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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-05-19 23:44:41 UTC
HMDB IDHMDB0000250
Secondary Accession Numbers
  • HMDB00250
Metabolite Identification
Common NamePyrophosphate
DescriptionThe anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. The pyrophosphate anion is abbreviated PPi and is formed by the hydrolysis of ATP into AMP in cells. This hydrolysis is called pyrophosphorolysis. The pyrophosphate anion has the structure P2O74-, and is an acid anhydride of phosphate. It is unstable in aqueous solution and rapidly hydrolyzes into inorganic phosphate. Pyrophosphate is an osteotoxin (arrests bone development) and an arthritogen (promotes arthritis). It is also a metabotoxin (an endogenously produced metabolite that causes adverse health affects at chronically high levels). Chronically high levels of pyrophosphate are associated with hypophosphatasia. Hypophosphatasia (also called deficiency of alkaline phosphatase or phosphoethanolaminuria) is a rare, and sometimes fatal, metabolic bone disease. Hypophosphatasia is associated with a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP is an enzyme that is tethered to the outer surface of osteoblasts and chondrocytes. TNSALP hydrolyzes several substances, including inorganic pyrophosphate (PPi) and pyridoxal 5'-phosphate (PLP), a major form of vitamin B6. When TSNALP is low, inorganic pyrophosphate (PPi) accumulates outside of cells and inhibits the formation of hydroxyapatite, one of the main components of bone, causing rickets in infants and children and osteomalacia (soft bones) in adults. Vitamin B6 must be dephosphorylated by TNSALP before it can cross the cell membrane. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters which can cause seizures. In some cases, a build-up of calcium pyrophosphate dihydrate crystals in the joints can cause pseudogout.
Structure
Thumb
Synonyms
ValueSource
[(ho)2P(O)OP(O)(OH)2]ChEBI
Acide diphosphoriqueChEBI
DiphosphorsaeureChEBI
H4P2O7ChEBI
PYROphosphATEChEBI
Pyrophosphoric acidChEBI
PyrophosphorsaeureChEBI
Diphosphoric acidGenerator
Chemical FormulaH4O7P2
Average Molecular Weight177.9751
Monoisotopic Molecular Weight177.943225506
IUPAC Name(phosphonooxy)phosphonic acid
Traditional Namepyrophosphoric acid
CAS Registry Number14000-31-8
SMILES
OP(O)(=O)OP(O)(O)=O
InChI Identifier
InChI=1S/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)
InChI KeyXPPKVPWEQAFLFU-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of inorganic compounds known as non-metal pyrophosphates. These are inorganic non-metallic compoundscontaining a pyrophosphate as its largest oxoanion.
KingdomInorganic compounds
Super ClassHomogeneous non-metal compounds
ClassNon-metal oxoanionic compounds
Sub ClassNon-metal pyrophosphates
Direct ParentNon-metal pyrophosphates
Alternative Parents
Substituents
  • Non-metal pyrophosphate
  • Inorganic oxide
  • Acyclic compound
Molecular FrameworkAcyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point61 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
logP-1.4ChemAxon
pKa (Strongest Acidic)1.7ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area124.29 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity25.52 m³·mol⁻¹ChemAxon
Polarizability10.28 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0972000000-a80f120dd426991d6effView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0741900000-9c5b3c334561dd282116View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-03di-0920000000-a5ad76aa129d898d71f8View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-03di-0910000000-531d3e19493dc29d6e5cView in MoNA
GC-MSGC-MS Spectrum - GC-MS (4 TMS)splash10-0udi-0320900000-0abbcb28a43d7e24fe81View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0udi-0320900000-0abbcb28a43d7e24fe81View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-9200000000-47d5c2340766aaf36e95View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004j-5900000000-6633d5123eb37c266247View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0002-9000000000-1274b83242b279e9dac7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-69bc4c795fec87fef4b8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004j-4900000000-fab623ebd43ab1452b9fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-9400000000-b2565f0d436385569cffView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000t-9300000000-ac978f84efc222da7b43View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-21c64963e1ff18b360e1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9700000000-54e41043f009fe6db86cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-2a5f69c16aa671275a62View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
  • Nucleus
  • Endoplasmic reticulum
  • Peroxisome
Biospecimen Locations
  • Blood
  • Saliva
  • Urine
Tissue Locations
  • Epidermis
  • Fibroblasts
  • Intestine
  • Neuron
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Testes
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified1.8 (0.64-2.96) uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Male
Normal
details
UrineDetected and Quantified2.56 +/- 1.22 umol/mmol creatinineChildren (1-13 years old)BothNormal
    • Geigy Scientific ...
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID996
KEGG Compound IDC00013
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPyrophosphate
METLIN IDNot Available
PubChem Compound1023
PDB IDPPV
ChEBI ID29888
References
Synthesis ReferenceDittmer, Donald C.; Silverstein, V. Opshelor. Production of pyrophosphate from S-n-butyl phosphorothioate. Journal of Organic Chemistry (1961), 26 4706-7.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634 ]
  2. 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 ]
  3. Broll H: [Effect of chloroquine diphosphate on the superhelix structure of DNA and protein synthesis in synovial cells in chronic polyarthritis]. Wien Klin Wochenschr. 1983 Dec 23;95(24):877-80. [PubMed:6670282 ]
  4. Golanski J, Pluta J, Baraniak J, Watala C: Limited usefulness of the PFA-100 for the monitoring of ADP receptor antagonists--in vitro experience. Clin Chem Lab Med. 2004 Jan;42(1):25-9. [PubMed:15061376 ]
  5. Mateos-Trigos G, Evans RJ, Heath MF: Effects of P2Y(1) and P2Y(12) receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets. Platelets. 2002 Aug-Sep;13(5-6):285-92. [PubMed:12189014 ]
  6. Sirkis SI: [Serum and cerebrospinal fluid enzyme spectra in meningitis and their differential diagnostic value]. Zh Nevropatol Psikhiatr Im S S Korsakova. 1982;82(2):193-7. [PubMed:7072418 ]
  7. Barbier O, Torra IP, Sirvent A, Claudel T, Blanquart C, Duran-Sandoval D, Kuipers F, Kosykh V, Fruchart JC, Staels B: FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Gastroenterology. 2003 Jun;124(7):1926-40. [PubMed:12806625 ]
  8. March JG, Simonet BM, Grases F: Determination of pyrophosphate in renal calculi and urine by means of an enzymatic method. Clin Chim Acta. 2001 Dec;314(1-2):187-94. [PubMed:11718694 ]
  9. Namiki M, Kitamura M, Nonomura N, Sugao H, Nakamura M, Okuyama A, Utsunomiya M, Itatani H, Matsumoto K, Sonoda T: Direct inhibitory effect of estrogen on the human testis in vitro. Arch Androl. 1988;20(2):131-5. [PubMed:3395157 ]
  10. Pickett DA, Welch DF: Recognition of Staphylococcus saprophyticus in urine cultures by screening colonies for production of phosphatase. J Clin Microbiol. 1985 Mar;21(3):310-3. [PubMed:2984240 ]
  11. Hua HT, Albadawi H, Entabi F, Conrad M, Stoner MC, Meriam BT, Sroufe R, Houser S, Lamuraglia GM, Watkins MT: Polyadenosine diphosphate-ribose polymerase inhibition modulates skeletal muscle injury following ischemia reperfusion. Arch Surg. 2005 Apr;140(4):344-51; discussion 351-2. [PubMed:15837884 ]
  12. Dahlmann N, Ueckermann C: Separation of deoxythymidine-5'-triphosphatase from unspecific hydrolases. A recommended micromethod in the diagnostic evaluation of human carcinoma. Anticancer Res. 1984 Jul-Oct;4(4-5):299-303. [PubMed:6091528 ]
  13. Ebadi M, Sharma SK, Ghafourifar P, Brown-Borg H, El Refaey H: Peroxynitrite in the pathogenesis of Parkinson's disease and the neuroprotective role of metallothioneins. Methods Enzymol. 2005;396:276-98. [PubMed:16291239 ]
  14. Tallaksen CM, Sande A, Bohmer T, Bell H, Karlsen J: Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally. Eur J Clin Pharmacol. 1993;44(1):73-8. [PubMed:8436160 ]
  15. Zhong D, Meins J, Scheidel B, Blume H: [Development of an HPLC method for determination of chloroquine in plasma]. Pharmazie. 1993 May;48(5):349-52. [PubMed:8327563 ]
  16. Recio JA, Paez JG, Maskeri B, Loveland M, Velasco JA, Notario V: Both normal and transforming PCPH proteins have guanosine diphosphatase activity but only the oncoprotein cooperates with Ras in activating extracellular signal-regulated kinase ERK1. Cancer Res. 2000 Mar 15;60(6):1720-8. [PubMed:10749145 ]
  17. Puri RN, Colman RF, Colman RW: Modulation of platelet responses by 2-[3-(bromo-2-oxopropylthio)]adenosine-5'-diphosphate involves its binding to as well as covalent modification of an ADP-receptor, aggregin. Arch Biochem Biophys. 1997 Jul 1;343(1):140-5. [PubMed:9210656 ]
  18. Hamagishi Y, Oki T, Tone H, Inui T: A radioimmunoassay for guanosine-5'-diphosphate-3'-diphosphate and adenosine-5'-triphosphate-3'-diphosphate. J Biochem. 1980 Dec;88(6):1785-92. [PubMed:6780546 ]
  19. Lee AY, Youm YH, Kim NH, Yang H, Choi WI: Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis. Br J Dermatol. 2004 Nov;151(5):995-1003. [PubMed:15541077 ]
  20. Ito H, Yamamoto H, Kimura Y, Kambe H, Okochi T, Kishimoto S: Affinity chromatography of human plasma gelsolin with polyphosphate compounds on immobilized Cibacron Blue F3GA. J Chromatogr. 1990 Apr 6;526(2):397-406. [PubMed:2163407 ]

Only showing the first 10 proteins. There are 351 proteins in total.

Enzymes

General function:
Involved in acetate-CoA ligase activity
Specific function:
Activates acetate so that it can be used for lipid synthesis or for energy generation.
Gene Name:
ACSS2
Uniprot ID:
Q9NR19
Molecular weight:
78579.11
Reactions
Adenosine triphosphate + Acetic acid + Coenzyme A → Adenosine monophosphate + Pyrophosphate + Acetyl-CoAdetails
Adenosine triphosphate + Acetic acid → Pyrophosphate + Acetyl adenylatedetails
Adenosine triphosphate + Propionic acid → Pyrophosphate + Propinol adenylatedetails
General function:
Involved in acetate-CoA ligase activity
Specific function:
Important for maintaining normal body temperature during fasting and for energy homeostasis. Essential for energy expenditure under ketogenic conditions (By similarity). Converts acetate to acetyl-CoA so that it can be used for oxidation through the tricarboxylic cycle to produce ATP and CO(2).
Gene Name:
ACSS1
Uniprot ID:
Q9NUB1
Molecular weight:
74625.88
Reactions
Adenosine triphosphate + Acetic acid + Coenzyme A → Adenosine monophosphate + Pyrophosphate + Acetyl-CoAdetails
Adenosine triphosphate + Acetic acid → Pyrophosphate + Acetyl adenylatedetails
Adenosine triphosphate + Propionic acid → Pyrophosphate + Propinol adenylatedetails
General function:
Involved in arylesterase activity
Specific function:
Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents.
Gene Name:
PON3
Uniprot ID:
Q15166
Molecular weight:
39607.185
General function:
Involved in fucose-1-phosphate guanylyltransferase acti
Specific function:
Catalyzes the formation of GDP-L-fucose from GTP and L-fucose-1-phosphate. Functions as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids.
Gene Name:
FPGT
Uniprot ID:
O14772
Molecular weight:
37630.405
Reactions
Guanosine triphosphate + Fucose 1-phosphate → Pyrophosphate + GDP-L-fucosedetails
General function:
Involved in transferase activity
Specific function:
Not Available
Gene Name:
FDFT1
Uniprot ID:
P37268
Molecular weight:
48114.87
Reactions
Farnesyl pyrophosphate + NAD(P)H → Squalene + Pyrophosphate + NAD(P)(+)details
Farnesyl pyrophosphate → Pyrophosphate + Presqualene diphosphatedetails
Presqualene diphosphate + NADPH + Hydrogen Ion → Pyrophosphate + Squalene + NADPdetails
Farnesyl pyrophosphate + NADPH + Hydrogen Ion → Squalene + Pyrophosphate + NADPdetails
General function:
Involved in nucleotide binding
Specific function:
Not Available
Gene Name:
FARSA
Uniprot ID:
Q9Y285
Molecular weight:
57563.225
Reactions
Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) → Adenosine monophosphate + Pyrophosphate + L-phenylalanyl-tRNA(Phe)details
Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) → Adenosine monophosphate + Pyrophosphate + L-Phenylalanyl-tRNA(Phe)details
General function:
Involved in nucleotide binding
Specific function:
Catalyzes direct attachment of p-Tyr (Tyr) to tRNAPhe. Permits also, with a lower efficiency, the attachment of m-Tyr to tRNAPhe, thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins.
Gene Name:
FARS2
Uniprot ID:
O95363
Molecular weight:
52356.21
Reactions
Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) → Adenosine monophosphate + Pyrophosphate + L-phenylalanyl-tRNA(Phe)details
Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) → Adenosine monophosphate + Pyrophosphate + L-Phenylalanyl-tRNA(Phe)details
General function:
Involved in oxidoreductase activity
Specific function:
Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.
Gene Name:
ALDH7A1
Uniprot ID:
P49419
Molecular weight:
58486.74
Reactions
Aminoadipic acid + Adenosine triphosphate → L-2-Aminoadipate adenylate + Pyrophosphatedetails
General function:
Involved in amidophosphoribosyltransferase activity
Specific function:
Not Available
Gene Name:
PPAT
Uniprot ID:
Q06203
Molecular weight:
57398.52
Reactions
5-Phosphoribosylamine + Pyrophosphate + L-Glutamic acid → L-Glutamine + Phosphoribosyl pyrophosphate + Waterdetails
General function:
Involved in nucleotidyltransferase activity
Specific function:
Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, prefers NAD(+) and NAAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following mechanical or toxic insults.
Gene Name:
NMNAT1
Uniprot ID:
Q9HAN9
Molecular weight:
31932.22
Reactions
Adenosine triphosphate + beta-nicotinamide D-ribonucleotide → Pyrophosphate + NADdetails
Adenosine triphosphate + beta-nicotinate-D-ribonucleotide → Pyrophosphate + Nicotinic acid adenine dinucleotidedetails
Adenosine triphosphate + nicotinate beta-D-ribonucleotide → Pyrophosphate + Nicotinic acid adenine dinucleotidedetails

Only showing the first 10 proteins. There are 351 proteins in total.