View source for Adenosine triphosphate

{{Short description|Energy-carrying molecule in living cells}}
{{chembox
| Watchedfields  = changed
| verifiedrevid  = 477228486
| Name           = Adenosine-5'-triphosphate
| ImageFile      = Adenosintriphosphat protoniert.svg
| ImageSize      = 280px
| ImageClass     = skin-invert-image
| ImageFileL1    = ATP-xtal-3D-balls.png
| ImageFileR1    = ATP-xtal-3D-vdW.png
| OtherNames     =
| IUPACName      = Adenosine 5′-(tetrahydrogen triphosphate)
| SystematicName = ''O''<sup>1</sup>-<nowiki/>{[(2''R'',3''S'',4''R'',5''R'')-5-(6-Amino-9''H''-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl} tetrahydrogen triphosphate
| Section1       = {{Chembox Identifiers
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00171
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 15422
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00002
| SMILES = O=P(O)(O)OP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)[C@H](O)[C@@H]3O
| InChIKey = ZKHQWZAMYRWXGA-KQYNXXCUBG
| PubChem = 5957
| IUPHAR_ligand = 1713
| SMILES1 = c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZKHQWZAMYRWXGA-KQYNXXCUSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 56-65-5
| CASNo_Comment = (free acid)
| CASNo2_Ref = {{cascite|unknown|CAS}}
| CASNo2 = 34369-07-8
| CASNo2_Comment = (disodium salt hydrate)
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8L70Q75FXE
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 14249
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5742
 }}
| Section2       = {{Chembox Properties
|   C=10|H=16|N=5|O=13|P=3
|   MolarMass = 507.18 g/mol
|   MeltingPtC = 187
|   MeltingPt_notes = disodium&nbsp;salt; decomposes
|   Density = 1.04 g/cm<sup>3</sup> (disodium salt)
|   pKa = 0.9, 1.4, 3.8, 6.5
| LambdaMax = 259 nm<ref name="lamda_source_1">{{cite web |title=Adenosine 5'-triphosphate disodium salt Product Information |url=https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/a7699pis.pdf |publisher=Sigma |access-date=2019-03-22 |archive-url=https://web.archive.org/web/20190323054630/https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/a7699pis.pdf |archive-date=2019-03-23 |url-status=live }}</ref>
| Absorbance = [[Molar attenuation coefficient|ε<sub>259</sub>]] = 15.4 mM<sup>−1</sup> cm<sup>−1</sup> <ref name="lamda_source_1" />
 }}
| Section3       =
| Section4       =
| Section5       =
| Section6       =
}}
[[File:AdenosineTriphosphate.qutemol.svg|alt=A chemical formula|thumb|Interactive animation of the structure of ATP]]

'''Adenosine triphosphate''' ('''ATP''') is a [[nucleoside triphosphate]]<ref>{{cite journal |last1=Dunn |first1=Jacob |last2=Grider |first2=Michael H. |title=Physiology, Adenosine Triphosphate |url=https://www.ncbi.nlm.nih.gov/books/NBK553175/ |website=StatPearls |publisher=StatPearls Publishing |access-date=13 November 2023 |date=2023 |pmid=31985968}}</ref> that provides [[energy]] to drive and support many processes in living [[cell (biology)|cells]], such as [[muscle contraction]], [[nerve impulse]] propagation, and [[chemical synthesis]]. Found in all known forms of [[life]], it is often referred to as the "molecular unit of [[currency]]" for intracellular [[energy transfer]].<ref>{{cite journal |last=Knowles |first=J.&nbsp;R. |title=Enzyme-catalyzed phosphoryl transfer reactions |journal=Annu. Rev. Biochem. |volume=49 |pages=877–919 |year=1980 |pmid=6250450 | doi=10.1146/annurev.bi.49.070180.004305}}</ref>

When consumed in a [[Metabolism|metabolic]] process, ATP converts either to [[adenosine diphosphate]] (ADP) or to [[adenosine monophosphate]] (AMP). Other processes regenerate ATP. It is also a [[Precursor (chemistry)|precursor]] to [[DNA]] and [[RNA]], and is used as a [[coenzyme]]. An average adult human processes around 50 kilograms (about 100 [[mole (unit)|mole]]s) daily.<ref>"An average individual with a daily diet of 8000 kJ and a 30% efficiency of turning foodstuffs into chemical energy will synthesize (and hydrolyze) about 50 kg of ATP during 1 day." {{cite book |doi=10.1002/9780470048672.wecb648 |chapter=ATP Synthesis, Chemistry of |title=Wiley Encyclopedia of Chemical Biology |date=2008 |last1=Wilkens |first1=Stephan |isbn=9780471754770 }}</ref>

From the perspective of [[biochemistry]], ATP is classified as a [[nucleoside triphosphate]], which indicates that it consists of three components: a nitrogenous base ([[adenine]]), the sugar [[ribose]], and the [[Polyphosphate|triphosphate]].

==Structure==
ATP consists of an [[adenine]] attached by the #9-nitrogen atom to the 1′ [[carbon]] [[atom]] of a sugar ([[ribose]]), which in turn is attached at the 5' carbon atom of the sugar to a triphosphate group. In its many reactions related to metabolism, the adenine and sugar groups remain unchanged, but the triphosphate is converted to di- and monophosphate, giving respectively the derivatives [[adenosine diphosphate|ADP]] and [[adenosine monophosphate|AMP]]. The three phosphoryl groups are labeled as alpha (α), beta (β), and, for the terminal phosphate, gamma (γ).<ref>{{Citation |last1=Dunn |first1=Jacob |title=Physiology, Adenosine Triphosphate |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK553175/ |work=StatPearls |access-date=2023-09-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31985968 |last2=Grider |first2=Michael H.}}</ref>

In neutral solution, ionized ATP exists mostly as ATP<sup>4−</sup>, with a small proportion of ATP<sup>3−</sup>.<ref name=Storer>{{cite journal |last1=Storer |first1=A.|author-link2=Athel Cornish-Bowden |last2=Cornish-Bowden |first2=A. | title = Concentration of MgATP<sup>2−</sup> and other ions in solution. Calculation of the true concentrations of species present in mixtures of associating ions | pmc=1164030 | journal = Biochem. J. | volume = 159 | issue = 1 | pages = 1–5 | year = 1976 | pmid = 11772 | doi=10.1042/bj1590001}}</ref>

===Metal cation binding===
Polyanionic and featuring a potentially [[chelation|chelating]] polyphosphate group, ATP binds metal cations with high affinity. The [[binding constant]] for {{chem|link=magnesium|Mg|2+}} is ({{gaps|9|554}}).<ref>{{cite journal |last1=Wilson |first1=J. |last2=Chin |first2=A. | title = Chelation of divalent cations by ATP, studied by titration calorimetry | journal = Anal. Biochem. | volume = 193 | issue = 1 | pages = 16–19 | year = 1991 | pmid = 1645933| doi=10.1016/0003-2697(91)90036-S}}</ref>  The binding of a [[divalent]] [[cation]], almost always [[magnesium]], strongly affects the interaction of ATP with various proteins. Due to the strength of the ATP-Mg<sup>2+</sup> interaction, ATP exists in the cell mostly as a complex with {{chem|Mg|2+}} bonded to the phosphate oxygen centers.<ref name=Storer/><ref>{{cite journal |last1=Garfinkel |first1=L. |last2=Altschuld |first2=R. |last3=Garfinkel |first3=D. | title = Magnesium in cardiac energy metabolism | journal = J. Mol. Cell. Cardiol. | volume = 18 | issue = 10 | pages = 1003–1013 | year = 1986 | pmid = 3537318 | doi = 10.1016/S0022-2828(86)80289-9 }}</ref>

A second magnesium ion is critical for ATP binding in the kinase domain.<ref name="Saylor">{{cite journal |last1=Saylor |first1=P. |last2=Wang |first2=C. |last3=Hirai |first3=T. |last4=Adams |first4=J. | title = A second magnesium ion is critical for ATP binding in the kinase domain of the oncoprotein v-Fps | journal = Biochemistry | volume = 37 | issue = 36 | pages = 12624–12630 | year = 1998 | pmid = 9730835 | doi = 10.1021/bi9812672 }}</ref> The presence of Mg<sup>2+</sup> regulates kinase activity.<ref name=Lin>{{cite journal |last1=Lin |first1=X. |last2=Ayrapetov |first2=M |last3=Sun |first3=G. | title = Characterization of the interactions between the active site of a protein tyrosine kinase and a divalent metal activator |pmc=1316873 | doi = 10.1186/1471-2091-6-25 |doi-access=free | journal = BMC Biochem. | volume = 6 | pages = 25 | year = 2005| pmid = 16305747}}</ref>   It is interesting from an RNA world perspective that ATP can carry a Mg ion which catalyzes RNA polymerization.{{cn|date=December 2023}}

==Chemical properties==
Salts of ATP can be isolated as colorless solids.<ref>{{Merck13th}}</ref>
[[File:ATP-ADP.svg|thumb|upright=1.5|The cycles of synthesis and degradation of ATP; 2 and 1 represent input and output of energy, respectively.]]

ATP is stable in aqueous solutions between [[pH]]&nbsp;6.8 and 7.4 (in the absence of catalysts).  At more extreme pH levels, it rapidly [[hydrolyses]] to ADP and phosphate. Living cells maintain the ratio of ATP to ADP at a point ten orders of magnitude from equilibrium, with ATP concentrations fivefold higher than the concentration of ADP.<ref name=Nicholls>{{cite book |last1=Ferguson |first1=S.&nbsp;J. |last2=Nicholls |first2=David |last3=Ferguson |first3=Stuart |title=Bioenergetics 3 |publisher=Academic |location=San Diego, CA |year=2002 |isbn=978-0-12-518121-1 |edition=3rd}}</ref><ref name="Stryer p376">{{cite book |first1=J.&nbsp;M. |last1=Berg |first2=J.&nbsp; L. |last2=Tymoczko |first3=L. |last3=Stryer | title = Biochemistry |url=https://archive.org/details/biochemistry200100jere |url-access=registration | publisher = W.&nbsp;H. Freeman | year = 2003 | location = New York, NY | page = [https://archive.org/details/biochemistry200100jere/page/376 376] |isbn = 978-0-7167-4684-3}}</ref> In the context of biochemical reactions, the P-O-P bonds are frequently referred to as [[high-energy phosphate|''high-energy bonds'']].<ref>{{cite journal |last1=Chance|first1= B. |last2=Lees|first2= H. |last3=Postgate|first3= J.&nbsp;G. | title = The Meaning of "Reversed Electron Flow" and "High Energy Electron" in Biochemistry|doi=10.1038/238330a0|journal = Nature | volume = 238 | pages = 330–331 | year = 1972 | pmid = 4561837 | issue = 5363 |bibcode= 1972Natur.238..330C |s2cid= 4298762 }}</ref>

==Reactive aspects==
The hydrolysis of ATP into ADP and inorganic phosphate

:ATP{{sup|4-}}(aq) + {{chem2|H2O}}(l) = ADP{{sup|3-}}(aq) + HPO{{sup|2-}}(aq) + H{{sup|+}}(aq)

releases {{convert|20.5|kJ/mol}} of [[enthalpy]]. This may differ under physiological conditions if the reactant and products are not exactly in these ionization states.<ref>{{cite journal |last1=Gajewski |first1=E. |last2=Steckler |first2=D. |last3=Goldberg |first3=R. |title=Thermodynamics of the hydrolysis of adenosine 5′-triphosphate to adenosine 5′-diphosphate |journal=J. Biol. Chem. |volume=261 |issue=27 |pages=12733–12737 |year=1986 |doi=10.1016/S0021-9258(18)67153-4 |pmid=3528161 |doi-access=free }}</ref> The values of the free energy released by cleaving either a phosphate (P<sub>i</sub>) or a pyrophosphate (PP<sub>i</sub>) unit from ATP at [[standard state]] concentrations of 1&nbsp;mol/L at pH&nbsp;7 are:<ref>{{cite book |title=Biochemistry |last1=Berg |first1=Jeremy M. |last2=Tymoczko|first2= John L.|last3= Stryer|first3= Lubert |year=2007 |edition=6th |publisher=W.&nbsp;H. Freeman |location=New York, NY |isbn=978-0-7167-8724-2 |page=413}}</ref>

:ATP + {{chem|H|2|O}} → ADP + P<sub>i</sub> {{pad|1.5em}} Δ''G''°' = −30.5&nbsp;kJ/mol (−7.3&nbsp;kcal/mol)
:ATP + {{chem|H|2|O}} → AMP + PP<sub>i</sub> {{pad|1em}}Δ''G''°' = −45.6&nbsp;kJ/mol (−10.9&nbsp;kcal/mol)
These abbreviated equations at a pH near 7 can be written more explicitly (R = [[adenosine|adenosyl]]):
:[RO-P(O)<sub>2</sub>-O-P(O)<sub>2</sub>-O-PO<sub>3</sub>]<sup>4−</sup> + {{chem|H|2|O}} → [RO-P(O)<sub>2</sub>-O-PO<sub>3</sub>]<sup>3−</sup> + [HPO<sub>4</sub>]<sup>2−</sup> +  H<sup>+</sup>
:[RO-P(O)<sub>2</sub>-O-P(O)<sub>2</sub>-O-PO<sub>3</sub>]<sup>4−</sup> + {{chem|H|2|O}} → [RO-PO<sub>3</sub>]<sup>2−</sup> + [HO<sub>3</sub>P-O-PO<sub>3</sub>]<sup>3−</sup> +  H<sup>+</sup>

At cytoplasmic conditions, where the ADP/ATP ratio is 10 orders of magnitude from equilibrium, the Δ''G'' is around −57&nbsp;kJ/mol.<ref name=Nicholls/>

Along with pH, the free energy change of ATP hydrolysis is also associated with Mg<sup>2+</sup> concentration, from ΔG°' = −35.7&nbsp;kJ/mol at a Mg<sup>2+</sup> concentration of zero, to ΔG°' = −31&nbsp;kJ/mol at [Mg<sup>2+</sup>] = 5&nbsp;mM. Higher concentrations of Mg<sup>2+</sup> decrease free energy released in the reaction due to binding of Mg<sup>2+</sup> ions to negatively charged oxygen atoms of ATP at pH&nbsp;7.<ref>{{cite book |last1=Garrett |first1=Reginald H. |last2=Grisham |first2=Charles M. |edition=6th |date=2016 |title=Biochemistry |publisher=Cengage Learning |page=68 |isbn=978-1305577206}}</ref>

[[File:MgATP2-small.gif|thumb|This image shows a 360-degree rotation of a single, gas-phase [[magnesium]]-ATP chelate with a charge of −2. The anion was optimized at the UB3LYP/6-311++G(d,p) theoretical level and the atomic connectivity modified by the human optimizer to reflect the probable electronic structure.]]

==Production from AMP and ADP==
===Production, aerobic conditions===
A typical intracellular [[concentration]] of ATP may be 1–10&nbsp;μmol per gram of tissue in a variety of eukaryotes.<ref>{{cite journal| last1 = Beis |first1=I. |last2= Newsholme |first2=E.&nbsp;A. | date = October 1, 1975 | title= The contents of adenine nucleotides, phosphagens and some glycolytic intermediates in resting muscles from vertebrates and invertebrates | journal= Biochem. J. | volume=152 | pages= 23–32 | pmid=1212224 |pmc=1172435| issue = 1 | doi=10.1042/bj1520023}}
</ref> The dephosphorylation of ATP and rephosphorylation of ADP and AMP occur repeatedly in the course of aerobic metabolism.<ref name="brit">{{cite web |title=Adenosine triphosphate |url=https://www.britannica.com/science/adenosine-triphosphate |publisher=Britannica |access-date=1 December 2023 |date=11 November 2023}}</ref>

ATP can be produced by a number of distinct cellular processes; the three main pathways in [[eukaryote]]s are (1) [[glycolysis]], (2) the [[citric acid cycle]]/[[oxidative phosphorylation]], and (3) [[beta-oxidation]]. The overall process of oxidizing [[glucose]] to [[carbon dioxide]], the combination of pathways 1 and 2, known as [[cellular respiration]], produces about 30 equivalents of ATP from each molecule of glucose.<ref name=Rich>{{cite journal |last=Rich |first=P.&nbsp;R. |title=The molecular machinery of Keilin's respiratory chain |journal=Biochem. Soc. Trans. |volume=31 |issue=6 |pages=1095–1105 |year=2003 |pmid=14641005 |doi=10.1042/BST0311095}}</ref>

ATP production by a non-[[photosynthetic]] aerobic eukaryote occurs mainly in the [[mitochondria]], which comprise nearly 25% of the volume of a typical cell.<ref name="Lodish">{{cite book |last1=Lodish |first1=H. |last2=Berk |first2=A. |last3=Matsudaira |first3=P. |last4=Kaiser |first4=C.&nbsp;A. |last5=Krieger |first5=M. |last6=Scott |first6=M.&nbsp;P. |last7=Zipursky |first7=S.&nbsp;L. |last8=Darnell |first8=J. |title=Molecular Cell Biology |edition=5th |publisher=W.&nbsp;H. Freeman |location=New York, NY |isbn=978-0-7167-4366-8 |year=2004 |url-access=registration |url=https://archive.org/details/molecularcellbio00harv }}</ref>

====Glycolysis====
{{Main|Glycolysis}}

In glycolysis, glucose and glycerol are metabolized to [[pyruvate]]. Glycolysis generates two equivalents of ATP through [[substrate-level phosphorylation|substrate phosphorylation]] catalyzed by two enzymes,  [[phosphoglycerate kinase]] (PGK) and [[pyruvate kinase]]. Two equivalents of [[nicotinamide adenine dinucleotide]] (NADH) are also produced, which can be oxidized via the [[electron transport chain]] and result in the generation of additional ATP by [[ATP synthase]]. The pyruvate generated as an end-product of glycolysis is a substrate for the [[citric acid cycle|Krebs Cycle]].<ref name=Voet>{{cite book |last1=Voet |first1=D. |last2=Voet |first2=J.&nbsp;G. | year=2004 | title=Biochemistry |volume=1 |edition=3rd | publisher= Wiley |location=Hoboken, NJ | isbn = 978-0-471-19350-0}}</ref>

Glycolysis is viewed as consisting of two phases with five steps each. In phase 1, "the preparatory phase", glucose is converted to 2 d-glyceraldehyde-3-phosphate (g3p). One ATP is invested in Step 1, and another ATP is invested in Step 3. Steps 1 and 3 of glycolysis are referred to as "Priming Steps". In Phase 2, two equivalents of g3p are converted to two pyruvates. In Step 7, two ATP are produced. Also, in Step 10, two further equivalents of ATP are produced. In Steps 7 and 10, ATP is generated from ADP. A net of two ATPs is formed in the glycolysis cycle. The glycolysis pathway is later associated with the Citric Acid Cycle which produces additional equivalents of ATP.{{citation needed|date=April 2023}}

=====Regulation=====
In glycolysis, [[hexokinase]] is directly inhibited by its product, glucose-6-phosphate, and [[pyruvate kinase]] is inhibited by ATP itself. The main control point for the glycolytic pathway is [[phosphofructokinase]] (PFK), which is allosterically inhibited by high concentrations of ATP and activated by high concentrations of AMP. The inhibition of PFK by ATP is unusual since ATP is also a substrate in the reaction catalyzed by PFK; the active form of the enzyme is a [[tetramer protein|tetramer]] that exists in two conformations, only one of which binds the second substrate fructose-6-phosphate (F6P). The protein has two [[binding site]]s for ATP&nbsp;– the [[active site]] is accessible in either protein conformation, but ATP binding to the inhibitor site stabilizes the conformation that binds F6P poorly.<ref name="Voet" /> A number of other small molecules can compensate for the ATP-induced shift in equilibrium conformation and reactivate PFK, including [[cyclic AMP]], [[ammonium]] ions, inorganic phosphate, and fructose-1,6- and -2,6-biphosphate.<ref name="Voet" /> {{confusing|date=October 2024}}

====Citric acid cycle====
{{Main|Citric acid cycle|Oxidative phosphorylation}}

In the [[mitochondrion]], pyruvate is oxidized by the [[pyruvate dehydrogenase complex]] to the [[acetyl]] group, which is fully oxidized to carbon dioxide by the [[citric acid cycle]] (also known as the [[Hans Krebs (biochemist)|Krebs]] cycle). Every "turn" of the citric acid cycle produces two molecules of carbon dioxide, one equivalent of ATP [[guanosine triphosphate]] (GTP) through [[substrate-level phosphorylation]] catalyzed by [[succinyl-CoA synthetase]], as succinyl-CoA is converted to succinate, three equivalents of NADH, and one equivalent of [[Flavin group|FADH<sub>2</sub>]]. NADH and FADH<sub>2</sub> are recycled (to NAD<sup>+</sup> and [[Flavin adenine dinucleotide|FAD]], respectively) by [[oxidative phosphorylation]], generating additional ATP. The oxidation of NADH results in the synthesis of 2–3 equivalents of ATP, and the oxidation of one FADH<sub>2</sub> yields between 1–2 equivalents of ATP.<ref name="Rich" /> The majority of cellular ATP is generated by this process. Although the citric acid cycle itself does not involve molecular [[oxygen]], it is an obligately [[aerobic glycolysis|aerobic]] process because O<sub>2</sub> is used to recycle the NADH and FADH<sub>2</sub>. In the absence of oxygen, the citric acid cycle ceases.<ref name="Lodish" />

The generation of ATP by the mitochondrion from cytosolic NADH relies on the [[malate-aspartate shuttle]] (and to a lesser extent, the [[glycerol-phosphate shuttle]]) because the inner mitochondrial membrane is impermeable to NADH and NAD<sup>+</sup>. Instead of transferring the generated NADH, a [[malate dehydrogenase]] enzyme converts [[oxaloacetate]] to [[malate]], which is translocated to the mitochondrial matrix. Another malate dehydrogenase-catalyzed reaction occurs in the opposite direction, producing oxaloacetate and NADH from the newly transported malate and the mitochondrion's interior store of NAD<sup>+</sup>. A [[transaminase]] converts the oxaloacetate to [[aspartate]] for transport back across the membrane and into the intermembrane space.<ref name="Lodish" /><!--will put the antiporter/full cycle in the shuttle article-->

In oxidative phosphorylation, the passage of electrons from NADH and FADH<sub>2</sub> through the electron transport chain releases the energy to pump [[proton]]s out of the mitochondrial matrix and into the intermembrane space. This pumping generates a [[proton motive force]] that is the net effect of a pH gradient and an [[electric potential]] gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient&nbsp;– that is, from the intermembrane space to the matrix&nbsp;– yields ATP by ATP synthase.<ref>{{cite journal |last1=Abrahams |first1=J. |last2=Leslie |first2=A. |last3=Lutter |first3=R. |last4=Walker |first4=J. | title = Structure at 2.8&nbsp;Å resolution of F1-ATPase from bovine heart mitochondria | journal = Nature | volume = 370 | issue = 6491 | pages = 621–628 | year = 1994 |pmid=8065448 | doi = 10.1038/370621a0 |bibcode=1994Natur.370..621A |s2cid=4275221 }}</ref> Three ATP are produced per turn.

Although oxygen consumption appears fundamental for the maintenance of the proton motive force, in the event of oxygen shortage ([[Hypoxia (medical)|hypoxia]]), intracellular acidosis (mediated by enhanced glycolytic rates and [[ATP hydrolysis]]), contributes to mitochondrial membrane potential and directly drives ATP synthesis.<ref>{{cite journal | pmid = 30713504 | volume=9, 1914 | title=Acidosis Maintains the Function of Brain Mitochondria in Hypoxia-Tolerant Triplefin Fish: A Strategy to Survive Acute Hypoxic Exposure? | pmc=6346031 | date=January 2019 | journal=Front Physiol | doi=10.3389/fphys.2018.01941 | last1 = Devaux | first1 = JBL | last2 = Hedges | first2 = CP | last3 = Hickey | first3 = AJR| page=1941 | doi-access=free }}</ref>

Most of the ATP synthesized in the mitochondria will be used for cellular processes in the cytosol; thus it must be exported from its site of synthesis in the mitochondrial matrix. ATP outward movement is favored by the membrane's electrochemical potential because the cytosol has a relatively positive charge compared to the relatively negative matrix. For every ATP transported out, it costs 1 H<sup>+</sup>. Producing one ATP costs about 3  H<sup>+</sup>. Therefore, making and exporting one ATP requires  4H<sup>+.</sup> The inner membrane contains an [[antiporter]], the ADP/ATP translocase, which is an [[integral membrane protein]] used to exchange newly synthesized ATP in the matrix for ADP in the intermembrane space.<ref name="Brandolin">{{cite journal |last1=Dahout-Gonzalez |first1=C. |last2=Nury |first2=H. |last3=Trézéguet |first3=V. |last4=Lauquin |first4=G. |last5=Pebay-Peyroula |first5=E. |last6=Brandolin |first6=G. | title = Molecular, functional, and pathological aspects of the mitochondrial ADP/ATP carrier | journal = Physiology | volume = 21 | pages = 242–249 | year = 2006| pmid = 16868313 | doi=10.1152/physiol.00005.2006 | issue = 4 }}</ref>

=====Regulation=====
The citric acid cycle is regulated mainly by the availability of key substrates, particularly the ratio of NAD<sup>+</sup> to NADH and the concentrations of [[calcium]], inorganic phosphate, ATP, ADP, and AMP. [[Citrate]]&nbsp;– the ion that gives its name to the cycle&nbsp;– is a feedback inhibitor of [[citrate synthase]] and also inhibits PFK, providing a direct link between the regulation of the citric acid cycle and glycolysis.<ref name="Voet" /> {{confusing|date=October 2024}}

====Beta oxidation====
{{Main|Beta-oxidation}}
In the presence of air and various cofactors and enzymes, fatty acids are converted to [[acetyl-CoA]]. The pathway is called [[beta-oxidation]]. Each cycle of beta-oxidation shortens the fatty acid chain by two carbon atoms and produces one equivalent each of acetyl-CoA, NADH, and FADH<sub>2</sub>. The acetyl-CoA is metabolized by the citric acid cycle to generate ATP, while the NADH and FADH<sub>2</sub> are used  by oxidative phosphorylation to generate ATP.  Dozens of ATP equivalents are generated by the beta-oxidation of a single long acyl chain.<ref>{{cite journal |last1=Ronnett |first1=G. |last2=Kim |first2=E. |last3=Landree |first3=L. |last4=Tu |first4=Y. | title = Fatty acid metabolism as a target for obesity treatment | journal = Physiol. Behav. | volume = 85 | issue = 1 | pages = 25–35 | year = 2005 | pmid = 15878185 | doi=10.1016/j.physbeh.2005.04.014 |s2cid=24865576 }}</ref>

=====Regulation=====
In oxidative phosphorylation, the key control point is the reaction catalyzed by [[cytochrome c oxidase]], which is regulated by the availability of its substrate&nbsp;– the reduced form of [[cytochrome c]]. The amount of reduced cytochrome c available is directly related to the amounts of other substrates:

:<math chem="">
\frac12 \ce{NADH} + \ce{cyt}\ \ce{c_{ox}} + \ce{ADP} + \ce{P_{i}} \rightleftharpoons
\frac12 \ce{NAD^+} + \ce{cyt}\ \ce{c_{red}} + \ce{ATP}
</math>

which directly implies this equation:

:<math>
\frac{[\mathrm{cyt~c_{red}}]}{[\mathrm{cyt~c_{ox}}]} = \left(\frac{[\mathrm{NADH}]}{[\mathrm{NAD}]^{+}}\right)^{\frac{1}{2}}\left(\frac{[\mathrm{ADP}] [\mathrm{P_i}]}{[\mathrm{ATP}]}\right)K_\mathrm{eq}
</math>

Thus, a high ratio of [NADH] to [NAD<sup>+</sup>] or a high ratio of [ADP] [P<sub>i</sub>] to [ATP] imply a high amount of reduced cytochrome c and a high level of cytochrome c oxidase activity.<ref name="Voet" /> An additional level of regulation is introduced by the transport rates of ATP and NADH between the mitochondrial matrix and the cytoplasm.<ref name="Brandolin" />

====Ketosis====
{{Main|Ketone bodies}}

Ketone bodies can be used as fuels, yielding 22 ATP and 2 [[Guanosine triphosphate|GTP]] molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the [[liver]] to other tissues, where [[acetoacetate]] and [[beta-Hydroxybutyric acid|''beta''-hydroxybutyrate]] can be reconverted to acetyl-CoA to produce reducing equivalents (NADH and FADH<sub>2</sub>), via the citric acid cycle. Ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme β-ketoacyl-CoA transferase, also called [[thiolase]]. [[Acetoacetate]] in low concentrations is taken up by the liver and undergoes detoxification through the methylglyoxal pathway which ends with lactate. Acetoacetate in high concentrations is absorbed by cells other than those in the liver and enters a different pathway via [[1,2-propanediol]].  Though the pathway follows a different series of steps requiring ATP, 1,2-propanediol can be turned into pyruvate.<ref name="Environmental Protection Agency; TOXICOLOGICAL REVIEW OF ACETONE (CAS No. 67-64-1)">{{Cite web| url=http://www.epa.gov/iris/toxreviews/0128tr.pdf| title=Integrated Risk Information System| date=2013-03-15| access-date=2019-02-01| archive-url=https://web.archive.org/web/20150924074331/http://www.epa.gov/iris/toxreviews/0128tr.pdf| archive-date=2015-09-24| url-status=live}}</ref>

===Production, anaerobic conditions===
[[fermentation (biochemistry)|Fermentation]] is the metabolism of organic compounds in the absence of air. It involves [[substrate-level phosphorylation]] in the absence of a respiratory [[electron transport chain]]. The equation for the reaction of glucose to form [[lactic acid]] is:
: {{chem|C|6|H|12|O|6}} + 2&nbsp;ADP + 2&nbsp;P<sub>i</sub> → 2&nbsp;{{chem|CH|3|CH(OH)COOH}} + 2&nbsp;ATP + 2&nbsp;{{chem|H|2|O}}

[[Anaerobic respiration]] is respiration in the absence of {{chem|link=oxygen|O|2}}. Prokaryotes can utilize a variety of electron acceptors. These include [[nitrate]], [[sulfate]], and carbon dioxide.

====ATP replenishment by nucleoside diphosphate kinases====
ATP can also be synthesized through several so-called "replenishment" reactions catalyzed by the enzyme families of [[nucleoside diphosphate kinase]]s (NDKs), which use other nucleoside triphosphates as a high-energy phosphate donor, and the [[ATP:guanido phosphotransferase family|ATP:guanido-phosphotransferase]] family.{{citation needed|date=April 2023}}

===ATP production during photosynthesis===
In plants, ATP is synthesized in the [[thylakoid membrane]] of the [[chloroplast]]. The process is called [[photophosphorylation]]. The "machinery" is similar to that in mitochondria except that light energy is used to pump protons across a membrane to produce a proton-motive force. ATP synthase then ensues exactly as in oxidative phosphorylation.<ref>{{cite journal | last = Allen | first = J. | title = Photosynthesis of ATP-electrons, proton pumps, rotors, and poise | journal = Cell | volume = 110 | issue = 3 | pages = 273–276 | year = 2002 | pmid = 12176312 | doi = 10.1016/S0092-8674(02)00870-X | s2cid = 1754660 | doi-access = free }}</ref> Some of the ATP produced in the chloroplasts is consumed in the [[Calvin cycle]], which produces [[triose]] sugars.

===ATP recycling===
The total quantity of ATP in the human body is about 0.1&nbsp;[[Molar concentration|mol/L]].<ref name="Fuhrman-1061">{{cite book |last1=Fuhrman |first1=Bradley P. |last2=Zimmerman |first2=Jerry J. |title=Pediatric Critical Care |date=2011 |publisher=Elsevier |isbn=978-0-323-07307-3 |pages=1061 |url=https://www.sciencedirect.com/science/article/pii/B9780323073073100746#s0025 |access-date=16 May 2020}}</ref> The majority of ATP is recycled from ADP by the aforementioned processes. Thus, at any given time, the total amount of ATP + ADP remains fairly constant.

The energy used by human cells in an adult requires the hydrolysis of 100 to 150&nbsp;mol/L of ATP daily, which means a human will typically use their body weight worth of ATP over the course of the day.<ref name="Fuhrman">{{cite book |last1=Fuhrman |first1=Bradley P. |last2=Zimmerman |first2=Jerry J. |title=Pediatric Critical Care |date=2011 |publisher=Elsevier |isbn=978-0-323-07307-3 |pages=1058–1072 |url=https://www.sciencedirect.com/science/article/pii/B9780323073073100746#s0025 |access-date=16 May 2020}}</ref> Each equivalent of ATP is recycled 1000–1500 times during a single day ({{nowrap|150 / 0.1 {{=}} 1500}}),<ref name="Fuhrman-1061" /> at approximately 9×10<sup>20</sup> molecules/s.<ref name="Fuhrman-1061" />

[[Image:Rossmann-fold-1g5q.png|thumb|An example of the Rossmann fold, a [[structural domain]] of a [[decarboxylase]] enzyme from the bacterium ''[[Staphylococcus epidermidis]]'' ({{PDB|1G5Q}}) with a bound [[flavin mononucleotide]] cofactor]]

==Biochemical functions==
===Intracellular signaling===
ATP is involved in [[signal transduction]] by serving as substrate for kinases, enzymes that transfer phosphate groups.  Kinases are the most common ATP-binding proteins.  They share a small number of common folds.<ref name=Scheeff>{{cite journal |last1=Scheeff |first1=E. |last2=Bourne |first2=P. | title = Structural evolution of the protein kinase-like superfamily |pmc=1261164 | doi = 10.1371/journal.pcbi.0010049 |doi-access=free | journal = PLOS Comput. Biol. | volume = 1 | issue = 5 | pages = e49 | year = 2005 | pmid = 16244704|bibcode=2005PLSCB...1...49S }}</ref>  [[Phosphorylation]] of a protein by a kinase can activate a cascade such as the [[mitogen-activated protein kinase]] cascade.<ref>{{cite journal |last1=Mishra |first1=N. |last2=Tuteja |first2=R. |last3=Tuteja |first3=N. | title = Signaling through MAP kinase networks in plants | journal = Arch. Biochem. Biophys. | volume = 452 | issue = 1 | pages = 55–68 | year = 2006 | pmid = 16806044 | doi = 10.1016/j.abb.2006.05.001 }}</ref>

ATP is also a substrate of [[adenylate cyclase]], most commonly in [[G protein–coupled receptor|G protein-coupled receptor]] signal transduction pathways and is transformed to [[second messenger]], cyclic AMP, which is involved in triggering calcium signals by the release of calcium from intracellular stores.<ref>{{cite journal |last1=Kamenetsky |first1=M. |last2=Middelhaufe |first2=S. |last3=Bank |first3=E. |last4=Levin |first4=L. |last5=Buck |first5=J. |last6=Steegborn |first6=C. | title = Molecular details of cAMP generation in mammalian cells: a tale of two systems | journal = J. Mol. Biol. | volume = 362 | issue = 4 | pages = 623–639 | year = 2006 | pmid = 16934836 | doi = 10.1016/j.jmb.2006.07.045 | pmc = 3662476}}</ref> This form of signal transduction is particularly important in brain function, although it is involved in the regulation of a multitude of other cellular processes.<ref>{{cite journal |last1=Hanoune |first1=J. |last2=Defer |first2=N. | title = Regulation and role of adenylyl cyclase isoforms | journal = Annu. Rev. Pharmacol. Toxicol. | volume = 41 | pages = 145–174 | year = 2001|issue=1 | pmid = 11264454 | doi = 10.1146/annurev.pharmtox.41.1.145 }}</ref>

===DNA and RNA synthesis===
ATP is one of four monomers required in the synthesis of [[RNA]]. The process is promoted by [[RNA polymerase]]s.<ref>{{cite journal |last1=Joyce |first1=C.&nbsp;M. |last2=Steitz |first2=T.&nbsp;A. |title=Polymerase structures and function: variations on a theme? |journal=J. Bacteriol. |volume=177 |issue=22 |pages=6321–6329 |year=1995 |pmid=7592405 |pmc=177480 |doi=10.1128/jb.177.22.6321-6329.1995}}</ref> A similar process occurs in the formation of DNA, except that ATP is first converted to the [[deoxyribonucleotide]] dATP.  Like many condensation reactions in nature, [[DNA replication]] and [[DNA transcription]] also consume ATP.

===Amino acid activation in protein synthesis===
{{main|Amino acid activation}}
[[Aminoacyl-tRNA synthetase]] enzymes consume ATP in the attachment tRNA to amino acids, forming aminoacyl-tRNA complexes. Aminoacyl transferase binds AMP-amino acid to tRNA. The coupling reaction proceeds in two steps:

# aa + ATP ⟶ aa-AMP + [[pyrophosphate|PP<sub>i</sub>]]
# aa-AMP + tRNA ⟶ aa-tRNA + AMP

The amino acid is coupled to the penultimate nucleotide at the 3′-end of the tRNA (the A in the sequence CCA) via an ester bond (roll over in illustration).

===ATP binding cassette transporter===
Transporting chemicals out of a cell against a gradient is often associated with ATP hydrolysis.  Transport is mediated by [[ATP binding cassette transporter]]s.  The human genome encodes 48 ABC transporters, that are used for exporting drugs, lipids, and other compounds.<ref>{{cite journal|title=Mammalian ABC transporters in health and disease|author1=Borst, P. |author2=Elferink, R. Oude|journal=Annual Review of Biochemistry|year=2002|volume=71|pages=537–592|doi=10.1146/annurev.biochem.71.102301.093055|pmid=12045106|s2cid=34707074 |url=https://pure.uva.nl/ws/files/3499814/42885_202387y.pdf|access-date=2018-04-20|archive-url=https://web.archive.org/web/20180421032744/https://pure.uva.nl/ws/files/3499814/42885_202387y.pdf|archive-date=2018-04-21|url-status=live}}</ref>

===Extracellular signalling and neurotransmission===
Cells secrete ATP to communicate with other cells in a process called [[purinergic signalling]]. ATP serves as a [[neurotransmitter]] in many parts of the nervous system, modulates ciliary beating, affects vascular oxygen supply etc.  ATP is either secreted directly across the cell membrane through channel proteins<ref name="RomanovLasher2018">{{cite journal|last1=Romanov|first1=Roman A.|last2=Lasher|first2=Robert S.|last3=High|first3=Brigit|last4=Savidge|first4=Logan E.|last5=Lawson|first5=Adam|last6=Rogachevskaja|first6=Olga A.|last7=Zhao|first7=Haitian|last8=Rogachevsky|first8=Vadim V.|last9=Bystrova|first9=Marina F.|last10=Churbanov|first10=Gleb D.|last11=Adameyko|first11=Igor|last12=Harkany|first12=Tibor|last13=Yang|first13=Ruibiao|last14=Kidd|first14=Grahame J.|last15=Marambaud|first15=Philippe|last16=Kinnamon|first16=John C.|last17=Kolesnikov|first17=Stanislav S.|last18=Finger|first18=Thomas E.|title=Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex|journal=Science Signaling|volume=11|issue=529|year=2018|pages=eaao1815|issn=1945-0877|doi=10.1126/scisignal.aao1815|pmid=29739879|pmc=5966022}}</ref><ref name="Dahl2015">{{cite journal|last1=Dahl|first1=Gerhard|title=ATP release through pannexon channels|journal=Philosophical Transactions of the Royal Society B: Biological Sciences|volume=370|issue=1672|year=2015|pages=20140191|issn=0962-8436|doi=10.1098/rstb.2014.0191|pmid=26009770|pmc=4455760}}</ref> or is pumped into vesicles<ref name="LarssonSawada2012">{{cite journal|last1=Larsson|first1=Max|last2=Sawada|first2=Keisuke|last3=Morland|first3=Cecilie|last4=Hiasa|first4=Miki|last5=Ormel|first5=Lasse|last6=Moriyama|first6=Yoshinori|last7=Gundersen|first7=Vidar|title=Functional and Anatomical Identification of a Vesicular Transporter Mediating Neuronal ATP Release|journal=Cerebral Cortex|volume=22|issue=5|year=2012|pages=1203–1214|issn=1460-2199|doi=10.1093/cercor/bhr203|pmid=21810784|doi-access=free}}</ref> which then [[exocytosis|fuse]] with the membrane. Cells detect ATP using the [[purinergic receptor]] proteins [[P2X purinoreceptor|P2X]] and [[P2Y receptor|P2Y]].<ref>{{Cite journal |last1=Puchałowicz |first1=Kamila |last2=Tarnowski |first2=Maciej |last3=Baranowska-Bosiacka |first3=Irena |last4=Chlubek |first4=Dariusz |last5=Dziedziejko |first5=Violetta |date=2014-12-18 |title=P2X and P2Y Receptors—Role in the Pathophysiology of the Nervous System |journal=International Journal of Molecular Sciences |volume=15 |issue=12 |pages=23672–23704 |doi=10.3390/ijms151223672 |doi-access=free |issn=1422-0067 |pmc=4284787 |pmid=25530618}}</ref> ATP has been shown to be a critically important signalling molecule for [[microglia]] - [[neuron]] interactions in the adult brain,<ref> {{cite journal | url=https://www.science.org/doi/10.1126/science.aax6752 | doi=10.1126/science.aax6752   | title=Microglia monitor and protect neuronal function through specialized somatic purinergic junctions | date=2020 | last1=Csaba | first1=Cserep | last2=Balazs | first2=Pósfai | journal=Science | volume=367 | issue=6477 | pages=528–537 | pmid= 31831638 | bibcode=2020Sci...367..528C }} </ref> as well as during brain development.<ref> {{cite journal | doi=10.1016/j.celrep.2022.111369    | title=Microglial control of neuronal development via somatic purinergic junctions | date=2022 | last1=Csaba | first1=Cserep | last2=Anett | first2=Schwarcz D | journal=Cell Reports | volume=40 | issue=12 | pmid=36130488  | pmc=9513806 }} </ref> Furthermore, tissue-injury induced ATP-signalling is a major factor in rapid microglial phenotype changes.<ref> {{cite journal | doi= 10.1038/s41467-024-49773-1  | title=Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices | date=2024 | last1=Peter | first1=Berki | last2=Csaba | first2=Cserep | last3=Zsuzsanna | first3=Környei | journal=Nature Communications | volume= 15 | issue= 1 | page= 5402 | pmid= 38926390 | pmc=11208608 | bibcode= 2024NatCo..15.5402B }} </ref>

=== Muscle contraction ===
ATP fuels [[muscle contraction]]s.<ref>{{Cite journal |last1=Hultman |first1=E. |last2=Greenhaff |first2=P. L. |date=1991 |title=Skeletal muscle energy metabolism and fatigue during intense exercise in man |url=https://pubmed.ncbi.nlm.nih.gov/1842855/ |journal=Science Progress |volume=75 |issue=298 Pt 3-4 |pages=361–370 |issn=0036-8504 |pmid=1842855}}</ref> Muscle contractions are regulated by signaling pathways, although different [[muscle]] types being regulated by specific pathways and stimuli based on their particular function. However, in all muscle types, contraction is performed by the proteins [[actin]] and [[myosin]].<ref name=":0">{{Cite journal |last1=Kuo |first1=Ivana Y. |last2=Ehrlich |first2=Barbara E. |date=February 2015 |title=Signaling in Muscle Contraction |journal=Cold Spring Harbor Perspectives in Biology |language=en |volume=7 |issue=2 |pages=a006023 |doi=10.1101/cshperspect.a006023 |issn=1943-0264 |pmc=4315934 |pmid=25646377}}</ref>

ATP is initially bound to myosin. When [[ATPase]] hydrolyzes the bound ATP into [[Adenosine diphosphate|ADP]] and inorganic [[phosphate]], myosin is positioned in a way that it can bind to actin. Myosin bound by ADP and P<sub>i</sub> forms cross-bridges with actin and the subsequent release of ADP and P<sub>i</sub> releases energy as the power stroke. The power stroke causes actin filament to slide past the myosin filament, shortening the muscle and causing a contraction. Another ATP molecule can then bind to myosin, releasing it from actin and allowing this process to repeat.<ref name=":0" /><ref>{{Cite web |date=2018-07-16 |title=38.17: Muscle Contraction and Locomotion - ATP and Muscle Contraction |url=https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/38%3A_The_Musculoskeletal_System/38.17%3A_Muscle_Contraction_and_Locomotion_-_ATP_and_Muscle_Contraction |access-date=2024-05-01 |website=Biology LibreTexts |language=en}}</ref>

=== Protein solubility ===
ATP has recently been proposed to act as a biological [[hydrotrope]]<ref>{{Cite journal|last1=Hyman|first1=Anthony A.|last2=Krishnan|first2=Yamuna|last3=Alberti|first3=Simon|last4=Wang|first4=Jie|last5=Saha|first5=Shambaditya|last6=Malinovska|first6=Liliana|last7=Patel|first7=Avinash|date=2017-05-19|title=ATP as a biological hydrotrope|journal=Science|language=en|volume=356|issue=6339|pages=753–756|doi=10.1126/science.aaf6846|issn=0036-8075|pmid=28522535|bibcode=2017Sci...356..753P|s2cid=24622983}}</ref> and has been shown to affect proteome-wide solubility.<ref>{{Cite journal|last1=Savitski|first1=Mikhail M.|last2=Bantscheff|first2=Marcus|last3=Huber|first3=Wolfgang|last4=Dominic Helm|last5=Günthner|first5=Ina|last6=Werner|first6=Thilo|last7=Kurzawa|first7=Nils|last8=Sridharan|first8=Sindhuja|date=2019-03-11|title=Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP|journal=Nature Communications|language=en|volume=10|issue=1|pages=1155|doi=10.1038/s41467-019-09107-y|pmid=30858367|pmc=6411743|bibcode=2019NatCo..10.1155S|issn=2041-1723}}</ref>

== Abiogenic origins ==
Acetyl phosphate (AcP), a precursor to ATP, can readily be synthesized at modest yields from thioacetate in pH&nbsp;7 and 20&nbsp;°C and pH 8 and 50&nbsp;°C, although acetyl phosphate is less stable in warmer temperatures and alkaline conditions than in cooler and acidic to neutral conditions. It is unable to promote polymerization of ribonucleotides and amino acids and was only capable of phosphorylation of organic compounds. It was shown that it can promote aggregation and stabilization of AMP in the presence of Na<sup>+</sup>, aggregation of nucleotides could promote polymerization above 75&nbsp;°C in the absence of Na<sup>+</sup>. It is possible that polymerization promoted by AcP could occur at mineral surfaces.<ref>{{Cite journal |last1=Whicher |first1=Alexandra |last2=Camprubi |first2=Eloi |last3=Pinna |first3=Silvana |last4=Herschy |first4=Barry |last5=Lane |first5=Nick |date=2018-06-01 |title=Acetyl Phosphate as a Primordial Energy Currency at the Origin of Life |journal=Origins of Life and Evolution of Biospheres |language=en |volume=48 |issue=2 |pages=159–179 |doi=10.1007/s11084-018-9555-8 |issn=1573-0875 |pmc=6061221 |pmid=29502283|bibcode=2018OLEB...48..159W }}</ref> It was shown that ADP can only be phosphorylated to ATP by AcP and other nucleoside triphosphates were not phosphorylated by AcP. This might explain why all lifeforms use ATP to drive biochemical reactions.<ref>{{Cite web |title=Ancient chemistry may explain why living things use ATP as the universal energy currency: An early step in metabolic evolution set the stage for emergence of ATP as the universal energy carrier |url=https://www.sciencedaily.com/releases/2022/10/221004151228.htm |access-date=2023-08-27 |website=ScienceDaily |language=en}}</ref>

==ATP analogues==
Biochemistry laboratories often use ''[[in vitro]]'' studies to explore ATP-dependent molecular processes. ATP analogs are also used in [[X-ray crystallography]] to determine a [[protein structure]] in complex with ATP, often together with other substrates.{{citation needed|date=April 2023}}

[[Enzyme inhibitor]]s of ATP-dependent enzymes such as [[kinase]]s are needed to examine the [[binding site]]s and [[transition state]]s involved in ATP-dependent reactions.{{citation needed|date=April 2023}}

Most useful ATP analogs cannot be hydrolyzed as ATP would be; instead, they trap the enzyme in a structure closely related to the ATP-bound state. Adenosine 5′-(γ-thiotriphosphate) is an extremely common ATP analog in which one of the gamma-phosphate oxygens is replaced by a [[sulfur]] atom; this anion is hydrolyzed at a dramatically slower rate than ATP itself and functions as an inhibitor of ATP-dependent processes. In crystallographic studies, hydrolysis transition states are modeled by the bound [[vanadate]] ion.

Caution is warranted in interpreting the results of experiments using ATP analogs, since some enzymes can hydrolyze them at appreciable rates at high concentration.<ref name=Resetar>{{cite journal |last1=Resetar |first1=A.&nbsp;M. |last2=Chalovich |first2=J.&nbsp;M. | year=1995 | title= Adenosine 5′-(gamma-thiotriphosphate): an ATP analog that should be used with caution in muscle contraction studies | volume=34 | issue=49 | pages=16039–16045 | pmid=8519760 | doi = 10.1021/bi00049a018 | journal= Biochemistry}}</ref>

== Medical use ==
ATP is used intravenously for some heart related conditions.<ref>{{Cite journal|last1=Pelleg|first1=Amir|last2=Kutalek|first2=Steven P.|last3=Flammang|first3=Daniel|last4=Benditt|first4=David|date=February 2012|title=ATPace: injectable adenosine 5′-triphosphate|journal=Purinergic Signalling|volume=8|issue=Suppl 1|pages=57–60|doi=10.1007/s11302-011-9268-1|issn=1573-9538|pmc=3265710|pmid=22057692}}</ref>

==History==
ATP was discovered in 1929 by {{Interlanguage link|Karl Lohmann (biochemist)|lt=Karl Lohmann|de|Karl Lohmann (Biochemiker)}}<ref>{{cite journal |last=Lohmann |first=K. |title=Über die Pyrophosphatfraktion im Muskel |trans-title=On the pyrophosphate fraction in muscle |journal=Naturwissenschaften |volume=17 |issue=31 |pages=624–625 |date=August 1929 |doi=10.1007/BF01506215 |bibcode=1929NW.....17..624. |s2cid=20328411 |language=de}}</ref> and Jendrassik<ref>{{cite journal| title=The Determination of Phosphorus and the Discovery of Phosphocreatine and ATP: the Work of Fiske and SubbaRow| journal=Journal of Biological Chemistry| volume=277| issue=32| pages=e21| url=http://www.jbc.org/content/277/32/e21| year=2002| last1=Vaughan| first1=Martha| last2=Hill| first2=Robert L.| last3=Simoni| first3=Robert D.| pmid=12161449| access-date=2017-10-24| archive-url=https://web.archive.org/web/20170808062708/http://www.jbc.org/content/277/32/e21| archive-date=2017-08-08| url-status=live}}</ref> and, independently, by Cyrus Fiske and [[Yellapragada Subba Rao]] of [[Harvard Medical School]],<ref>{{cite journal |last=Maruyama |first=K. |title=The discovery of adenosine triphosphate and the establishment of its structure |journal=J. Hist. Biol. |volume=24 |issue=1 |pages=145–154 |date=March 1991 |doi=10.1007/BF00130477 |s2cid=87425890 }}</ref> both teams competing against each other to find an assay for phosphorus.

It was proposed to be the intermediary between energy-yielding and energy-requiring reactions in cells by [[Fritz Albert Lipmann]] in 1941.<ref>{{cite journal |last=Lipmann |first=F. |title=Metabolic generation and utilization of phosphate bond energy.  |journal=Adv. Enzymol. |volume=1 |pages=99–162 |year=1941 |issn=0196-7398}}</ref>

It was first synthesized in the laboratory by [[Alexander R. Todd, Baron Todd|Alexander Todd]] in 1948,<ref>{{cite web| url=http://nobelprize.org/nobel_prizes/chemistry/laureates/1997/illpres/history.html| work=The Nobel Prize in Chemistry 1997| title=History: ATP first discovered in 1929| publisher=[[Nobel Foundation]]| access-date=2010-05-26| archive-url=https://web.archive.org/web/20100123061355/http://nobelprize.org/nobel_prizes/chemistry/laureates/1997/illpres/history.html| archive-date=2010-01-23| url-status=live}}</ref> and he was awarded the [[Nobel Prize in Chemistry]] in 1957 partly for this work.

The 1978 [[Nobel Prize in Chemistry]] was awarded to [[Peter D. Mitchell|Peter Dennis Mitchell]] for the discovery of the [[Chemiosmosis|chemiosmotic]] mechanism of ATP synthesis.

The 1997 Nobel Prize in Chemistry was divided, one half jointly to [[Paul D. Boyer]] and [[John E. Walker]] "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)" and the other half to [[Jens C. Skou]] "for the first discovery of an ion-transporting enzyme, Na<sup>+</sup>, K<sup>+</sup> -ATPase."<ref>{{cite web|url=https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/|title=The Nobel Prize in Chemistry 1997|website=Nobel Prize |access-date=21 January 2018|archive-url=https://web.archive.org/web/20171024205633/https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/|archive-date=24 October 2017|url-status=live}}</ref>
{{clear}}

==See also==
{{col div|colwidth=30em}}
* [[Adenosine-tetraphosphatase]]
* [[NDPCP|Adenosine methylene triphosphate]]
* [[ATPases]]
* [[ATP test]]
* [[Creatine]]
* [[Cyclic adenosine monophosphate]] (cAMP)
* [[Nucleotide exchange factor]]
* [[Phosphagen]]
{{colend}}

==References==
{{Reflist|30em}}

==External links==
{{Commons category|Adenosine triphosphate}}
* [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=ATP ATP bound to proteins] in the [[Protein Data Bank|PDB]]
* [https://web.archive.org/web/20160310134410/http://www.scienceaid.co.uk/biology/biochemistry/atp.html ScienceAid: Energy ATP and Exercise]
* [https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5957 PubChem entry for Adenosine Triphosphate]
* [http://www.genome.jp/dbget-bin/www_bget?cpd:C00002 KEGG entry for Adenosine Triphosphate]

{{Nucleobases, nucleosides, and nucleotides}}
{{Enzyme cofactors}}
{{Neurotransmitters}}
{{Food science}}
{{Cellular respiration}}
{{MetabolismMap}}

{{Authority control}}

{{DEFAULTSORT:Adenosine phosphate3}}
[[Category:Adenosine receptor agonists]]
[[Category:Cellular respiration]]
[[Category:Coenzymes]]
[[Category:Ergogenic aids]]
[[Category:Exercise physiology]]
[[Category:Neurotransmitters]]
[[Category:Nucleotides]]
[[Category:Phosphate esters]]
[[Category:Purinergic signalling]]
[[Category:Purines]]
[[Category:Substances discovered in the 1920s]]