TheInfoList

OR:

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon chemical bond, bonds. Due to carbon's ability to Catenation, catenate (form chains with other carbon atoms), millions of organic c ...
that provides
energy In physics, energy (from Ancient Greek: wikt:ἐνέργεια#Ancient_Greek, ἐνέργεια, ''enérgeia'', “activity”) is the physical quantity, quantitative physical property, property that is #Energy transfer, transferred to a phy ...
to drive many processes in living cells, such as
muscle contraction Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscl ...
,
nerve impulse An action potential occurs when the membrane potential of a specific Cell (biology), cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of ...
propagation, condensate dissolution, and chemical synthesis. Found in all known forms of
life Life is a quality that distinguishes matter that has biological processes, such as Cell signaling, signaling and self-sustaining processes, from that which does not, and is defined by the capacity for Cell growth, growth, reaction to Stimu ...
, ATP is often referred to as the "molecular unit of
currency A currency, "in circulation", from la, Wikt:currens, currens, -entis, literally meaning "running" or "traversing" is a standardization of money in any form, in use or currency in circulation, circulation as a medium of exchange, for example ba ...
" of intracellular
energy transfer In physics, energy (from Ancient Greek: wikt:ἐνέργεια#Ancient_Greek, ἐνέργεια, ''enérgeia'', “activity”) is the physical quantity, quantitative physical property, property that is #Energy transfer, transferred to a phy ...
. When consumed in
metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
processes, it converts either to
adenosine diphosphate Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells (biology), cells. ADP consists of three important structural components: ...
adenosine monophosphate Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine; it is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it t ...
(AMP). Other processes regenerate ATP. The
human body The human body is the structure of a Human, human being. It is composed of many different types of Cell (biology), cells that together create Tissue (biology), tissues and subsequently organ systems. They ensure homeostasis and the life, viabi ...
recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme. From the perspective of
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology a ...
, ATP is classified as a
nucleoside triphosphate A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar (either ribose or deoxyribose), with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are chai ...
, which indicates that it consists of three components: a nitrogenous base (
adenine Adenine () (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. Th ...
), the sugar
ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−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 () (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. Th ...
attached by the 9-nitrogen atom to the 1′
carbon Carbon () is a chemical element with the chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—its atom making four electrons available to form covalent bond, covalent chemical bonds. It belongs to gro ...
atom Every atom is composed of a atomic nucleus, nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons. Every solid, l ...
of a sugar (
ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−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
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
and AMP. The three phosphoryl groups are labeled as alpha (α), beta (β), and, for the terminal phosphate, gamma (γ). In neutral solution, ionized ATP exists mostly as ATP4−, with a small proportion of ATP3−.

## Binding of metal cations to ATP

Being polyanionic and featuring a potentially chelating polyphosphate group, ATP binds metal cations with high affinity. The binding constant for is (). The binding of a
divalent In chemistry, the valence (US spelling) or valency (British spelling) of an chemical element, element is the measure of its combining capacity with other atoms when it forms chemical compounds or molecules. Description The combining capacity, ...
cation An ion () is an atom or molecule with a net electric charge, electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be po ...
, almost always
magnesium Magnesium is a chemical element with the Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group ...
, 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 to
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
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''.

# Reactive aspects

The hydrolysis of ATP into ADP and inorganic phosphate releases 20.5
kJ/mol The joule per mole (symbol: J·mol−1 or J/mol) is the unit of energy per amount of substance in the International System of Units (SI), such that energy is measured in joules, and the amount of substance is measured in mole (unit), moles. It ...
of
enthalpy Enthalpy , a property of a thermodynamic system, is the sum of the system's internal energy and the product of its pressure and volume. It is a state function used in many measurements in chemical, biological, and physical systems at a constant p ...
. The values of the free energy released by cleaving either a phosphate (Pi) or a pyrophosphate (PPi) unit from ATP at
standard state In chemistry, the standard state of a material (pure chemical substance, substance, mixture or Solution (chemistry), solution) is a reference point used to calculate its properties under different conditions. A superscript circle ° (degree symbo ...
concentrations of 1 mol/L at pH 7 are: :ATP + → ADP + Pi Δ''G''°' = −30.5 kJ/mol (−7.3 kcal/mol) :ATP + → AMP + PPi Δ''G''°' = −45.6 kJ/mol (−10.9 kcal/mol) These abbreviated equations at a pH near 7 can be written more explicitly (R = adenosyl): : O-P(O)2-O-P(O)2-O-PO3sup>4− + → O-P(O)2-O-PO3sup>3− + PO4sup>2− + H+ : O-P(O)2-O-P(O)2-O-PO3sup>4− + → O-PO3sup>2− + O3P-O-PO3sup>3− + H+ At cytoplasmic conditions, where the ADP/ATP ratio is 10 orders of magnitude from equilibrium, the Δ''G'' is around −57 kJ/mol.

# Production from AMP and ADP

## Production, aerobic conditions

A typical intracellular
concentration In chemistry, concentration is the Abundance (chemistry), abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: ''mass concentration (chemistry), mass concentration'', ...
of ATP is hard to pin down, however, reports have shown there to be 1–10 μmol 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 organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
s are (1)
glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate (). The Thermodynamic free energy, free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and NADH, red ...
, (2) the
citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the Redox, oxidation of acetyl-CoA derived from carbohydrates, fats, and p ...
/
oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order t ...
, and (3) beta-oxidation. The overall process of oxidizing glucose to
carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon Carbon () is a chemical element with the chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetraval ...
, the combination of pathways 1 and 2, known as
cellular respiration Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be des ...
, 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 Energy transformation, convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemica ...
aerobic eukaryote occurs mainly in the
mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which i ...
, 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 keto acids, alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate acid, conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throug ...
. Glycolysis generates two equivalents of ATP through substrate phosphorylation catalyzed by two enzymes, PGK and pyruvate kinase. 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 phosphat ...
are also produced, which can be oxidized via the
electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules that electron transfer, transfer electrons from electron donors to electron acceptors via redox reactions (both Redox#Definitions, reduction and oxidation occu ...
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 o ...
. The pyruvate generated as an end-product of glycolysis is a substrate for the Krebs Cycle. 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 that phosphorylation, phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate (biochemistry), substrate for hexokinases, and glucose-6-phospha ...
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 Phosphofructokinase (PFK) is a kinase enzyme that phosphorylation, phosphorylates fructose 6-phosphate in glycolysis. Function The enzyme-catalysed transfer of a phosphoryl group from Adenosine triphosphate, ATP is an important reaction in a ...
(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 that exists in two conformations, only one of which binds the second substrate fructose-6-phosphate (F6P). The protein has two
binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalent bond ...
s for ATP – the
active site In biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of Cell (biology), ce ...
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 is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary amm ...
ions, inorganic phosphate, and fructose-1,6- and -2,6-biphosphate.

### Citric acid cycle

In the
mitochondrion A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, 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 thi ...
to the
acetyl In organic chemistry, acetyl is a functional group with the chemical formula and the Chemical structure, structure . It is Skeletal formula#Pseudoelement symbols, sometimes represented by the symbol Ac (not to be confused with the element ac ...
group, which is fully oxidized to
carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon Carbon () is a chemical element with the chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetraval ...
by the
citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the Redox, oxidation of acetyl-CoA derived from carbohydrates, fats, and p ...
(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 nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription (genetics), transcription process. Its structure is similar to that of the guanosine ...
(GTP) through
substrate-level phosphorylation Substrate-level phosphorylation is a metabolism reaction that results in the production of Adenosine triphosphate, ATP or Guanosine triphosphate, GTP by the transfer of a phosphate group from a substrate directly to Adenosine diphosphate, ADP or ...
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 phosphat ...
oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order t ...
, generating additional ATP. The oxidation of NADH results in the synthesis of 2–3 equivalents of ATP, and the oxidation of one FADH2 yields between 1–2 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 with the chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen Group (periodic table), group in the periodic table, a highly Chemical reaction, reactive nonmetal, and an oxidizing a ...
, 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 ...
process because O2 is used to recycle the NADH and FADH2. 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 (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 with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes ...
to
malate Malic acid is an organic compound with the molecular formula . It is a dicarboxylic acid that is made by all living organisms, contributes to the sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms (L ...
, 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 enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...
converts the oxaloacetate to
aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
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 energy to pump
proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...
s out of the mitochondrial matrix and into the intermembrane space. This pumping generates a
proton motive force Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An important example is the formation of adenosine triphosphate, adenosine triphosphate (ATP) by the movement of hydrogen ion ...
that is the net effect of a pH 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 (physics), work energy needed to move a unit of electric charge from a reference point to the sp ...
gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient – that is, from the intermembrane space to the matrix – 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 o ...
. Three ATP are produced per turn. Although oxygen consumption appears fundamental for the maintenance of the
proton motive force Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An important example is the formation of adenosine triphosphate, adenosine triphosphate (ATP) by the movement of hydrogen ion ...
, 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 cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membr ...
, the
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
/ATP translocase, which is an
integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane protein, ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. ...
used to exchange newly synthesized ATP in the matrix for
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
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 30–38 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 A chemical element is a species of atoms that have a given number of protons in their atomic nucleus, nuclei, including the pure Chemical substance, substance consisting only of that species. Unlike chemica ...
, inorganic phosphate, ATP,
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
, and AMP.
Citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a Transparency and translucency, colorless Weak acid, weak organic acid. It occurs naturally in Citrus, citrus fruits. In biochemistry, it is an intermedi ...
– the ion that gives its name to the cycle – 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.

### 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 reactions in protein, carbohydrate and lipid metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining che ...
. 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 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 cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the Cellular respirati ...
, which is regulated by the availability of its substrate – the reduced form of cytochrome c. The amount of reduced cytochrome c available is directly related to the amounts of other substrates: :$\frac12 \ce + \ce\ \ce + \ce + \ce \rightleftharpoons \frac12 \ce + \ce\ \ce + \ce$ which directly implies this equation: :$\frac = \left\left(\frac\right\right)^\left\left(\frac\right\right)K_\mathrm$ Thus, a high ratio of ADHto AD+or a high ratio of DPPi] to TPimply 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 a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
to other tissues, where
acetoacetate Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound with the formula CH3COCH2COOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite st ...
and ''beta''-hydroxybutyrate can be reconverted to
acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining che ...
citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the Redox, oxidation of acetyl-CoA derived from carbohydrates, fats, and p ...
. Ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme β-ketoacyl-CoA transferase, also called
thiolase Thiolases, also known as acetyl-coenzyme A acetyltransferases (ACAT), are enzymes which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. Thiolases are ubiquitous enzymes that have key roles in many vital biochemi ...
.
Acetoacetate Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound with the formula CH3COCH2COOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite st ...
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 with the formula CH3COCH2COOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite st ...
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 metabolism, metabolic process that produces chemical changes in organic Substrate (chemistry), substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in ...
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 Adenosine triphosphate, ATP or Guanosine triphosphate, GTP by the transfer of a phosphate group from a substrate directly to Adenosine diphosphate, ADP or ...
in the absence of a respiratory
electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules that electron transfer, transfer electrons from electron donors to electron acceptors via redox reactions (both Redox#Definitions, reduction and oxidation occu ...
. The equation for the reaction of glucose to form
lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscibility, miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as ...
is: : + 2 ADP + 2 Pi → 2  + 2 ATP + 2  Anaerobic respiration is respiration in the absence of . 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 kinases (NDKs), which use other nucleoside triphosphates as a high-energy phosphate donor, and the ATP:guanido phosphotransferase family, 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 0.1 Molar concentration, mol/L. The majority of ATP is recycled from
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
by the aforementioned processes. Thus, at any given time, the total amount of ATP +
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Airpor ...
remains fairly constant. The energy used by human cells in an adult requires the hydrolysis of 100 to 150 mol/L of ATP daily, which means a human will typically use their body weight worth of ATP over the course of the day. Each equivalent of ATP is recycled 1000–1500 times during a single day (), at approximately 9×1020 molecules/s.

# 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 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. 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 ⟶ aa-AMP + pyrophosphate, PPi # 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 transporters. The human genome encodes 48 ABC transporters, that are used for exporting drugs, lipids, and other compounds.

## 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 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 hydrotrope 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 In biochemistry and molecular biology, a binding site is a region on a macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalent bond ...
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 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.

# 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, and he was awarded the Nobel Prize in Chemistry in 1957 partly for this work. The 1978 Nobel Prize in Chemistry was awarded to Dr. Peter D. Mitchell, Peter Dennis Mitchell for the discovery of the Chemiosmosis, chemiosmotic mechanism of ATP synthesis. 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."

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 o ...
* Citric acid cycle (also called the Krebs cycle or TCA cycle) * Creatine * Cyclic adenosine monophosphate (cAMP) * Nucleotide exchange factor * Phosphagen * Photophosphorylation

# References

ATP bound to proteins
in the Protein Data Bank, PDB
ScienceAid: Energy ATP and Exercise