic)3.68ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area292.15ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity102.48ChemAxon
Polarizability36.75ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid LocationsNot Available
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Pterine BiosynthesisSMP00005map00790
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022349
KNApSAcK IDNot Available
Chemspider ID108735
KEGG Compound IDC04895
BioCyc ID6-1S2R-12-DIHYDROXY-3-TRIPHOSPHOOXY
BiGG ID44843
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00980
Metagene LinkHMDB00980
METLIN ID5917
PubChem Compound121885
PDB IDNot Available
ChEBI ID18372
References
Synthesis ReferenceFerre, Juan; Naylor, Edwin W.; Jacobson, K. Bruce. Repetitive recycling of guanosine triphosphate cyclohydrolase I for synthesis of dihydroneopterin triphosphate. Analytical Biochemistry (1989), 176(1), 15-18.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Curtius HC, Heintel D, Ghisla S, Kuster T, Leimbacher W, Niederwieser A: Biosynthesis of tetrahydrobiopterin in man. J Inherit Metab Dis. 1985;8 Suppl 1:28-33. Pubmed: 3930838

Enzymes

General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
ALPP
Uniprot ID:
P05187
Molecular weight:
57953.31
Reactions
Dihydroneopterin triphosphate + Water → 7,8-Dihydroneopterin + Phosphoric aciddetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
ALPI
Uniprot ID:
P09923
Molecular weight:
56811.695
Reactions
Dihydroneopterin triphosphate + Water → 7,8-Dihydroneopterin + Phosphoric aciddetails
General function:
Involved in catalytic activity
Specific function:
This isozyme may play a role in skeletal mineralization.
Gene Name:
ALPL
Uniprot ID:
P05186
Molecular weight:
57304.435
Reactions
Dihydroneopterin triphosphate + Water → 7,8-Dihydroneopterin + Phosphoric aciddetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
ALPPL2
Uniprot ID:
P10696
Molecular weight:
57376.515
Reactions
Dihydroneopterin triphosphate + Water → 7,8-Dihydroneopterin + Phosphoric aciddetails
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:
PTS
Uniprot ID:
Q03393
Molecular weight:
16385.63
Reactions
Dihydroneopterin triphosphate → Dyspropterin + Triphosphatedetails
Dihydroneopterin triphosphate → Dyspropterin + PPPidetails
Dihydroneopterin triphosphate + Water → 6-Carboxy-5,6,7,8-tetrahydropterin + Acetaldehyde + PPPidetails
General function:
Involved in GTP cyclohydrolase I activity
Specific function:
Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.
Gene Name:
GCH1
Uniprot ID:
P30793
Molecular weight:
27902.855
Reactions
Dihydroneopterin triphosphate + Water → 2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidinedetails
General function:
Involved in nucleotide binding
Specific function:
Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity. Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. May also inhibit the transcriptional activity of ATF2.
Gene Name:
RUVBL2
Uniprot ID:
Q9Y230
Molecular weight:
51156.08