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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-.

StatPearls [Internet].

Show detailsTreasure Island (FL): StatPearls Publishing; 2026 Jan-.Search term Physiology, Adenosine Triphosphate

Jacob Dunn; Michael H. Grider.

Author Information and Affiliations

Authors

Jacob Dunn1; Michael H. Grider2.

Affiliations

1 High Point University2 High Point University

Last Update: February 13, 2023.

Introduction

The body is a complex organism, and as such, it takes energy to maintain proper functioning. Adenosine triphosphate (ATP) is the primary energy source for cellular energy use and storage. The structure of ATP is a nucleoside triphosphate, consisting of a nitrogenous base (adenine), a ribose sugar, and 3 serially bonded phosphate groups. ATP is commonly referred to as the "energy currency" of the cell, as it provides readily releasable energy in the bond between the second and third phosphate groups. In addition to providing energy, ATP hydrolysis supports a broad range of cellular functions, including signaling and DNA/RNA synthesis. ATP synthesis utilizes energy obtained from multiple catabolic mechanisms, including cellular respiration, beta-oxidation, and ketosis.

The majority of ATP synthesis occurs during cellular respiration in the mitochondrial matrix, generating approximately 32 ATP molecules per glucose molecule oxidized. ATP is consumed for energy in processes including ion transport, muscle contraction, nerve impulse propagation, substrate phosphorylation, and chemical synthesis. These processes, among others, create a high demand for ATP. As a result, cells in the human body depend on the hydrolysis of 100-150 moles of ATP per day to ensure proper functioning. In the following sections, ATP is further evaluated for its role as a central molecule in cellular function.

Cellular Level

ATP is an excellent energy-storage molecule to use as a "currency" due to the phosphate groups linked by phosphodiester bonds. These bonds are high-energy because the electronegative charges exert a repulsive force between phosphate groups. A significant quantity of energy remains stored within the phosphate-phosphate bonds. Through metabolic processes, ATP is hydrolyzed to ADP, then to AMP, and finally to free inorganic phosphate. The hydrolysis of ATP to ADP is energetically favorable, yielding a Gibbs free energy change of -7.3 cal/mol.[1] ATP must be continuously replenished to fuel the ever-active cell. The routine intracellular ATP concentration is 1-10 μM.[2] Many feedback mechanisms are in place to maintain a consistent ATP level in the cell. The enhancement or inhibition of ATP synthase is a common regulatory mechanism. For example, ATP inhibits phosphofructokinase-1 (PFK1) and pyruvate kinase, 2 key enzymes in glycolysis, thereby acting as a negative feedback loop that inhibits glucose breakdown when cellular ATP is sufficient.

Conversely, ADP and AMP can activate PFK1 and pyruvate kinase, thereby promoting ATP synthesis during periods of high-energy demand. Other systems regulate ATP, including mechanisms that control ATP synthesis in the heart. Novel experiments have demonstrated that 10-second bursts called mitochondrial flashes can disrupt ATP production in the heart. During these mitochondrial flashes, the mitochondria release reactive oxygen species and effectively pause ATP synthesis. ATP production inhibition occurs during mitochondrial flashes. During periods of low energy demand, when heart muscle cells received sufficient building blocks to produce ATP, mitochondrial flashes were observed more frequently. Alternatively, when energy demand is high during rapid heart contraction, mitochondrial flashes occur less often. These results suggested that during periods when substantial ATP is required, mitochondrial flashes occur less frequently to maintain ATP production. Conversely, during times of low energy output, mitochondrial flashes occurred more regularly and inhibited ATP production.[3]

Function

ATP hydrolysis provides the energy needed for many essential processes in organisms and cells. These include intracellular signaling, DNA and RNA synthesis, Purinergic signaling, synaptic signaling, active transport, and muscle contraction. These topics are not an exhaustive list but rather include some of the vital roles that ATP plays.

ATP in Intracellular Signaling

Signal transduction heavily relies on ATP. ATP can serve as a substrate for kinases, the most numerous ATP-binding proteins. When a kinase phosphorylates a protein, a signaling cascade can be activated, thereby modulating diverse intracellular signaling pathways.[4] Kinase activity is vital to the cell and, therefore, must be tightly regulated. The presence of the magnesium ion helps regulate kinase activity.[5] Regulation is through magnesium ions existing in the cell as a complex with ATP, bound at the phosphate oxygen centers. In addition to its role in kinase activity, ATP can serve as a ubiquitous trigger for the release of intracellular messengers.[6] These messengers include hormones, various enzymes, lipid mediators, neurotransmitters, nitric oxide, growth factors, and reactive oxygen species.[6] An example of ATP utilization in intracellular signaling is its use as a substrate for adenylate cyclase. This process mostly occurs in G-protein-coupled receptor signaling pathways. Upon binding to adenylate cyclase, ATP converts to cyclic AMP, which assists in signaling the release of calcium from intracellular stores.[7] cAMP has other roles, including serving as a secondary messenger in hormone signaling cascades, activating protein kinases, and regulating the function of ion channels. 

DNA/RNA Synthesis

DNA and RNA synthesis require ATP. ATP is 1 of 4 nucleotide-triphosphate monomers that are necessary during RNA synthesis. DNA synthesis uses a similar mechanism, except that, in DNA synthesis, ATP is converted by removing an oxygen atom from the sugar to yield the deoxyribonucleotide dATP.[8]

Purinergic Signaling

Purinergic signaling is a form of extracellular paracrine signaling that is mediated by purine nucleotides, including ATP. This process commonly entails the activation of purinergic receptors on cells within proximity, thereby transducing signals to regulate intracellular processes. ATP is released from vesicular stores and is regulated by IP3 and other common exocytotic regulatory mechanisms. ATP is co-stored and co-released among neurotransmitters, further supporting the notion that ATP is a necessary mediator of purinergic neurotransmission in both sympathetic and parasympathetic nerves. ATP can induce several purinergic responses, including control of autonomic functions, neural glia interactions, pain, and control of vessel tone.[9][10][11][12] 

Neurotransmission

The brain is the body's highest consumer of ATP, accounting for approximately 25% of total energy expenditure.[13] A substantial amount of energy is expended on maintaining ion concentrations required for proper neuronal signaling and synaptic transmission.[14] Synaptic transmission is an energy-demanding process. At the presynaptic terminal, ATP is required for establishing ion gradients that shuttle neurotransmitters into vesicles and for priming the vesicles for release through exocytosis.[14]Neuronal signaling depends on the action potential reaching the presynaptic terminal, thereby triggering the release of the vesicles loaded with neurotransmitters. This process depends on ATP restoring the ion concentration in the axon after each action potential, thereby enabling the next action potential. Active transport is responsible for resetting the sodium and potassium ion concentrations to baseline values after an action potential via the Na/K ATPase. During this process, 1 ATP molecule is hydrolyzed, 3 sodium ions are transported out of the cell, and 2 potassium ions are transported back into the cell, all against their concentration gradients.

Action potentials traveling down the axon initiate vesicular release upon reaching the presynaptic terminal. After establishing the ion gradients, action potentials propagate down the axon via depolarization, sending a signal toward the terminal. Approximately 1 billion sodium ions are necessary to propagate a single action potential. Neurons need to hydrolyze nearly 1 billion ATP molecules to restore the sodium/potassium ion concentration after each cell depolarization.[13]Excitatory synapses largely dominate the grey matter of the brain. Vesicles containing glutamate are released into the synaptic cleft to activate postsynaptic excitatory glutaminergic receptors. Loading these molecules requires substantial ATP, given that nearly 4 thousand glutamate molecules are stored in a single vesicle.[13] Significant stores of energy are necessary to initiate the release of the vesicle, drive the glutamatergic postsynaptic processes, and recycle the vesicle as well as the leftover glutamate.[13] Therefore, due to the large amounts of energy required for glutamate packing, mitochondria are close to glutamatergic vesicles.[15]

ATP in Muscle Contraction

Muscle contraction is a necessary function of everyday life and could not occur without ATP. There are 3 primary roles that ATP plays in muscle contraction. The first is through the generation of force against adjoining actin filaments through the cycling of myosin cross-bridges. The second is the pumping of calcium ions from the myoplasm into the sarcoplasmic reticulum against their concentration gradient via active transport. The third function of ATP is the active transport of sodium and potassium ions across the sarcolemma, thereby enabling calcium ion release upon input. The hydrolysis of ATP drives each of these processes.[16]

Mechanism

Many processes can produce ATP in the body, depending on the prevailing metabolic conditions. ATP can be produced by cellular respiration, beta-oxidation, ketosis, lipid and protein catabolism, and under anaerobic conditions.

Cellular Respiration

Cellular respiration is the process of catabolizing glucose into acetyl-CoA, producing high-energy electron carriers that are oxidized during oxidative phosphorylation, thereby generating ATP. During glycolysis, the first step in cellular respiration, 1 glucose molecule is converted into 2 pyruvate molecules. During this process, 2 ATP are produced through substrate phosphorylation by the enzymes PFK1 and pyruvate kinase. There is also the production of 2 reduced NADH electron carrier molecules. The pyruvate molecules are then oxidized by the pyruvate dehydrogenase complex, yielding acetyl-CoA. The acetyl-CoA molecule is then fully oxidized to yield carbon dioxide and reduced electron carriers in the citric acid cycle. Upon completing the citric acid cycle, the total yield is 2 molecules of carbon dioxide, 1 equivalent of ATP, 3 molecules of NADH, and 1 molecule of FADH2. These high-energy electron carriers then transfer electrons to the electron transport chain, in which hydrogen ions (protons) are transported against their electrochemical gradient into the inner mitochondrial membrane space from the mitochondrial matrix. ATP molecules are then synthesized as protons move down the electrochemical gradient through ATP synthase.[9] The amount of ATP produced depends on which electron carrier donates protons. One NADH molecule produces 2 and a half ATP, whereas 1 FADH2 molecule produces 1 and a half ATP molecules.[17]

Beta-Oxidation

Beta-oxidation is another mechanism for ATP synthesis in organisms. During beta-oxidation, fatty acid chains are permanently shortened, yielding Acetyl-CoA molecules. Throughout each cycle of beta-oxidation, the fatty acid is reduced by 2 carbon lengths, producing 1 molecule of acetyl-CoA, which can be oxidized in the citric acid cycle, and 1 molecule each of NADH and FADH2, which transfer their high-energy electrons to the transport chain.[18]

Ketosis

Ketosis is a reaction that yields ATP through the catabolism of ketone bodies. During ketosis, ketone bodies undergo catabolism to produce energy, generating 22 ATP molecules and 2 GTP molecules per acetoacetate molecule that is oxidized in the mitochondria.

Anaerobic Respiration

When oxygen is scarce or unavailable during cellular respiration, cells can undergo anaerobic respiration. Under anaerobic conditions, NADH accumulates because NADH cannot be oxidized to NAD+, thereby limiting GAPDH activity and glucose consumption. To maintain homeostatic NADH levels, pyruvate is reduced to lactate, thereby oxidizing 1 NADH molecule in a process known as lactic fermentation. In lactic fermentation, the 2 molecules of NADH created in glycolysis are oxidized to maintain the NAD+ reservoir. This reaction produces only 2 ATP molecules per glucose molecule. 

Related Testing

Many methods can be used to measure intracellular ATP levels. A commonly accepted protocol involves using firefly luciferase, an enzyme that catalyzes the oxidation of luciferin.[19] This reaction is quantifiable because it releases a photon of light (bioluminescence).

Clinical Significance

ATP's Role in Pain Control

ATP has been shown to reduce acute perioperative pain in clinical studies.[20] In these studies, patients received intravenous ATP. The intravenous adenosine infusion acts on the A1 adenosine receptor, initiating a signaling cascade that ultimately contributes to the pain-relieving effects observed during inflammation. Studies have shown that adenosine compounds decrease allodynia and hyperalgesia when administered in moderate doses.[20] A1 adenosine receptor activation enables effective pain intervention by delivering a slow onset and a long duration of action, potentially lasting for weeks in some cases.[20]

Anesthesia

ATP supplementation produced positive outcomes during anesthesia. Evidence shows that low doses of adenosine reduce neuropathic pain, ischemic pain, and hyperalgesia to a level comparable to morphine.[21] Adenosine also decreased postoperative opioid usage, suggesting a potential long-lasting A1 adenosine receptor activation.

Cardiology and Surgery

ATP has been demonstrated to be a safe and practical pulmonary vasodilator in patients affected by pulmonary hypertension.[21] Similarly, adenosine and ATP can be employed during surgery to induce hypotension in patients.[21]

Review Questions

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References

1.Meurer F, Do HT, Sadowski G, Held C. Standard Gibbs energy of metabolic reactions: II. Glucose-6-phosphatase reaction and ATP hydrolysis. Biophys Chem. 2017 Apr;223:30-38. [PubMed: 28282626]2.Beis I, Newsholme EA. The contents of adenine nucleotides, phosphagens and some glycolytic intermediates in resting muscles from vertebrates and invertebrates. Biochem J. 1975 Oct;152(1):23-32. [PMC free article: PMC1172435] [PubMed: 1212224]3.Wang X, Zhang X, Wu D, Huang Z, Hou T, Jian C, Yu P, Lu F, Zhang R, Sun T, Li J, Qi W, Wang Y, Gao F, Cheng H. Mitochondrial flashes regulate ATP homeostasis in the heart. Elife. 2017 Jul 10;6 [PMC free article: PMC5503511] [PubMed: 28692422]4.Mishra NS, Tuteja R, Tuteja N. Signaling through MAP kinase networks in plants. Arch Biochem Biophys. 2006 Aug 01;452(1):55-68. [PubMed: 16806044]5.Lin X, Ayrapetov MK, Sun G. Characterization of the interactions between the active site of a protein tyrosine kinase and a divalent metal activator. BMC Biochem. 2005 Nov 23;6:25. [PMC free article: PMC1316873] [PubMed: 16305747]6.Zimmermann H. Extracellular ATP and other nucleotides-ubiquitous triggers of intercellular messenger release. Purinergic Signal. 2016 Mar;12(1):25-57. [PMC free article: PMC4749530] [PubMed: 26545760]7.Kamenetsky M, Middelhaufe S, Bank EM, Levin LR, Buck J, Steegborn C. Molecular details of cAMP generation in mammalian cells: a tale of two systems. J Mol Biol. 2006 Sep 29;362(4):623-39. [PMC free article: PMC3662476] [PubMed: 16934836]8.Joyce CM, Steitz TA. Polymerase structures and function: variations on a theme? J Bacteriol. 1995 Nov;177(22):6321-9. [PMC free article: PMC177480] [PubMed: 7592405]9.Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski JM, Bononi A, Giorgi C, Marchi S, Missiroli S, Poletti F, Wieckowski MR, Pinton P. ATP synthesis and storage. Purinergic Signal. 2012 Sep;8(3):343-57. [PMC free article: PMC3360099] [PubMed: 22528680]10.Cárdenas C, Miller RA, Smith I, Bui T, Molgó J, Müller M, Vais H, Cheung KH, Yang J, Parker I, Thompson CB, Birnbaum MJ, Hallows KR, Foskett JK. Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria. Cell. 2010 Jul 23;142(2):270-83. [PMC free article: PMC2911450] [PubMed: 20655468]11.Pablo Huidobro-Toro J, Verónica Donoso M. Sympathetic co-transmission: the coordinated action of ATP and noradrenaline and their modulation by neuropeptide Y in human vascular neuroeffector junctions. Eur J Pharmacol. 2004 Oct 01;500(1-3):27-35. [PubMed: 15464018]12.Coco S, Calegari F, Pravettoni E, Pozzi D, Taverna E, Rosa P, Matteoli M, Verderio C. Storage and release of ATP from astrocytes in culture. J Biol Chem. 2003 Jan 10;278(2):1354-62. [PubMed: 12414798]13.Attwell D, Laughlin SB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab. 2001 Oct;21(10):1133-45. [PubMed: 11598490]14.Harris JJ, Jolivet R, Attwell D. Synaptic energy use and supply. Neuron. 2012 Sep 06;75(5):762-77. [PubMed: 22958818]15.Wong-Riley MT. Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trends Neurosci. 1989 Mar;12(3):94-101. [PubMed: 2469224]16.Barclay CJ. Energetics of contraction. Compr Physiol. 2015 Apr;5(2):961-95. [PubMed: 25880520]17.Rich PR. The molecular machinery of Keilin's respiratory chain. Biochem Soc Trans. 2003 Dec;31(Pt 6):1095-105. [PubMed: 14641005]18.Ronnett GV, Kim EK, Landree LE, Tu Y. Fatty acid metabolism as a target for obesity treatment. Physiol Behav. 2005 May 19;85(1):25-35. [PubMed: 15878185]19.Brovko LYu, Romanova NA, Ugarova NN. Bioluminescent assay of bacterial intracellular AMP, ADP, and ATP with the use of a coimmobilized three-enzyme reagent (adenylate kinase, pyruvate kinase, and firefly luciferase). Anal Biochem. 1994 Aug 01;220(2):410-4. [PubMed: 7978286]20.Hayashida M, Fukuda K, Fukunaga A. Clinical application of adenosine and ATP for pain control. J Anesth. 2005;19(3):225-35. [PubMed: 16032451]21.Agteresch HJ, Dagnelie PC, van den Berg JW, Wilson JH. Adenosine triphosphate: established and potential clinical applications. Drugs. 1999 Aug;58(2):211-32. [PubMed: 10473017]

Disclosure: Jacob Dunn declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Grider declares no relevant financial relationships with ineligible companies.

Copyright © 2026, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

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• Cite this PageDunn J, Grider MH. Physiology, Adenosine Triphosphate. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-.

In this Page

• Introduction
• Cellular Level
• Function
• Mechanism
• Related Testing
• Clinical Significance
• Review Questions
• References

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