TheInfoList

organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...
and
hydrotropeA hydrotrope is a compound that solubilizes hydrophobic compounds in aqueous solutions by means other than micellar solubilization. Typically, hydrotropes consist of a hydrophilic part and a hydrophobic part (similar to surfactants), but the hydrop ...
that provides energy to drive many processes in living
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or cave in which a monk or religious recluse lives * Prison cell, a room used to hold peopl ...
, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of
currency A currency, "in circulation", from la, currens, -entis, literally meaning "running" or "traversing" in the most specific sense is money Money is any item or verifiable record that is generally accepted as payment for goods and services ...

" of intracellular
energy transfer In physics Physics is the natural science that studies matter, its Elementary particle, fundamental constituents, its Motion (physics), motion and behavior through Spacetime, space and time, and the related entities of energy and fo ...

. When consumed in
metabolic Metabolism (, from el, Î¼ÎµÏ„Î±Î²Î¿Î»Î® ''metabolÄ“'', "change") is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of the energy in food to energy available to run cell ...

processes such as
cellular respiration Cellular respiration is a set of metabolic Metabolism (, from el, Î¼ÎµÏ„Î±Î²Î¿Î»Î® ''metabolÄ“'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such a ...

, it converts either to
adenosine diphosphate Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of o ...

adenosine monophosphate Adenosine is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior ...
(AMP). Other processes regenerate ATP so that the human body recycles its own body weight equivalent in ATP each day. It is also a
precursor Precursor or Precursors may refer to: *Precursor (religion) In religion, a precursor, also known as forerunner, predecessor, harbinger or herald, is a holy person who announced the approaching appearance of a central figure of the religion or who ...
to DNA and RNA, and is used as a
coenzyme A cofactor is a non-protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 195 ...
. From the perspective of
biochemistry Biochemistry or biological chemistry, is the study of chemical process In a scientific Science () is a systematic enterprise that Scientific method, builds and organizes knowledge in the form of Testability, testable explanations and pr ...

, ATP is classified as a
nucleoside triphosphate Nucleosides are glycosylamine 120px, Cyclic hemiaminal ether bond derived from an aldehyde Glycosylamines are a class of biochemical compounds consisting of a Glycosyl, glycosyl group attached to an amine, amino group, -NR2. They are also known ...
, which indicates that it consists of three components: a nitrogenous base (
adenine Adenine (A, Ade) is a nucleobase 230px, Pyrimidine nucleobases are simple ring molecules. Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides Nucleos ...

), the sugar
ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition Hâˆ’(C=O)âˆ’(CHOH)4âˆ’H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compoun ...

, and the triphosphate.

# Structure

ATP consists of an
adenine Adenine (A, Ade) is a nucleobase 230px, Pyrimidine nucleobases are simple ring molecules. Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides Nucleos ...

attached by the 9-nitrogen atom to the 1â€² carbon atom of a sugar (
ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition Hâˆ’(C=O)âˆ’(CHOH)4âˆ’H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compoun ...

), 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 and AMP. The three phosphoryl groups are referred to as the alpha (Î±), beta (Î²), and, for the terminal phosphate, gamma (Î³). In neutral solution, ionized ATP exists mostly as ATP4âˆ’, with a small proportion of ATP3âˆ’.

## Binding of metal cations to ATP

Being polyanionic and featuring a potentially chelatable polyphosphate group, ATP binds metal cations with high affinity. The
binding constant The binding constant, or association constant, is a special case of the equilibrium constant The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemica ...
for is (). The binding of a
divalent In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo durin ...
cation An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are u ...
, almost always
magnesium Magnesium is a chemical element upright=1.0, 500px, The chemical elements ordered by link=Periodic table In chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science ...

, strongly affects the interaction of ATP with various proteins. Due to the strength of the ATP-Mg2+ interaction, ATP exists in the cell mostly as a complex with bonded to the phosphate oxygen centers. A second magnesium ion is critical for ATP binding in the kinase domain. The presence of Mg2+ regulates kinase activity.

# Chemical properties

Salts of ATP can be isolated as colorless solids. ATP is stable in aqueous solutions between pH 6.8 and 7.4, in the absence of catalysts. At more extreme pHs, it rapidly
hydrolyses Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

to 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. In the context of biochemical reactions, the P-O-P bonds are frequently referred to as ''high-energy bonds''. The hydrolysis of ATP into ADP and inorganic phosphate releases 30.5
kJ/mol The joule per mole (symbol: JÂ·molâˆ’1 or J/mol) is an SI derived unit SI derived units are units of measurement ' Measurement is the number, numerical quantification (science), quantification of the variable and attribute (research), attributes o ...
of enthalpy, with a change in free energy of 3.4 kJ/mol. The energy released by cleaving either a phosphate (Pi) or pyrophosphate (PPi) unit from ATP at
standard state In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in t ...
of 1 M are: :ATP + â†’ ADP + Pi Î”''G''Â° = âˆ’30.5 kJ/mol (âˆ’7.3 kcal/mol) :ATP + â†’ AMP + PPi Î”''G''Â° = âˆ’45.6 kJ/mol (âˆ’10.9 kcal/mol) These abbreviated equations can be written more explicitly (R = ): : O-P(O)2-O-P(O)2-O-PO3sup>4âˆ’ + â†’ O-P(O)2-O-PO3sup>3âˆ’ + O4sup>3âˆ’ + 2 H+ : O-P(O)2-O-P(O)2-O-PO3sup>4âˆ’ + â†’ O-PO3sup>2âˆ’ + 3P-O-PO3sup>4âˆ’ + 2 H+

# Production from AMP and ADP

## Production, aerobic conditions

A typical intracellular
concentration In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in t ...

of ATP is hard to pin down, however, reports have shown there to be 1â€“10  Î¼mol per gram of tissue in a variety of eukaryotes. The dephosphorylation of ATP and rephosphorylation of ADP and AMP occur repeatedly in the course of aerobic metabolism. ATP can be produced by a number of distinct cellular processes; the three main pathways in
eukaryote Eukaryotes () are organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interact ...

s are (1)
glycolysis Glycolysis is the metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of on ...

, (2) the
citric acid cycle The citric acid cycle (CAC) â€“ also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle â€“ is a series of chemical reactions to release stored energy through the redox, oxidation of acetyl-CoA derived from carbohydra ...

/
oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), c ...

, and (3)
beta-oxidation 350px, Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, LCHAD deficiency In biochemistry an ...
. The overall process of oxidizing glucose to
carbon dioxide Carbon dioxide (chemical formula A chemical formula is a way of presenting information about the chemical proportions of s that constitute a particular or molecule, using symbols, numbers, and sometimes also other symbols, such as pare ...

, the combination of pathways 1 and 2, known as
cellular respiration Cellular respiration is a set of metabolic Metabolism (, from el, Î¼ÎµÏ„Î±Î²Î¿Î»Î® ''metabolÄ“'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such a ...

, produces about 30 equivalents of ATP from each molecule of glucose. ATP production by a non-
photosynthetic Photosynthesis is a process used by plants and other organisms to convert Conversion or convert may refer to: Arts, entertainment, and media * Conversion (Doctor Who audio), "Conversion" (''Doctor Who'' audio), an episode of the audio drama ' ...
aerobic eukaryote occurs mainly in the
mitochondria A mitochondrion (; ) is a double-membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...

, which comprise nearly 25% of the volume of a typical cell.

### Glycolysis

In glycolysis, glucose and glycerol are metabolized to
pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to an R-group. The general formula of a carboxylic acid is Râˆ ...

. Glycolysis generates two equivalents of ATP through substrate phosphorylation catalyzed by two enzymes, and
pyruvate kinase Pyruvate kinase is the enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the e ...

. Two equivalents of
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
are also produced, which can be oxidized via the
electron transport chain An electron transport chain (ETC) is a series of protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chain Peptides (from Greek language Greek (modern , romanized: ''EllinikÃ¡'', Anc ...

and result in the generation of additional ATP by
ATP synthase ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation of ...

. The pyruvate generated as an end-product of glycolysis is a substrate for the
Krebs Cycle The citric acid cycle (CAC) â€“ also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle â€“ is a series of chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set o ...

. 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.

### =Regulation

= In glycolysis,
hexokinase A hexokinase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the e ...
is directly inhibited by its product, glucose-6-phosphate, and
pyruvate kinase Pyruvate kinase is the enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the e ...

is inhibited by ATP itself. The main control point for the glycolytic pathway is
phosphofructokinase Phosphofructokinase (PFK) is a kinase In biochemistry Biochemistry or biological chemistry, is the study of chemical process In a scientific Science () is a systematic enterprise that Scientific method, builds and organizes kno ...
(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 A tetramer () (''wikt:tetra-, tetra-'', "four" + ''wikt:-mer, -mer'', "parts") is an oligomer formed from four monomers or Protein subunit, subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium ...
that exists in two conformations, only one of which binds the second substrate fructose-6-phosphate (F6P). The protein has two
binding site Binding may refer to: Computing * Binding, associating a network socket Network and networking may refer to: Arts, entertainment, and media * Network (1976 film), ''Network'' (1976 film), a 1976 American film * Network (2019 film), ''Network'' ...
s for ATP â€“ the
active site Active may refer to: Music * ''Active'' (album), a 1992 album by Casiopea * Active Records Active Records was a record label, record sublabel of RCA Records founded in 1980. The label focused mainly on heavy metal music. The label was disso ...

is accessible in either protein conformation, but ATP binding to the inhibitor site stabilizes the conformation that binds F6P poorly. A number of other small molecules can compensate for the ATP-induced shift in equilibrium conformation and reactivate PFK, including
cyclic AMP Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...
,
ammonium The ammonium cation An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects t ...

ions, inorganic phosphate, and fructose-1,6- and -2,6-biphosphate.

### Citric acid cycle

In the
mitochondrion A mitochondrion (; ) is a double-membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...

, pyruvate is oxidized by the
pyruvate dehydrogenase complex Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this ...
to the
acetyl In organic chemistry Organic chemistry is a branch of that studies the structure, properties and reactions of s, which contain in .Clayden, J.; Greeves, N. and Warren, S. (2012) ''Organic Chemistry''. Oxford University Press. pp. 1â€“15. . ...

group, which is fully oxidized to
carbon dioxide Carbon dioxide (chemical formula A chemical formula is a way of presenting information about the chemical proportions of s that constitute a particular or molecule, using symbols, numbers, and sometimes also other symbols, such as pare ...

by the
citric acid cycle The citric acid cycle (CAC) â€“ also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle â€“ is a series of chemical reactions to release stored energy through the redox, oxidation of acetyl-CoA derived from carbohydra ...

(also known as the Krebs cycle). Every "turn" of the citric acid cycle produces two molecules of carbon dioxide, one equivalent of ATP
guanosine triphosphate Guanosine-5'-triphosphate (GTP) is a purine Purine is a heterocyclic 125px, Pyridine, a heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elemen ...
(GTP) through
substrate-level phosphorylation Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armeni ...
catalyzed by succinyl-CoA synthetase, as succinyl- CoA is converted to Succinate, three equivalents of
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
FAD A fad is any form of collective behavior The expression collective behavior was first used by Franklin Henry Giddings Franklin Henry Giddings (March 23, 1855 â€“ June 11, 1931) was an American sociologist and economist An econ ...

, respectively), generating additional ATP by
oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), c ...

. The oxidation of NADH results in the synthesis of 2â€“3 equivalents of ATP, and the oxidation of one FADH2 yields between 1â€“2 equivalents of ATP. The majority of cellular ATP is generated by this process. Although the citric acid cycle itself does not involve molecular
oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the chemical elements In chemistry, an element is a pure substance consisting only of atoms that all have the same ...

, it is an obligately
aerobic Aerobic means "requiring Earth's atmosphere, air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Cellular respiration#Aerobic r ...
process because O2 is used to recycle the NADH and FADH2 and provides the chemical energy driving the process. In the absence of oxygen, the citric acid cycle ceases. The generation of ATP by the mitochondrion from cytosolic NADH relies on the
malate-aspartate shuttle The malate-aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOOâˆ’, and a ...

(and to a lesser extent, the glycerol-phosphate shuttle) because the inner mitochondrial membrane is impermeable to NADH and NAD+. Instead of transferring the generated NADH, a malate dehydrogenase enzyme converts
oxaloacetate Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemi ...

to
malate Malic acid is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavi ...
, 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+. A
transaminase Transaminases or aminotransferases are enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , ...
converts the oxaloacetate to aspartate for transport back across the membrane and into the intermembrane space. In oxidative phosphorylation, the passage of electrons from NADH and FADH2 through the electron transport chain releases the chemical energy of O2 to pump
proton A proton is a subatomic particle, symbol or , with a positive electric charge of +1''e'' elementary charge and a mass slightly less than that of a neutron. Protons and neutrons, each with masses of approximately one atomic mass unit, are collecti ...

s out of the mitochondrial matrix and into the intermembrane space. This pumping generates a
proton motive forceChemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient An electrochemical gradient is a gradient In vector calculus, the gradient of a scalar-valued function, scalar-valued dif ...
that is the net effect of a gradient and an
electric potential The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is defined as the amount of work Work may refer to: * Work (human activity), intentional activity people perform to support the ...

gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient â€“ that is, from the intermembrane space to the matrix â€“ yields ATP by
ATP synthase ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation of ...

. Three ATP are produced per turn. Although oxygen consumption appears fundamental for the maintenance of the
proton motive forceChemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient An electrochemical gradient is a gradient In vector calculus, the gradient of a scalar-valued function, scalar-valued dif ...
, in the event of oxygen shortage ( hypoxia), intracellular acidosis (mediated by enhanced glycolytic rates and ATP hydrolysis), contributes to mitochondrial membrane potential and directly drives ATP synthesis. 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+. Producing one ATP costs about 3 H+. Therefore, making and exporting one ATP requires 4H+. The inner membrane contains an
antiporter An antiporter (also called exchanger or counter-transporter) is a cotransporterCotransporters are a subcategory of membrane transport protein A membrane transport protein (or simply transporter) is a membrane protein Membrane proteins are commo ...

, the /ATP translocase, which is an
integral membrane protein An integral membrane protein (IMP) is a type of membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. I ...
used to exchange newly synthesized ATP in the matrix for in the intermembrane space. This translocase is driven by the membrane potential, as it results in the movement of about 4 negative charges out across the mitochondrial membrane in exchange for 3 negative charges moved inside. However, it is also necessary to transport phosphate into the mitochondrion; the phosphate carrier moves a proton in with each phosphate, partially dissipating the proton gradient. After completing glycolysis, the citric acid cycle, the electron transport chain, and oxidative phosphorylation, approximately 30â€“38 ATP molecules are produced per glucose.

### =Regulation

= The citric acid cycle is regulated mainly by the availability of key substrates, particularly the ratio of NAD+ to NADH and the concentrations of
calcium Calcium is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical elem ...

, inorganic phosphate, ATP, , and AMP.
Citrate Citric acid is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behav ...
â€“ the ion that gives its name to the cycle â€“ is a feedback inhibitor of
citrate synthase The enzyme citrate synthase Enzyme Commission number, E.C. 2.3.3.1 (previously 4.1.3.7)] exists in nearly all living cells and stands as a pace-making enzyme in the first step of the citric acid cycle (or Krebs cycle). Citrate synthase is localized ...

and also inhibits PFK, providing a direct link between the regulation of the citric acid cycle and glycolysis.

### Beta oxidation

In the presence of air and various cofactors and enzymes, fatty acids are converted to
acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reaction Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organism In biology, an organism (from ...

. The pathway is called
beta-oxidation 350px, Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, LCHAD deficiency In biochemistry an ...
. Each cycle of beta-oxidation shortens the fatty acid chain by two carbon atoms and produces one equivalent each of acetyl-CoA, NADH, and FADH2. The acetyl-CoA is metabolized by the citric acid cycle to generate ATP, while the NADH and FADH2 are used by oxidative phosphorylation to generate ATP. Dozens of ATP equivalents are generated by the beta-oxidation of a single long acyl chain.

### =Regulation

= In oxidative phosphorylation, the key control point is the reaction catalyzed by
cytochrome c oxidase The enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the ...
, which is regulated by the availability of its substrate â€“ the reduced form of
cytochrome c The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion A mitochondrion (; ) is a double-membrane Image:Schematic size.jpg, up150px, Schematic of size-based membra ...

. The amount of reduced cytochrome c available is directly related to the amounts of other substrates: : which directly implies this equation: :$\frac = \left\left(\frac\right\right)^\left\left(\frac\right\right)K_\mathrm$ Thus, a high ratio of to AD+or a high ratio of Pi] to imply a high amount of reduced cytochrome c and a high level of cytochrome c oxidase activity. An additional level of regulation is introduced by the transport rates of ATP and NADH between the mitochondrial matrix and the cytoplasm.

### Ketosis

Ketone bodies can be used as fuels, yielding 22 ATP and 2 GTP molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the
liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's t ...

to other tissues, where
acetoacetate Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound ...
and ''beta''-hydroxybutyrate can be reconverted to
acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reaction Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organism In biology, an organism (from ...

citric acid cycle The citric acid cycle (CAC) â€“ also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle â€“ is a series of chemical reactions to release stored energy through the redox, oxidation of acetyl-CoA derived from carbohydra ...

. Ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme Î²-ketoacyl-CoA transferase, also called
thiolase Thiolases, also known as acetyl-coenzyme A acetyltransferases (ACAT), are enzymes which convert two units of acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reaction Biochemistry or biologica ...
.
Acetoacetate Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound ...
in low concentrations is taken up by the liver and undergoes detoxification through the methylglyoxal pathway which ends with lactate.
Acetoacetate Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound ...
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.

## Production, anaerobic conditions

Fermentation Fermentation is a metabolic Metabolism (, from el, Î¼ÎµÏ„Î±Î²Î¿Î»Î® ''metabolÄ“'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such as Cell signalin ...
is the metabolism of organic compounds in the absence of air. It involves
substrate-level phosphorylation Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armeni ...
in the absence of a respiratory
electron transport chain An electron transport chain (ETC) is a series of protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chain Peptides (from Greek language Greek (modern , romanized: ''EllinikÃ¡'', Anc ...

. The equation for the reaction of glucose to form
lactic acid Lactic acid is an organic acid An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group â€“COOH. Sulfonic acids, conta ...

is: : + 2 ADP + 2 Pi â†’ 2  + 2 ATP + 2
Anaerobic respiration Anaerobic respiration is respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenan ...
is respiration in the absence of . Prokaryotes can utilize a variety of electron acceptors. These include
nitrate Nitrate is a polyatomic ion A polyatomic ion, also known as a molecular ion, is a covalently bonded A covalent bond is a chemical bond A chemical bond is a lasting attraction between atoms, ions or molecules that enables the format ...

,
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, 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 kinases (NDKs), which use other nucleoside triphosphates as a high-energy phosphate donor, and the ATP:guanido-phosphotransferase family.

## 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. 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 0.2 Mole (unit), moles. The majority of ATP is recycled from by the aforementioned processes. Thus, at any given time, the total amount of ATP + remains fairly constant. The energy used by human cells in an adult requires the hydrolysis of 100 to 150 moles of ATP daily, which is around 50 to 75 kg. A human will typically use up their body weight of ATP over the course of the day. Each equivalent of ATP is recycled 1000â€“1500 times during a single day ().

# 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. Phosphorylation of a protein by a kinase can activate a cascade such as the mitogen-activated protein kinase cascade. ATP is also a substrate of adenylate cyclase, most commonly in G proteinâ€“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. 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.

## DNA and RNA synthesis

ATP is one of four monomers required in the synthesis of RNA. The process is promoted by RNA polymerases. 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

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 âŸ¶ aa-AMP + pyrophosphate, PPi # aa-AMP + tRNA âŸ¶ aa-tRNA + AMP The amino acid is coupled to the penultimate nucleotide at the 3â€²-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 transporters. The human genome encodes 48 ABC transporters, that are used for exporting drugs, lipids, and other compounds.

## Extracellular signalling and neurotransmision

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 or is pumped into vesicles which then exocytosis, fuse with the membrane. Cells detect ATP using the purinergic receptor proteins P2X and P2Y.

## Protein solubility

ATP has recently been proposed to act as a biological
hydrotropeA hydrotrope is a compound that solubilizes hydrophobic compounds in aqueous solutions by means other than micellar solubilization. Typically, hydrotropes consist of a hydrophilic part and a hydrophobic part (similar to surfactants), but the hydrop ...
and has been shown to affect proteome-wide solubility.

# 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. Enzyme inhibitors of ATP-dependent enzymes such as kinases are needed to examine the
binding site Binding may refer to: Computing * Binding, associating a network socket Network and networking may refer to: Arts, entertainment, and media * Network (1976 film), ''Network'' (1976 film), a 1976 American film * Network (2019 film), ''Network'' ...
s and transition states involved in ATP-dependent reactions. 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 5â€²-(Î³-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.

# Medical use

ATP is used intravenously for some heart related conditions.

# History

ATP was discovered in 1929 by w:de:Karl Lohmann (Biochemiker), Karl Lohmann and Jendrassik and, independently, by Cyrus Fiske and Yellapragada Subba Rao of Harvard Medical School, 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. It was first synthesized in the laboratory by Alexander R. Todd, Baron Todd, Alexander Todd in 1948. The Nobel Prize in Chemistry 1997 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+, K+ -ATPase''."

* Adenosine diphosphate (ADP) * Adenosine monophosphate (AMP) * Adenosine-tetraphosphatase * NDPCP, Adenosine methylene triphosphate * ATPases * ATP test * ATP hydrolysis * Citric acid cycle (also called the Krebs cycle or TCA cycle) * Creatine * Cyclic adenosine monophosphate (cAMP) * Nucleotide exchange factor * Phosphagen * Photophosphorylation