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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-02-26 21:23:00 UTC
HMDB IDHMDB0001155
Secondary Accession Numbers
  • HMDB0001435
  • HMDB01155
  • HMDB01435
Metabolite Identification
Common NameDiadenosine triphosphate
DescriptionDiadenosine triphosphate (AP3A) is a diadenosine polyphosphate. Diadenosine polyphosphates (APnAs, n = 3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. APnAs have been demonstrated to be involved in the control of vascular tone as well as the growth of vascular smooth muscle cells and hence, possibly, in atherogenesis. APnAs isolated substances are Ap3A, Ap4A, Ap5A, and Ap6A. APnAs are naturally occurring substances that facilitate tear secretion; they are released from the corneal epithelium, they stimulate tear production and therefore they may be considered as physiological modulators of tear secretion. The APnAs were discovered in the mid-sixties in the course of studies on aminoacyl-tRNA synthetases (aaRS). APnAs have emerged as intracellular and extracellular signalling molecules implicated in the maintenance and regulation of vital cellular functions and become considered as second messengers. Great variety of physiological and pathological effects in mammalian cells was found to be associated with alterations of APnAs. APnAs are polyphosphated nucleotidic substances which are found in the CNS and are known to be released in a calcium-dependent manner from storage vesicles in brain synaptosomes. AP3A is a primer for oligoadenylate synthesis catalyzed by interferon-inducible 2-5A synthetase. AP3A is synthesized in cells by tryptophanyl-tRNA synthetase (WRS); cellular level of AP3A significantly increases after interferon treatment. AP3A is an avid inhibitor of eosinophil-derived neurotoxin (EDN). EDN is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. AP3A accumulates in cells in response to various physiological factors. AP3A FHIT (Fragile histidine Triad) is a human tumor suppressor gene. The Fhit protein is believed to inhibit tumor growth by inducing apoptosis through interaction with AP3A. (PMID: 11212966 , 12738682 , 11810214 , 9607303 , 8922753 , 9187362 , 16401072 , 12833632 , 11896678 ).
Structure
Data?1582752180
Synonyms
ValueSource
Diadenosine triphosphoric acidGenerator
Adenosine (5')triphospho(5')adenosineHMDB
Adenosine 5'-triphosphate 5'-adenosineHMDB
Adenosine(3)triphosphate adenosineHMDB
Adenosine(5')triphospho(5')adenosineHMDB
Bis(adenosine)-5'-triphosphateHMDB
p(1),p(3)-Bis(5'-adenosyl) trihydrogen triphosphateHMDB
p(1),p(3)-Bis(5'-adenosyl) triphosphateHMDB
p(1)-p(3)-Bis(5'-adenosyl) triphosphateHMDB
P1,P3-Bis(5'-adenosyl) triphosphateHMDB
Ap3aHMDB
5'Ap3aHMDB
p(1),(P3)-Bis(5'-adenosyl)triphosphateHMDB
ApppAHMDB
Chemical FormulaC20H27N10O16P3
Average Molecular Weight756.4071
Monoisotopic Molecular Weight756.081934402
IUPAC Name{[(2S,3R,4S,5S)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphinic acid
Traditional Name[(2S,3R,4S,5S)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy({[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxy(hydroxy)phosphoryl)oxyphosphinic acid
CAS Registry Number56432-02-1
SMILES
NC1=C2N=CN([C@H]3O[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]4O[C@H]([C@H](O)[C@@H]4O)N4C=NC5=C(N)N=CN=C45)[C@H](O)[C@@H]3O)C2=NC=N1
InChI Identifier
InChI=1S/C20H27N10O16P3/c21-15-9-17(25-3-23-15)29(5-27-9)19-13(33)11(31)7(43-19)1-41-47(35,36)45-49(39,40)46-48(37,38)42-2-8-12(32)14(34)20(44-8)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-34H,1-2H2,(H,35,36)(H,37,38)(H,39,40)(H2,21,23,25)(H2,22,24,26)/t7-,8+,11-,12+,13-,14+,19-,20+
InChI KeyQCICUPZZLIQAPA-WGIMJHEJSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as (5'->5')-dinucleotides. These are dinucleotides where the two bases are connected via a (5'->5')-phosphodiester linkage.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
Class(5'->5')-dinucleotides
Sub ClassNot Available
Direct Parent(5'->5')-dinucleotides
Alternative Parents
Substituents
  • (5'->5')-dinucleotide
  • Purine ribonucleoside triphosphate
  • Purine nucleotide sugar
  • Purine ribonucleoside monophosphate
  • Pentose phosphate
  • Pentose-5-phosphate
  • Glycosyl compound
  • N-glycosyl compound
  • 6-aminopurine
  • Monosaccharide phosphate
  • Purine
  • Imidazopyrimidine
  • Monoalkyl phosphate
  • Aminopyrimidine
  • Alkyl phosphate
  • Monosaccharide
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Pyrimidine
  • Phosphoric acid ester
  • Imidolactam
  • Tetrahydrofuran
  • Imidazole
  • Azole
  • Heteroaromatic compound
  • Secondary alcohol
  • Azacycle
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Alcohol
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Amine
  • Primary amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Biological location:

Source:

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 Solubility4.39 g/LALOGPS
logP-1.3ALOGPS
logP-9.1ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)0.91ChemAxon
pKa (Strongest Basic)5.29ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count20ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area387.44 ŲChemAxon
Rotatable Bond Count12ChemAxon
Refractivity155.23 m³·mol⁻¹ChemAxon
Polarizability62.1 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ab9-1211090100-8dd4ac3e3f704ce81480Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0910100300-a4645b9f9e4bff03904aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-9d576618c3405dd82c62Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0900000000-d874a1705ef911a68a3fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a59-0700110900-6003bb661e58b16c00f0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-0900100000-cc9f72dc9a076e69680cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001r-1940100000-375a011d350537091bbbSpectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
Tissue LocationsNot Available
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.85 +/- 0.32 uMAdult (>18 years old)BothHemodialysis details
Associated Disorders and Diseases
Disease References
Hemodialysis
  1. Jankowski J, Jankowski V, Laufer U, van der Giet M, Henning L, Tepel M, Zidek W, Schluter H: Identification and quantification of diadenosine polyphosphate concentrations in human plasma. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1231-8. Epub 2003 May 8. [PubMed:12738682 ]
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022454
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDC06197
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound14464643
PDB IDNot Available
ChEBI ID27775
Food Biomarker OntologyNot Available
VMH IDM01360
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Hollah P, Hausberg M, Kosch M, Barenbrock M, Letzel M, Schlatter E, Rahn KH: A novel assay for determination of diadenosine polyphosphates in human platelets: studies in normotensive subjects and in patients with essential hypertension. J Hypertens. 2001 Feb;19(2):237-45. [PubMed:11212966 ]
  2. Jankowski J, Jankowski V, Laufer U, van der Giet M, Henning L, Tepel M, Zidek W, Schluter H: Identification and quantification of diadenosine polyphosphate concentrations in human plasma. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1231-8. Epub 2003 May 8. [PubMed:12738682 ]
  3. Pintor J, Carracedo G, Alonso MC, Bautista A, Peral A: Presence of diadenosine polyphosphates in human tears. Pflugers Arch. 2002 Jan;443(3):432-6. Epub 2001 Aug 23. [PubMed:11810214 ]
  4. Kisselev LL, Justesen J, Wolfson AD, Frolova LY: Diadenosine oligophosphates (Ap(n)A), a novel class of signalling molecules? FEBS Lett. 1998 May 8;427(2):157-63. [PubMed:9607303 ]
  5. Pintor J, King BF, Miras-Portugal MT, Burnstock G: Selectivity and activity of adenine dinucleotides at recombinant P2X2 and P2Y1 purinoceptors. Br J Pharmacol. 1996 Nov;119(5):1006-12. [PubMed:8922753 ]
  6. Turpaev K, Hartmann R, Kisselev L, Justesen J: Ap3A and Ap4A are primers for oligoadenylate synthesis catalyzed by interferon-inducible 2-5A synthetase. FEBS Lett. 1997 May 19;408(2):177-81. [PubMed:9187362 ]
  7. Baker MD, Holloway DE, Swaminathan GJ, Acharya KR: Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A. Biochemistry. 2006 Jan 17;45(2):416-26. [PubMed:16401072 ]
  8. Vartanian AA: Gelsolin and plasminogen activator inhibitor-1 are Ap3A-binding proteins. Ital J Biochem. 2003 Mar;52(1):9-16. [PubMed:12833632 ]
  9. Kowara R, Karaczyn AA, Fivash MJ Jr, Kasprzak KS: In vitro inhibition of the enzymatic activity of tumor suppressor FHIT gene product by carcinogenic transition metals. Chem Res Toxicol. 2002 Mar;15(3):319-25. [PubMed:11896678 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.
Gene Name:
FHIT
Uniprot ID:
P49789
Molecular weight:
16858.11
Reactions
Diadenosine triphosphate + Water → ADP + Adenosine monophosphatedetails