View source for Pyrophosphate

{{Short description|Class of chemical compounds}}
{{Hatnote|"Diphosphate" redirects here. It can also refer to any salt containing two [[phosphate]] groups.}}
{{Chembox
| verifiedrevid = 1276963742
| ImageFile = Pyrophosphate_anion.png
| ImageFile1 = Pyrophosphate-3D-balls.png
| ImageAlt1 = 
| ImageCaption1 = {{legend|orange|[[Phosphorus]], P}}{{legend|red|[[Oxygen]], O}}
| ImageName1 = Pyrophosphate anion
| IUPACName = Diphosphate
| SystematicName = Dipolyphosphate
| OtherNames = Pyrophosphate<br/>Phosphonatophosphate
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 14000-31-8
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo2 = 13472-36-1
| CASNo2_Comment = (tetrasodium decahydrate salt)
| CASNo3_Ref = {{cascite|correct|CAS}}
| CASNo3 = 7758-16-9
| CASNo3_Comment = (disodium salt)
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 18361
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 559142
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB04160
| KEGG = 
| Gmelin = 26938
| UNII = X3SSV2V6L3
| InChI = 1/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)/p-4
| InChIKey = XPPKVPWEQAFLFU-XBHQNQODAI
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)/p-4
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XPPKVPWEQAFLFU-UHFFFAOYSA-J
| PubChem = 644102
| SMILES = [O-]P(=O)([O-])OP(=O)([O-])[O-]
}}
|Section2={{Chembox Properties
| Formula = {{chem2|P2O7(4-)}}
| P=2|O=7
| ConjugateAcid = [[Pyrophosphoric acid]]
}}
|Section3={{Chembox Hazards
| MainHazards = 
}}
}}
In [[chemistry]], '''pyrophosphates''' are [[phosphorus]] [[oxyanion]]s that contain two phosphorus atoms in a {{chem2|P\sO\sP}} linkage. A number of pyrophosphate salts exist, such as [[disodium pyrophosphate]] ({{chem2|Na2H2P2O7}}) and [[tetrasodium pyrophosphate]] ({{chem2|Na4P2O7}}), among others. Often pyrophosphates are called '''diphosphates'''. The parent pyrophosphates are derived from partial or complete neutralization of [[pyrophosphoric acid]]. The '''pyrophosphate bond''' is also sometimes referred to as a phosphoanhydride bond, a naming convention which emphasizes the loss of water that occurs when two phosphates form a new {{chem2|P\sO\sP}} bond, and which mirrors the nomenclature for [[Organic acid anhydride|anhydrides of carboxylic acids]]. Pyrophosphates are found in [[Adenosine triphosphate|ATP]] and other [[nucleotide]] triphosphates, which are important in biochemistry. The term pyrophosphate is also the name of [[ester]]s formed by the condensation of a phosphorylated biological compound with [[inorganic phosphate]], as for [[dimethylallyl pyrophosphate]]. This bond is also referred to as a [[high-energy phosphate]] bond.

==Acidity==
Pyrophosphoric acid is a tetraprotic acid, with four distinct [[pKa|p''K''<sub>a</sub>]]'s:<ref>{{cite journal |doi=10.1039/d1qi00209k|title=Induced fit activity-based sensing: A mechanistic study of pyrophosphate detection with a "flexible" Fe-salen complex |year=2021 |last1=Yadav |first1=Prerna |last2=Blacque |first2=Olivier |last3=Roodt |first3=Andreas |last4=Zelder |first4=Felix |journal=Inorganic Chemistry Frontiers |volume=8 |issue=19 |pages=4313–4323 |pmid=34603734 |pmc=8477187 }}</ref>
:{{chem2|H4P2O7 ⇌ [H3P2O7]− + H+}}, p''K''<sub>a1</sub> = 0.85
:{{chem2|[H3P2O7]− ⇌ [H2P2O7](2−) + H+}}, p''K''<sub>a2</sub> = 1.96 
:{{chem2|[H2P2O7](2−) ⇌ [HP2O7](3−) + H+}}, p''K''<sub>a3</sub> = 6.60
:{{chem2|[HP2O7](3−) ⇌ [P2O7](4−) + H+}}, p''K''<sub>a4</sub> = 9.41 
The pKa's occur in two distinct ranges because deprotonations occur on separate phosphate groups. For comparison with the p''K''<sub>a</sub>s for [[phosphoric acid]] are 2.14, 7.20, and 12.37.

At physiological [[pH]]s, pyrophosphate exists as a mixture of doubly and singly protonated forms.

==Preparation==
Disodium pyrophosphate is prepared by thermal condensation of [[sodium dihydrogen phosphate]] or by partial deprotonation of pyrophosphoric acid.<ref>{{cite book |doi=10.1002/9780470132340.ch24|chapter=Sodium Pyrophosphates (Sodium Diphosphates) |year=1950 |last1=Bell |first1=R. N.|title=Inorganic Syntheses |pages=98–101 |isbn=9780470132340|volume=3 }}</ref>

Pyrophosphates are generally white or colorless. The [[alkali metal]] salts are water-soluble.<ref>C.Michael Hogan. 2011. [http://www.eoearth.org/article/Phosphate?topic=49557 ''Phosphate''. Encyclopedia of Earth. Topic ed. Andy Jorgensen. Ed.-in-Chief C.J.Cleveland. National Council for Science and the Environment. Washington DC]</ref> They are good complexing agents for metal ions (such as calcium and many transition metals) and have many uses in industrial chemistry. Pyrophosphate is the first member of an entire series of [[polyphosphate]]s.<ref>{{Greenwood&Earnshaw2nd}}</ref>

== Biochemistry ==
The anion {{chem2|P2O7(4−)}} is abbreviated '''PP<sub>i</sub>''', standing for '''''i'''norganic '''p'''yro'''p'''hosphate''. It is formed by the [[hydrolysis]] of [[Adenosine triphosphate|ATP]] into [[Adenosine monophosphate|AMP]] in [[Cell (biology)|cells]].
:ATP → AMP + PP<sub>i</sub>

For example, when a nucleotide is incorporated into a growing [[DNA]] or [[RNA]] strand by a [[polymerase]], pyrophosphate (PP<sub>i</sub>) is released. Pyrophosphorolysis is the reverse of the [[polymerization]] reaction in which pyrophosphate reacts with the 3′-nucleosidemonophosphate ([[Nucleoside triphosphate|NMP]] or dNMP), which is removed from the [[oligonucleotide]] to release the corresponding triphosphate ([[nucleoside triphosphate|dNTP]] from DNA, or [[nucleoside triphosphate|NTP]] from RNA).

The pyrophosphate anion has the structure {{chem2|P2O7(4−)}}, and is an [[acid anhydride]] of [[phosphate]]. It is unstable in [[aqueous solution]] and [[hydrolysis|hydrolyze]]s into inorganic phosphate:
:{{chem2|P2O7(4−) + H2O → 2 HPO4(2−)}}
or in biologists' shorthand notation:
:{{chem2|PP_{i} + H2O → 2 P_{i} + 2 H+}}

In the absence of enzymic catalysis, hydrolysis reactions of simple polyphosphates such as pyrophosphate, linear triphosphate, [[Adenosine diphosphate|ADP]], and ATP normally proceed extremely slowly in all but highly acidic media.<ref name="Wazer">{{ cite journal |vauthors=Van Wazer JR, Griffith EJ, McCullough JF |title=Structure and Properties of the Condensed Phosphates. VII. Hydrolytic Degradation of Pyro- and Tripolyphosphate |journal=J. Am. Chem. Soc. |date=Jan 1955 |volume=77 |issue=2 |pages=287–291 |doi=10.1021/ja01607a011|bibcode=1955JAChS..77..287V }}</ref>

(The reverse of this reaction is a method of preparing pyrophosphates by heating phosphates.)

This hydrolysis to inorganic phosphate effectively renders the cleavage of ATP to AMP and PP<sub>i</sub> [[hydrolysis|irreversible]], and biochemical reactions coupled to this hydrolysis are irreversible as well.

From the standpoint of [[high energy phosphate]] accounting, the hydrolysis of ATP to AMP and PP<sub>i</sub> requires two high-energy phosphates, as to reconstitute AMP into ATP requires two [[phosphorylation]] reactions.
:AMP + ATP → 2 [[Adenosine diphosphate|ADP]]
:2 ADP + 2 P<sub>i</sub> → 2 ATP

The plasma concentration of inorganic pyrophosphate has a reference range of 0.58–3.78&nbsp;[[Molarity|μM]] (95% prediction interval).<ref>{{cite journal |vauthors=Ryan LM, Kozin F, McCarty DJ |title=Quantification of human plasma inorganic pyrophosphate. I. Normal values in osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease |journal=Arthritis Rheum. |volume=22 |issue=8 |pages=886–91 |year=1979 |pmid=223577 |doi= 10.1002/art.1780220812 |doi-access=}}</ref>

===Terpenes===
[[Isopentenyl pyrophosphate]] converts to [[geranyl pyrophosphate]], the precursor to tens of thousands of [[terpene|terpenes]]s and [[terpenoid|terpenoids]].<ref>{{cite book|title=Terpenes: Flavors, Fragrances, Pharmaca, Pheromones|url=https://archive.org/details/terpenes00brei|url-access=limited|pages=[https://archive.org/details/terpenes00brei/page/n18 10]–23|chapter=Hemi- and Monoterpenes|author=Eberhard Breitmaier|year= 2006|doi=10.1002/9783527609949.ch2|isbn=9783527609949}}</ref><ref name=KO>{{cite book |doi=10.1002/0471238961.2005181602120504.a01.pub2|chapter=Terpenoids |title=Kirk-Othmer Encyclopedia of Chemical Technology |year=2006 |last1=Sell |first1=Charles S. |isbn=0471238961 }}</ref> 
[[Image:Synthesis of geranyl pyrophosphate.png|thumb|center|400px|[[Isopentenyl pyrophosphate]] (IPP) and [[dimethylallyl pyrophosphate]] (DMAPP) condense to produce [[geranyl pyrophosphate]], precursor to all terpenes and terpenoids.]]

== Physiological role ==

=== Hydroxyapetite precipitation inhibitor ===
PP<sub>i</sub> is an important inhibitor of [[hydroxyapatite]] precipitation present in [[Extracellular fluid|extracellular fluid (ECF)]] (including [[blood plasma]],<ref name=":02">{{Cite book |last=Hall |first=John E. |title=Guyton and Hall Textbook of Medical Physiology |last2=Hall |first2=Michael E. |date= |publisher=Elsevier |year=2021 |isbn=978-0-323-59712-8 |edition=14th |location=Philadelphia, PA |pages=994-995 |chapter=Chapter 55 - Spinal Cord Motor Functions; the Cord Reflexes}}</ref> [[synovial fluid]], and [[urine]].<ref name="Ho">{{cite journal |vauthors=Ho AM, Johnson MD, Kingsley DM |date=Jul 2000 |title=Role of the mouse ank gene in control of tissue calcification and arthritis |journal=Science |volume=289 |issue=5477 |pages=265–70 |bibcode=2000Sci...289..265H |doi=10.1126/science.289.5477.265 |pmid=10894769}}</ref>{{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=June 2025}}). ECF is [[Supersaturation|supersaturated]] in Ca<sup>2+</sup> and PO<sub>4</sub><sup>3-</sup> ions - in other words, the concentration of these ions is far in excess of the limit beyond which hydroxyapetite crystals would normally begin to precipitate from the solution (a pathological condition known as [[metastatic calcification]]).<ref name=":02" />

==== Regulation ====
The levels of PP<sub>i</sub> are regulated by at least three molecules - notably [[Tissue-nonspecific alkaline phosphatase|tissue-nonspecific alkaline phosphatase (TNAP)]] which is secreted by [[Osteoblast|osteoblasts]] locally into the [[osteoid]] to degrade PP<sub>i</sub> and thus allow [[bone mineralization]] to proceed during bone growth or [[Bone remodeling|remodeling]]. Congenital deficiency of TNAP in animal models results in offspring with soft, inadequately calcified bones.<ref name=":02" />

Osteoblasts also secrete [[Nucleotide pyrophosphatase/phosphodiesterase|nucleotide pyrophosphatase phosphodiesterase 1 (NPP1)]] which causes extracellular PP<sub>i</sub> production, and [[ANKH|progressive ankylosis protein homolog (ANK)]] which promotes PP<sub>i</sub> transport out of cells. Deficiencies of NPP1 and ANK result in deficient extracellular PP<sub>i</sub> concentrations and are clinically associated with [[metastatic calcification]] and excessive calcification of bone (manifesting clinically e.g. as [[Osteophyte|osteophytes]]).<ref name=":02" />

=== Research ===
Cells may channel intracellular PP<sub>i</sub> into ECF.<ref name="Rutsch">{{cite journal |vauthors=Rutsch F, Vaingankar S, Johnson K, Goldfine I, Maddux B, Schauerte P, Kalhoff H, Sano K, Boisvert WA, Superti-Furga A, Terkeltaub R |date=Feb 2001 |title=PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification |journal=Am J Pathol |volume=158 |issue=2 |pages=543–54 |doi=10.1016/S0002-9440(10)63996-X |pmc=1850320 |pmid=11159191}}</ref>{{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=June 2025}} [[ANKH|ANK]] is a non-enzymatic plasma-membrane PP<sub>i</sub> channel that supports extracellular PP<sub>i</sub> levels.<ref name="Rutsch" />{{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=June 2025}} Defective function of the membrane PP<sub>i</sub> channel ANK is associated with low extracellular PP<sub>i</sub> and elevated intracellular PP<sub>i</sub>.<ref name="Ho" /> [[Ectonucleotide pyrophosphatase/phosphodiesterase 1|Ectonucleotide pyrophosphatase/phosphodiesterase]] (ENPP) may function to raise extracellular PP<sub>i</sub>.<ref name="Rutsch" />{{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=June 2025}}

==As a food additive==<!-- linked from redirect [[E450 (food additive)]] -->

Various diphosphates are used as [[emulsifier]]s, [[stabiliser (food)|stabiliser]]s, [[acidity regulator]]s, [[raising agent]]s, [[sequestrant]]s, and [[water retention agent]]s in food processing.<ref>''[[Codex Alimentarius]]'' '''1A''', 2nd ed, 1995, pp. 71, 82, 91</ref> They are classified in the [[E number]] scheme under E450:<ref>D. J. Jukes, ''Food Legislation of the UK: A Concise Guide'', Elsevier, 2013, p. 60–61</ref>

*E450(a): [[disodium pyrophosphate|''di''sodium dihydrogen diphosphate]]; ''tri''sodium diphosphate; [[tetrasodium pyrophosphate|''tetra''sodium diphosphate]] (TSPP); tetrapotassium diphosphate
*E450(b): ''penta''sodium and ''penta''potassium triphosphate
*E450(c): sodium and potassium polyphosphates

In particular, various formulations of diphosphates are used to stabilize [[whipped cream]].<ref>Ricardo A. Molins, ''Phosphates in Food'', p. 115</ref>

== See also ==
{{div col|colwidth=12em}}
* [[Adenosine monophosphate]]
* [[Adenosine diphosphate]]
* [[Adenosine triphosphate]]
* [[ATPase]]
* [[ATP hydrolysis]]
* [[ATP synthase]]
* [[Biochemistry]]
* [[Bone]]
* [[Calcium pyrophosphate]]
* [[Calcium pyrophosphate dihydrate deposition disease]]
* [[Catalysis]]
* [[DNA]]
* [[High energy phosphate]]
* [[Inorganic pyrophosphatase]]
* [[Nucleoside triphosphate]]
* [[Nucleotide]]
* [[Organophosphate]]
* [[Oxidative phosphorylation]]
* [[Phosphate]]
* [[Phosphoric acid]]
* [[Phosphoric acids and phosphates]]
* [[RNA]]
* [[Sodium pyrophosphate]]
* [[Superphosphate]]
* [[Thiamine pyrophosphate]]
* [[Tooth]]
* [[Zinc pyrophosphate]]
{{Div col end}}

==References==
{{Reflist}}

==Further reading==
* {{cite journal |vauthors=Schröder HC, Kurz L, Muller WE, Lorenz B |title=Polyphosphate in bone |journal=Biochemistry (Moscow) |date=Mar 2000 |volume=65 |issue=3 |pages=296–303 |pmid=10739471 |url=http://protein.bio.msu.su/biokhimiya/contents/v65/pdf/bcm_0296.pdf |url-status=dead |archive-url=https://web.archive.org/web/20110825053648/http://protein.bio.msu.su/biokhimiya/contents/v65/pdf/bcm_0296.pdf |archive-date=2011-08-25}}

==External links==
{{Wiktionary|diphosphate|pyrophosphate}}
*{{Commons category-inline|Pyrophosphates}}
*{{MeshName|Pyrophosphates}}

{{Phosphorus compounds}}

[[Category:Pyrophosphates| ]]
[[Category:Anions]]
[[Category:Dietary minerals]]
[[Category:Molecular biology]]
[[Category:Nucleotides]]
[[Category:E-number additives]]