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Adenosine triphosphate

Adenosine triphosphate

Overview
Adenosine-5'-triphosphate (ATP) is a multifunctional nucleoside triphosphate
Nucleoside triphosphate
Nucleoside triphosphate is a nucleoside with three phosphates. Natural nucleoside triphosphates include adenosine triphosphate , guanosine triphosphate , cytidine triphosphate , 5-methyluridine triphosphate , and uridine triphosphate . These terms refer to those nucleoside triphosphates that...

 used in cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 as a coenzyme. It is often called the "molecular
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

 unit of currency
Currency
In economics, currency refers to a generally accepted medium of exchange. These are usually the coins and banknotes of a particular government, which comprise the physical aspects of a nation's money supply...

" of intracellular energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

 transfer. ATP transports chemical energy within cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 for metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

. It is produced by photophosphorylation
Photophosphorylation
The production of ATP using the energy of sunlight is called photophosphorylation. Only two sources of energy are available to living organisms: sunlight and reduction-oxidation reactions...

 and cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

 and used by enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s and structural proteins
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

 in many cellular processes, including biosynthetic reactions
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

, motility, and cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

. One molecule of ATP contains three phosphate groups, and it is produced by ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...

 from inorganic phosphate and adenosine diphosphate
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 (ADP) or adenosine monophosphate
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

 (AMP).

Metabolic processes that use ATP as an energy source convert it back into its precursors.
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Encyclopedia
Adenosine-5'-triphosphate (ATP) is a multifunctional nucleoside triphosphate
Nucleoside triphosphate
Nucleoside triphosphate is a nucleoside with three phosphates. Natural nucleoside triphosphates include adenosine triphosphate , guanosine triphosphate , cytidine triphosphate , 5-methyluridine triphosphate , and uridine triphosphate . These terms refer to those nucleoside triphosphates that...

 used in cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 as a coenzyme. It is often called the "molecular
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

 unit of currency
Currency
In economics, currency refers to a generally accepted medium of exchange. These are usually the coins and banknotes of a particular government, which comprise the physical aspects of a nation's money supply...

" of intracellular energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

 transfer. ATP transports chemical energy within cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 for metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

. It is produced by photophosphorylation
Photophosphorylation
The production of ATP using the energy of sunlight is called photophosphorylation. Only two sources of energy are available to living organisms: sunlight and reduction-oxidation reactions...

 and cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

 and used by enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s and structural proteins
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

 in many cellular processes, including biosynthetic reactions
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

, motility, and cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

. One molecule of ATP contains three phosphate groups, and it is produced by ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...

 from inorganic phosphate and adenosine diphosphate
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 (ADP) or adenosine monophosphate
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

 (AMP).

Metabolic processes that use ATP as an energy source convert it back into its precursors. ATP is therefore continuously recycled in organisms: the human body, which on average contains only 250 grams (8.8 oz) of ATP, turns over its own body weight in ATP each day.

ATP is used as a substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 in signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 pathways by kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...

s that phosphorylate
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s and lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

s, as well as by adenylate cyclase
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

, which uses ATP to produce the second messenger molecule cyclic AMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...

. The ratio between ATP and AMP is used as a way for a cell to sense how much energy is available and control the metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

s that produce and consume ATP. Apart from its roles in energy metabolism and signaling, ATP is also incorporated into nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

s by polymerase
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...

s in the processes of DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 and transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

.

The structure of this molecule consists of a purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 base (adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...

) attached to the 1' carbon atom of a pentose
Pentose
A pentose is a monosaccharide with five carbon atoms. Pentoses are organized into two groups. Aldopentoses have an aldehyde functional group at position 1...

 sugar (ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

). Three phosphate groups are attached at the 5' carbon atom of the pentose sugar. It is the addition and removal of these phosphate groups that inter-convert ATP, ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 and AMP. When ATP is used in DNA synthesis, the ribose sugar is first converted to deoxyribose
Deoxyribose
Deoxyribose, more, precisely 2-deoxyribose, is a monosaccharide with idealized formula H---3-H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom...

 by ribonucleotide reductase
Ribonucleotide reductase
Ribonucleotide reductase is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms...

.

ATP was discovered in 1929 by Karl Lohmann, but its correct structure was not determined until some years later. It was proposed to be the main energy-transfer molecule in the cell by Fritz Albert Lipmann
Fritz Albert Lipmann
Fritz Albert Lipmann FRS was a German-American biochemist and a co-discoverer in 1945 of coenzyme A. For this, together with other research on coenzyme A, he was awarded half the Nobel Prize in Physiology or Medicine in 1953 .Lipmann was born in Königsberg, Germany to a Jewish family.Lipmann...

 in 1941. It was first artificially synthesized by Alexander Todd
Alexander R. Todd, Baron Todd
Alexander Robertus Todd, Baron Todd, OM, PRS FRSE was a Scottish biochemist whose research on the structure and synthesis of nucleotides, nucleosides, and nucleotide coenzymes gained him the 1957 Nobel Prize for Chemistry.Todd was born near Glasgow, attended Allan Glen's School and graduated from...

 in 1948.

Physical and chemical properties


ATP consists of adenosine — composed of an adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...

 ring and a ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

 sugar — and three phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

 groups (triphosphate). The phosphoryl groups, starting with the group closest to the ribose, are referred to as the alpha (α), beta (β), and gamma (γ) phosphates. Consequently, as a nucleotide, it (and its relatives ADP and AMP) is basically a monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...

 of RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

. ATP is highly soluble in water and is quite stable in solutions between pH 6.8–7.4, but is rapidly hydrolysed
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 at extreme pH. Consequently, ATP is best stored as an anhydrous salt.

ATP is an unstable molecule in unbuffered
Buffer solution
A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. It has the property that the pH of the solution changes very little when a small amount of strong acid or base is added to it. Buffer solutions are used as a...

 water, in which it hydrolyses to ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 and phosphate. This is because the strength of the bonds between the phosphate groups in ATP are less than the strength of the hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...

s (hydration bonds), between its products (ADP + phosphate), and water. Thus, if ATP and ADP are in chemical equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...

 in water, almost all of the ATP will eventually be converted to ADP. A system that is far from equilibrium contains Gibbs free energy
Gibbs free energy
In thermodynamics, the Gibbs free energy is a thermodynamic potential that measures the "useful" or process-initiating work obtainable from a thermodynamic system at a constant temperature and pressure...

, and is capable of doing work
Work (thermodynamics)
In thermodynamics, work performed by a system is the energy transferred to another system that is measured by the external generalized mechanical constraints on the system. As such, thermodynamic work is a generalization of the concept of mechanical work in mechanics. Thermodynamic work encompasses...

. Living cells maintain the ratio of ATP to ADP at a point ten orders of magnitude from equilibrium, with ATP concentrations a thousandfold higher than the concentration of ADP. This displacement from equilibrium means that the hydrolysis of ATP in the cell releases a large amount of free energy.

Two high-energy phosphate bonds (phosphoanhydride bonds) (those that connect adjacent phosphates) in an ATP molecule are responsible for the high energy content of this molecule. In the context of biochemical reactions, these anhydride bonds are frequently—and sometimes controversially—referred to as high-energy bonds. Energy stored in ATP may be released upon hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of the anhydride bonds. The bonds formed after hydrolysis—or the phosphorylation of a residue by ATP—are lower in energy than the phosphoanhydride bonds of ATP. During enzyme-catalyzed hydrolysis of ATP or phosphorylation by ATP, the available free energy can be harnessed by a living system to do work.

Any unstable system of potentially reactive molecules could potentially serve as a way of storing free energy, if the cell maintained their concentration far from the equilibrium point of the reaction. However, as is the case with most polymeric biomolecules, the breakdown of RNA, DNA, and ATP into simpler monomers is driven by both energy-release and entropy-increase considerations, in both standard concentrations, and also those concentrations encountered within the cell.

The standard amount of energy released from hydrolysis of ATP can be calculated from the changes in energy under non-natural (standard) conditions, then correcting to biological concentrations. The net change in heat energy (enthalpy
Enthalpy
Enthalpy is a measure of the total energy of a thermodynamic system. It includes the internal energy, which is the energy required to create a system, and the amount of energy required to make room for it by displacing its environment and establishing its volume and pressure.Enthalpy is a...

) at standard temperature and pressure
Standard conditions for temperature and pressure
Standard condition for temperature and pressure are standard sets of conditions for experimental measurements established to allow comparisons to be made between different sets of data...

 of the decomposition of ATP into hydrated ADP and hydrated inorganic phosphate is −20.5 kJ/mol
Joule per mole
The joule per mole is an SI derived unit of energy per amount of material. Energy is measured in joules, and the amount of material is measured in moles....

, with a change in free energy
Thermodynamic free energy
The thermodynamic free energy is the amount of work that a thermodynamic system can perform. The concept is useful in the thermodynamics of chemical or thermal processes in engineering and science. The free energy is the internal energy of a system less the amount of energy that cannot be used to...

 of 3.4 kJ/mol. The energy released by cleaving either a phosphate (Pi) or pyrophosphate (PPi) unit from ATP at standard state
Standard state
In chemistry, the standard state of a material is a reference point used to calculate its properties under different conditions. In principle, the choice of standard state is arbitrary, although the International Union of Pure and Applied Chemistry recommends a conventional set of standard states...

 of 1 M are:
ATP + H2O → ADP + Pi ΔG˚ = −30.5 kJ/mol (−7.3 kcal/mol)
ATP + H2O → AMP + PPi ΔG˚ = −45.6 kJ/mol (−10.9 kcal/mol)


These values can be used to calculate the change in energy under physiological conditions and the cellular ATP/ADP ratio. However, a more representative value (which takes AMP into consideration) called the Energy charge
Energy charge
Energy charge is an index used to measure the energy status of biological cells. It is related to ATP and ADP concentrations and its value effects rates of metabolism.From Stryer:"Many reactions in metabolism are controlled by the energy status of the cell...

 is increasingly being employed. The values given for the Gibbs free energy
Gibbs free energy
In thermodynamics, the Gibbs free energy is a thermodynamic potential that measures the "useful" or process-initiating work obtainable from a thermodynamic system at a constant temperature and pressure...

 for this reaction are dependent on a number of factors, including overall ionic strength and the presence of alkaline earth metal
Alkaline earth metal
The alkaline earth metals are a group in the periodic table. In the modern IUPAC nomenclature, the alkaline earth metals are called the group 2 elements. Previously, they were called the Group IIA elements . The alkaline earth metals contain beryllium , magnesium , calcium , strontium , barium and...

 ions such as Mg2+ and Ca2+. Under typical cellular conditions, ΔG is approximately −57 kJ/mol (−14 kcal/mol).

Ionization in biological systems


ATP has multiple ionizable groups with different acid dissociation constant
Acid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions...

s. In neutral solution, ATP is ionized and exists mostly as ATP4−, with a small proportion of ATP3−. As ATP has several negatively charged groups in neutral solution, it can chelate
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....

 metals with very high affinity. The binding constant for various metal ions are (given as per mole) as Mg2+
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

 (9 554), Na+
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 (13), Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 (3 722), K+
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 (8), Sr2+
Strontium
Strontium is a chemical element with the symbol Sr and the atomic number 38. An alkaline earth metal, strontium is a soft silver-white or yellowish metallic element that is highly reactive chemically. The metal turns yellow when exposed to air. It occurs naturally in the minerals celestine and...

 (1 381) and Li+
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...

 (25). Due to the strength of these interactions, ATP exists in the cell mostly in a complex with Mg2+.

Biosynthesis


The ATP concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

 inside the cell is typically 1–10 mM. ATP can be produced by redox
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 reactions using simple and complex sugars (carbohydrates) or lipids as an energy source. For ATP to be synthesized from complex fuels, they first need to be broken down into smaller, more simple molecules. Carbohydrates are hydrolysed
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 into simple sugars, such as glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 and fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

. Fats (triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....

s) are metabolised to give fatty acids and glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...

.

The overall process of oxidizing glucose to carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

 is known as cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

 and can produce about 30 molecules of ATP from a single molecule of glucose. ATP can be produced by a number of distinct cellular processes; the three main pathways used to generate energy in eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 organisms are glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...

 and the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

/oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

, both components of cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

; and beta-oxidation. The majority of this ATP production by a non-photosynthetic aerobic eukaryote takes place in the mitochondria, which can make up nearly 25% of the total volume of a typical cell.

Glycolysis


In glycolysis, glucose and glycerol are metabolized to pyruvate via the glycolytic pathway. In most organisms, this process occurs in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

, but, in some protozoa such as the kinetoplastid
Kinetoplastid
The kinetoplastids are a group of single-cell flagellate protozoa, including a number of parasites responsible for serious diseases in humans and other animals, as well as various forms found in soil and aquatic environments...

s, this is carried out in a specialized organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....

 called the glycosome
Glycosome
The glycosome is a membrane-enclosed organelle that contains the glycolytic enzymes. It is found in a few species of protozoa, most notably in the human pathogenic trypanosomes, which can cause sleeping sickness and Chagas's disease, and Leishmania. The organelle is bounded by a single membrane and...

. Glycolysis generates a net two molecules of ATP through substrate phosphorylation
Substrate-level phosphorylation
Substrate-level phosphorylation is a type of metabolism that results in the formation and creation of adenosine triphosphate or guanosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate or guanosine diphosphate from a phosphorylated reactive...

 catalyzed by two enzymes: PGK
Phosphoglycerate kinase
Phosphoglycerate kinase is a transferase enzyme used in the seventh step of glycolysis. It transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-Phosphoglycerate....

 and pyruvate kinase
Pyruvate kinase
Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:...

. Two molecules of NADH are also produced, which can be oxidized via the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...

 and result in the generation of additional ATP by ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...

. The pyruvate generated as an end-product of glycolysis is a substrate for the Krebs Cycle.

Glucose


In the mitochondrion
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...

, pyruvate is oxidized by the pyruvate dehydrogenase complex to Acetyl group, which is fully oxidized to carbon dioxide by the citric acid cycle (also known as the Krebs Cycle). Every "turn" of the citric acid cycle produces two molecules of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

, one molecule of the ATP equivalent guanosine triphosphate
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 (GTP) through substrate-level phosphorylation
Substrate-level phosphorylation
Substrate-level phosphorylation is a type of metabolism that results in the formation and creation of adenosine triphosphate or guanosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate or guanosine diphosphate from a phosphorylated reactive...

 catalyzed by succinyl-CoA synthetase, three molecules of the reduced coenzyme NADH, and one molecule of the reduced coenzyme FADH2. Both of these latter molecules are recycled to their oxidized states (NAD+ and FAD
FAD
In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...

, respectively) via the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...

, which generates additional ATP by oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

. The oxidation of an NADH molecule results in the synthesis of between 2-3 ATP molecules, and the oxidation of one FADH2 yields between 1-2 ATP molecules. The majority of cellular ATP is generated by this process. Although the citric acid cycle itself does not involve molecular oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

, it is an obligately aerobic process because O2 is needed to recycle the reduced NADH and FADH2 to their oxidized states. In the absence of oxygen the citric acid cycle will cease to function due to the lack of available NAD+ and FAD.

The generation of ATP by the mitochondrion from cytosolic NADH relies on the malate-aspartate shuttle
Malate-aspartate shuttle
The malate-aspartate shuttle is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes. These electrons enter the electron transport chain of the mitochondria via reduction...

 (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
Malate dehydrogenase
Malate dehydrogenase is an enzyme in the citric acid cycle that catalyzes the conversion of malate into oxaloacetate and vice versa...

 enzyme converts oxaloacetate to malate
Malate
Malate is the ionized form of malic acid. It is an important chemical compound in biochemistry. In the C4 carbon fixation process, malate is a source of CO2 in the Calvin cycle....

, 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
Transaminase
In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. To be specific, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to the...

 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 powers the pumping of proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....

s out of the mitochondrial matrix and into the intermembrane space. This creates a proton motive force that is the net effect of a pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

 gradient and an electric potential
Electric potential
In classical electromagnetism, the electric potential at a point within a defined space is equal to the electric potential energy at that location divided by the charge there...

 gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient — that is, from the intermembrane space to the matrix — provides the driving force for ATP synthesis by ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...

. This enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 contains a rotor subunit that physically rotates relative to the static portions of the protein during 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. The inner membrane contains an antiporter
Antiporter
An antiporter is an integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions.In secondary active transport, one species of solute moves along its electrochemical...

, the ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

/ATP translocase, which is an integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...

 used to exchange newly-synthesized ATP in the matrix for ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 in the intermembrane space. This translocase is driven by the membrane potential, as it results in the movement of about 4 negative charges out of 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.

Beta oxidation


Fatty acids can also be broken down to acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

 by beta-oxidation. Each round of this cycle reduces the length of the acyl chain by two carbon atoms and produces one NADH and one FADH2 molecule, which are used to generate ATP by oxidative phosphorylation. Because NADH and FADH2 are energy-rich molecules, dozens of ATP molecules can be generated by the beta-oxidation of a single long acyl chain. The high energy yield of this process and the compact storage of fat explain why it is the most dense source of dietary calorie
Calorie
The calorie is a pre-SI metric unit of energy. It was first defined by Nicolas Clément in 1824 as a unit of heat, entering French and English dictionaries between 1841 and 1867. In most fields its use is archaic, having been replaced by the SI unit of energy, the joule...

s.

Anaerobic respiration


Anaerobic respiration or fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

 entails the generation of energy via the process of oxidation in the absence of O2
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 as an electron acceptor
Electron acceptor
An electron acceptor is a chemical entity that accepts electrons transferred to it from another compound. It is an oxidizing agent that, by virtue of its accepting electrons, is itself reduced in the process....

. In most eukaryotes, glucose is used as both an energy store and an electron donor. The equation for the oxidation of glucose to lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

 is:
C6H12O6 2CH3CH(OH)COOH + 2 ATP


In prokaryotes, multiple electron acceptors can be used in anaerobic respiration. These include nitrate
Nitrate
The nitrate ion is a polyatomic ion with the molecular formula NO and a molecular mass of 62.0049 g/mol. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identically-bonded oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a...

, sulfate
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...

 or carbon dioxide. These processes lead to the ecologically-important processes of denitrification
Denitrification
Denitrification is a microbially facilitated process of nitrate reduction that may ultimately produce molecular nitrogen through a series of intermediate gaseous nitrogen oxide products....

, sulfate reduction and acetogenesis
Acetogenesis
Acetogenesis is a process through which acetate is produced by anaerobic bacteria from a variety of energy and carbon sources. The different bacterial species that are capable of acetogenesis are collectively termed acetogens.-Biochemistry:The precursor to acetic acid is the thioester acetyl CoA...

, respectively.

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
ATP:guanido phosphotransferase family
In molecular biology, the ATP:guanido phosphotransferase family is a family of structurally and functionally related enzymes, that reversibly catalyse the transfer of phosphate between ATP and various phosphogens...

 family,

ATP production during photosynthesis


In plants, ATP is synthesized in thylakoid membrane of the chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...

 during the light-dependent reactions of photosynthesis
Photosynthesis
Photosynthesis is a chemical process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of bacteria, but not in archaea. Photosynthetic organisms are called photoautotrophs, since they can...

 in a process called photophosphorylation. Here, light energy is used to pump protons across the chloroplast membrane. This produces a proton-motive force and this drives the ATP synthase, exactly as in oxidative phosphorylation. Some of the ATP produced in the chloroplasts is consumed in the Calvin cycle
Calvin cycle
The Calvin cycle or Calvin–Benson-Bassham cycle or reductive pentose phosphate cycle or C3 cycle or CBB cycle is a series of biochemical redox reactions that take place in the stroma of chloroplasts in photosynthetic organisms...

, which produces triose
Triose
A triose is a monosaccharide, or simple sugar, containing three carbon atoms. There are only three possible trioses: L-Glyceraldehyde and D-Glyceraldehyde, both aldotrioses because the carbonyl group is at the end of the chain, and dihydroxyacetone, a ketotriose because the carbonyl group is in...

 sugars.

ATP recycling


The total quantity of ATP in the human body is about 0.1 mole
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...

. The majority of ATP is not usually synthesised de novo, but is generated from ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 by the aforementioned processes. Thus, at any given time, the total amount of ATP + ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 remains fairly constant.

The energy used by human cells requires the hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of 100 to 150 moles of ATP daily, which is around 50 to 75 kg. A human will typically use up his or her body weight of ATP over the course of the day. This means that each ATP molecule is recycled 1000 to 1500 times during a single day (100 / 0.1 = 1000). ATP cannot be stored, hence its consumption closely follows its synthesis.

Regulation of biosynthesis


ATP production in an aerobic eukaryotic cell is tightly regulated by allosteric mechanisms, by feedback
Feedback
Feedback describes the situation when output from an event or phenomenon in the past will influence an occurrence or occurrences of the same Feedback describes the situation when output from (or information about the result of) an event or phenomenon in the past will influence an occurrence or...

 effects, and by the substrate concentration dependence of individual enzymes within the glycolysis and oxidative phosphorylation pathways. Key control points occur in enzymatic reactions that are so energetically favorable that they are effectively irreversible under physiological conditions.

In glycolysis, hexokinase
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....

 is directly inhibited by its product, glucose-6-phosphate, and pyruvate kinase
Pyruvate kinase
Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:...

 is inhibited by ATP itself. The main control point for the glycolytic pathway is phosphofructokinase
Phosphofructokinase
Phosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors...

 (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 biologically active form of the enzyme is a tetramer that exists in two possible conformations, only one of which binds the second substrate fructose-6-phosphate (F6P). The protein has two binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...

s for ATP - the active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

 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, ammonium
Ammonium
The ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...

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

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
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

, inorganic phosphate, ATP, ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

, and AMP. Citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...

 - the molecule that gives its name to the cycle - is a feedback inhibitor of citrate synthase
Citrate synthase
The enzyme citrate synthase exists in nearly all living cells and stands as a pace-making enzyme in the first step of the Citric Acid Cycle . Citrate synthase is localized within eukaryotic cells in the mitochondrial matrix, but is encoded by nuclear DNA rather than mitochondrial...

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

In oxidative phosphorylation, the key control point is the reaction catalyzed by cytochrome c oxidase
Cytochrome c oxidase
The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...

, which is regulated by the availability of its substrate—the reduced form of cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...

. The amount of reduced cytochrome c available is directly related to the amounts of other substrates:
which directly implies this equation:

Thus, a high ratio of [NADH] to [NAD+] or a low ratio of [ADP] [Pi] to [ATP] 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.

Metabolism, synthesis, and active transport


ATP is consumed in the cell by energy-requiring (endothermic) processes and can be generated by energy-releasing (exothermic) processes. In this way ATP transfers energy between spatially-separate metabolic reactions
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

. ATP is the main energy source for the majority of cellular functions. This includes the synthesis of macromolecules, including DNA
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 and RNA
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

 (see below), and proteins
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

. ATP also plays a critical role in the transport
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...

 of macromolecules across cell membranes, e.g. exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

 and endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

.

Roles in cell structure and locomotion


ATP is critically involved in maintaining cell structure by facilitating assembly and disassembly of elements of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

. In a related process, ATP is required for the shortening of actin and myosin filament crossbridges
Sliding filament mechanism
The sliding filament theory describes a process used by muscles to contract. It was independently developed by Andrew F. Huxley and Rolf Niedergerke and by Hugh Huxley and Jean Hanson in 1954.-Process of movement:...

 required for muscle contraction
Muscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...

. This latter process is one of the main energy requirements of animals and is essential for locomotion
Animal locomotion
Animal locomotion, which is the act of self-propulsion by an animal, has many manifestations, including running, swimming, jumping and flying. Animals move for a variety of reasons, such as to find food, a mate, or a suitable microhabitat, and to escape predators...

 and respiration
Respiratory system
The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...

.

Extracellular signalling


ATP is also a signalling molecule. ATP, ADP, or adenosine are recognised by purinergic receptors. Purinoreceptors might be the most abundant receptors in mammalian tissues (Abbracchio M.P. et al., 2008).

In humans, this signalling role is important in both the central and peripheral nervous system. Activity-dependent release of ATP from synapses, axons and glia activates purinergic membrane receptors known as P2. The P2Y receptors are metabotropic, i.e. G protein-coupled
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 and modulate mainly intracellular calcium and sometimes cyclic AMP levels. Though named between P2Y1 and P2Y15, only nine members of the P2Y family have been cloned, and some are only related through weak homology and several (P2Y5, P2Y7, P2Y9, P2Y10) do not function as receptors that raise cytosolic calcium. The P2X ionotropic receptor subgroup comprises seven members (P2X1–P2X7), which are ligand-gated Ca2+-permeable ion channels that open when bound to an extracellular purine nucleotide. In contrast to P2 receptors (agonist order ATP > ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 > AMP > ADO), purinergic nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

s like ATP are not strong agonists of P1 receptors, which are strongly activated by adenosine and other nucleoside
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...

s (ADO > AMP > ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 > ATP). P1 receptors have A1, A2a, A2b, and A3 subtypes ("A" as a remnant of old nomenclature of adenosine receptor), all of which are G protein-coupled receptors, A1 and A3 being coupled to Gi, and A2a and A2b being coupled to Gs.

All adenosine receptors were shown to activate at least one subfamily of mitogen-activated protein kinases. The actions of adenosine are often antagonistic or synergistic to the actions of ATP. In the CNS, adenosine has multiple functions, such as modulation of neural development, neuron and glial signalling and the control of innate and adaptive immune systems (Abbracchio M.P. et al., 2008).

Intracellular signalling


ATP is critical in signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 processes. It is used by kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...

s as the source of phosphate groups in their phosphate transfer reactions. Kinase activity on substrates such as proteins or membrane lipids are a common form of signal transduction. Phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 of a protein by a kinase can activate this cascade such as the mitogen-activated protein kinase
Mitogen-activated protein kinase
Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...

 cascade.

ATP is also used by adenylate cyclase
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

 and is transformed to the second messenger molecule 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


In all known organisms, the deoxyribonucleotides that make up DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 are synthesized by the action of ribonucleotide reductase
Ribonucleotide reductase
Ribonucleotide reductase is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms...

 (RNR) enzymes on their corresponding ribonucleotides. These enzymes reduce the sugar residue from ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

 to deoxyribose
Deoxyribose
Deoxyribose, more, precisely 2-deoxyribose, is a monosaccharide with idealized formula H---3-H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom...

 by removing oxygen from the 2' hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

 group; the substrates are ribonucleoside diphosphates and the products deoxyribonucleoside diphosphates (the latter are denoted dADP, dCDP, dGDP, and dUDP respectively.) All ribonucleotide reductase enzymes use a common sulfhydryl radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...

 mechanism reliant on reactive cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 residues that oxidize to form disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...

s in the course of the reaction. RNR enzymes are recycled by reaction with thioredoxin
Thioredoxin
Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes. In humans, it is encoded by the TXN gene. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the...

 or glutaredoxin
Glutaredoxin
Glutaredoxins are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no...

.

The regulation of RNR and related enzymes maintains a balance of dNTPs relative to each other and relative to NTPs in the cell. Very low dNTP concentration inhibits DNA synthesis
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 and DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

 and is lethal to the cell, while an abnormal ratio of dNTPs is mutagen
Mutagen
In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...

ic due to the increased likelihood of the DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....

 incorporating the wrong dNTP during DNA synthesis. Regulation of or differential specificity of RNR has been proposed as a mechanism for alterations in the relative sizes of intracellular dNTP pools under cellular stress such as hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...

.

In the synthesis of the nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

 RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

, ATP is one of the four nucleotides incorporated directly into RNA molecules by RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

s. The energy driving this polymerization comes from cleaving off a pyrophosphate (two phosphate groups). The process is similar in DNA biosynthesis, except that ATP is reduced to the deoxyribonucleotide
Deoxyribonucleotide
A deoxyribonucleotide is the monomer, or single unit, of DNA, or deoxyribonucleic acid. Each deoxyribonucleotide comprises three parts: a nitrogenous base, a deoxyribose sugar, and one phosphate group. The nitrogenous base is always bonded to the 1' carbon of the deoxyribose, which is distinguished...

 dATP, before incorporation into DNA.

Binding to proteins



Some proteins that bind ATP do so in a characteristic protein fold
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 known as the Rossmann fold
Rossmann fold
The Rossmann fold is a protein structural motif found in proteins that bind nucleotides, especially the cofactor NAD. The structure with two repeats is composed of six parallel beta strands linked to two pairs of alpha helices in the topological order beta-alpha-beta-alpha-beta...

, which is a general nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

-binding structural domain that can also bind the coenzyme NAD
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...

. The most common ATP-binding proteins, known as kinases, share a small number of common folds; the protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...

s, the largest kinase superfamily, all share common structural features specialized for ATP binding and phosphate transfer.

ATP in complexes with proteins, in general, requires the presence of a divalent
Divalent
In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....

 cation, almost always magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

, which binds to the ATP phosphate groups. The presence of magnesium greatly decreases the dissociation constant
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...

 of ATP from its protein binding partner without affecting the ability of the enzyme to catalyze its reaction once the ATP has bound. The presence of magnesium ions can serve as a mechanism for kinase regulation.

ATP analogues


Biochemistry laboratories often use in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

studies to explore ATP-dependent molecular processes. Enzyme inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

s of ATP-dependent enzymes such as kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...

s are needed to examine the binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...

s and transition state
Transition state
The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules will always...

s involved in ATP-dependent reactions. ATP analogs are also used in X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

 to determine a protein structure
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...

 in complex with ATP, often together with other substrates.
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'-(gamma-thiotriphosphate) is an extremely common ATP analog in which one of the gamma-phosphate oxygens is replaced by a sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

 atom; this molecule 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
Vanadate
In chemistry, a vanadate is a compound containing an oxoanion of vanadium generally in its highest oxidation state of +5. The simplest vanadate ion is the tetrahedral, orthovanadate, VO43− anion, which is present in e.g. sodium orthovanadate and in solutions of V2O5 in strong base...

 ion. However, caution is warranted in interpreting the results of experiments using ATP analogs, since some enzymes can hydrolyze them at appreciable rates at high concentration.

See also

  • Adenosine diphosphate
    Adenosine diphosphate
    Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

     (ADP
    Adenosine diphosphate
    Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

    )
  • Adenosine monophosphate
    Adenosine monophosphate
    Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

     (AMP)
  • Cyclic adenosine monophosphate
    Cyclic adenosine monophosphate
    Cyclic adenosine monophosphate is a second messenger important in many biological processes...

     (cAMP)
  • ATPases
  • ATP Test
    ATP test
    The ATP test is a process of rapidly measuring actively growing microorganisms through detection of adenosine triphosphate, or ATP.-ATP testing method:...

  • ATP hydrolysis
    ATP hydrolysis
    ATP hydrolysis is the reaction by which chemical energy that has been stored and transported in the high-energy phosphoanhydridic bonds in ATP is released, for example in the muscles, to produce work. The product is ADP and an inorganic phosphate, orthophosphate...

  • Citric acid cycle
    Citric acid cycle
    The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

     (also called the Krebs cycle or TCA cycle)
  • Phosphagen
    Phosphagen
    The phosphagens are energy storage compounds, also known as high-energy phosphate compounds, are chiefly found in muscular tissue in animals. They allow a high-energy phosphate pool to be maintained in a concentration range, which, if it all were ATP, would create problems due to the ATP consuming...

  • Nucleotide exchange factor
    Nucleotide exchange factor
    Nucleotide exchange factors are proteins that stimulate the exchange of nucleoside diphosphates for nucleoside triphosphates bound to other proteins.-Function:...

  • Mitochondria
  • Photophosphorylation
    Photophosphorylation
    The production of ATP using the energy of sunlight is called photophosphorylation. Only two sources of energy are available to living organisms: sunlight and reduction-oxidation reactions...


External links