Adenosine-5'-triphosphate (
ATP) is a multifunctional
nucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism...
that plays an important role in
cell biologyCell biology is an academic discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
as a coenzyme, that is, the "
molecularA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
unit of
currencyIn economics, the term currency can refer either to a particular currency, for example the US dollar, or to the coins and banknotes of a particular currency, which comprise the physical aspects of a nation's money supply...
" of intracellular
energyIn physics, energy is a scalar physical quantity that describes the amount of work that can be performed by a force, an attribute of objects and systems that is subject to a conservation law...
transfer. ATP transports chemical energy within
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
for
metabolismMetabolism is the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter,...
. It is an energy source produced during
photosynthesisPhotosynthesis is a 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...
and
cellular respirationCellular respiration is one of the key ways a cell gains useful energy. It is the set of the metabolic reactions and processes that take place in organisms' cells to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products...
and consumed by many
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s and a multitude of cellular processes, including
biosynthetic reactionsBiosynthesis 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...
,
motilityMotility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. It can apply to either single-celled or multicellular organisms. Motile marine animals are commonly called free-swimming...
, and
cell divisionCell division is a process by which a cell, called the parent cell, divides into two or more cells, called 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...
. ATP is made from
adenosine diphosphateAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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 monophosphateAdenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is found in RNA. It is an ester of phosphoric acid and the nucleoside adenosine...
(AMP) and its use in metabolism converts it back into these precursors. ATP is therefore continuously recycled in organisms, with the human body turning over its own weight in ATP each day.
ATP is used as a
substrateIn 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 transductionIn biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers,...
pathways by
kinaseIn chemistry and biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates. The process is referred to as phosphorylation...
s that
phosphorylatePhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many protein enzymes on and off, causing or preventing the mechanisms of diseases such as cancer and diabetes....
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s and
lipidLipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others...
s, as well as by
adenylate cyclaseAdenylate cyclase is a lyase enzyme. It is a part of the cAMP-dependent pathway-Types:There are ten known adenylate cyclases in mammals:* ADCY1* ADCY2* ADCY3* ADCY4* ADCY5...
, which uses ATP to produce the second messenger molecule
cyclic AMPCyclic 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-Cellular respiration:Several distinct but linked metabolic pathways are used by cells to transfer the energy released by breakdown of fuel molecules to ATP...
s that produce and consume ATP. Apart from its roles in energy metabolism and signaling, ATP is also incorporated into
nucleic acidA nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acid . Nucleic acids are universal in living things, as...
s by
polymeraseA 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 replicationDNA replication, the basis for biological inheritance, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand...
and
transcriptionTranscription, or RNA synthesis, is the process of creating an equivalent 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 in the presence of the correct enzymes...
.
The structure of this molecule consists of a
purineA 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 (
adenineAdenine 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
pentoseA pentose is a monosaccharide with five carbon atoms.They either have an aldehyde functional group in position 1 , or a ketone functional group in position 2 ....
sugar (
riboseRibose, primarily occurring as
D-ribose, is an organic compound that occurs widely in nature. It is an aldopentose, that is a monosaccharide containing five carbon atoms that, in its acyclic form, has an aldehyde functional group at one end. This species predominantly exists in the...
). 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,
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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
deoxyriboseDeoxyribose, also known as
D-Deoxyribose and 2-deoxyribose, is an aldopentose — a monosaccharide containing five carbon atoms, and including an aldehyde functional group in its linear structure...
by
ribonucleotide reductaseRibonucleotide 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 LipmannFritz Albert Lipmann 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....
in 1941. It was first artificially synthesized by
Alexander ToddAlexander Todd may refer to the following people:* Alexander Todd , England and British Lions rugby union player* Alexander R. Todd, Baron Todd, Scottish biochemist and Nobel Prize winner...
in 1948.
Physical and chemical properties
ATP consists of
adenosineAdenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule moiety via a β-N
9-glycosidic bond....
— composed of an
adenineAdenine 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
riboseRibose, primarily occurring as
D-ribose, is an organic compound that occurs widely in nature. It is an aldopentose, that is a monosaccharide containing five carbon atoms that, in its acyclic form, has an aldehyde functional group at one end. This species predominantly exists in the...
sugar — and three
phosphateA 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. ATP is highly soluble in water and is quite stable in solutions between pH 6.8–7.4, but is rapidly
hydrolysedHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
at extreme pH. Consequently, ATP is best stored as an anhydrous salt.
ATP is an unstable molecule in
unbufferedA 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 acid or base is added to it. Buffer solutions are used as a means...
water, which hydrolyses to
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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 residues in ATP are less than the strength of the "hydration" bonds between its products (
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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....
+ phosphate), and water. Thus, if ATP and
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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....
are in
chemical equilibriumIn a chemical process, chemical equilibrium is the state in which the chemical activities or concentrations of the reactants and products have no net change over time. Usually, this would be the state that results when the forward chemical process proceeds at the same rate as their reverse reaction...
in water, almost all of the ATP will eventually be converted to
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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....
. A system that is far from equilibrium contains
Gibbs free energyIn thermodynamics, the Gibbs free energy is a thermodynamic potential that measures the "useful" or process-initiating work obtainable from an isothermal, isobaric thermodynamic system...
, and is capable of doing
workIn thermodynamics, work performed by a system is the quantity of energy transferred by the system to another due to changes in the external parameters of the system. If these changes happen in a reversible way, then the performed work does not lead to a change of the entropy. It is a...
. Living cells maintain the ratio of ATP to
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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....
at a point ten orders of magnitude from equilibrium, with ATP concentrations a thousandfold higher than the concentration of
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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....
. This displacement from equilibrium means that the hydrolysis of ATP in the cell releases a great amount of energy.
The energy content of an isolated molecule of ATP is a consequence of the anhydride bonds that connect adjacent phosphates. Anhydrides exhibit increased reactivity compared to their corresponding acids. This is because the bonds that constitute an anhydride moiety are less stable (hence higher in energy) than the bonds that can be formed from
nucleophilic substitutionIn organic and inorganic chemistry, nucleophilic substitution is a fundamental class of substitution reaction in which an "electron rich" nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom attached to a group or atom called the leaving group; the...
. In the case of ATP, the bonds formed from hydrolysis, or the phosphorylation of a residue by ATP, are lower in energy than the phosphoanhydride bonds of ATP. Upon enzyme-mediated hydrolysis of ATP or phosphorylation by ATP, this 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 (
enthalpyIn thermodynamics and molecular chemistry, the enthalpy is a thermodynamic property of a thermodynamic system. It can be used to calculate the heat transfer during a quasistatic process taking place in a closed thermodynamic system under constant pressure...
) at
standard temperature and pressureIn physical sciences, standard conditions for temperature and pressure are standard sets of conditions for experimental measurements, to allow comparisons to be made between different sets of data...
of the decomposition of ATP into hydrated
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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 hydrated inorganic phosphate is −20.5
kJ/molThe 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 energyIn thermodynamics, the term thermodynamic free energy refers to the amount of work that can be extracted from a system, and is helpful in engineering applications...
of 3.4 kJ/mol. The energy released by cleaving either a phosphate (P
i) or pyrophosphate (PP
i) unit from ATP at
standard stateIn 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/
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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....
ratio. The values given for the
Gibbs free energyIn thermodynamics, the Gibbs free energy is a thermodynamic potential that measures the "useful" or process-initiating work obtainable from an isothermal, isobaric thermodynamic system...
for this reaction are dependent on a number of factors, including overall ionic strength and the presence of
alkaline earth metalThe alkaline earth metals are a series of elements comprising Group 2 of the periodic table: beryllium , magnesium , calcium , strontium , barium and radium . This specific group in the periodic table owes its name to their oxides that simply give basic alkaline solutions...
ions such as Mg
2+ and Ca
2+. 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 constantAn 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 ATP
4−, with a small proportion of ATP
3−. As ATP has several negatively-charged groups in neutral solution, it can
chelateChelation is the formation or presence of two or more separate bindings between apolydentate ligand and a single central atom.Usually these ligands are organic compounds, and are called chelants, chelators, chelating agents, or sequestering agents....
metals with very high affinity. The
binding constantThe binding constant is a special case of the equilibrium constant K. The equilibrium state of molecular binding, i.e. the balance between the binding and dissociation processes after infinite reaction time, may be formalized as the unbound compounds transforming into a complex :This...
for various metal ions are (given as per mole) as
Mg2+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 by mass, although ninth in the Universe as a whole...
(9 554),
Na+Sodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
(13),
Ca2+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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
(3 722),
K+Potassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
(8),
Sr2+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 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 three. 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 Mg
2+.
Biosynthesis
The ATP
concentrationIn chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
inside the cell is typically 1–10 mM. ATP can be produced by
redoxRedox describes all chemical reactions in which atoms have their oxidation number 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 their basic components. Carbohydrates are
hydrolysedHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
into simple sugars, such as
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
and
fructoseFructose is a simple monosaccharide found in many foods. It is a white solid that dissolves readily in water. Honey, tree fruits, berries, melons, and some root vegetables, contain significant amounts of the fructose derivative sucrose...
. Fats (
triglycerideis a glyceride in which the glycerol is esterified with three fatty acids. It is the main constituent of vegetable oil and animal fats.- Chemical structure :...
s) are metabolised to give fatty acids and
glycerolGlycerol is an organic compound, also commonly called glycerin or glycerine. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydrophilic hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. ...
.
The overall process of oxidizing glucose to
carbon dioxideCarbon dioxide is a chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom. It is a gas at standard temperature and pressure and exists in Earth's atmosphere in this state...
is known as
cellular respirationCellular respiration is one of the key ways a cell gains useful energy. It is the set of the metabolic reactions and processes that take place in organisms' cells to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products...
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
eukaryoticA eukaryote is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried...
organisms are
glycolysisGlycolysis is the metabolic pathway that converts glucose, C
6H
12O
6, into pyruvate, C
3H
6O
3-...
and the
citric acid cycleThe citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or more rarely, the Szent-Györgyi-Krebs cycle — is a series of enzyme-catalysed chemical reactions, which is of central importance in all living cells that use oxygen as part of cellular respiration...
/
oxidative phosphorylationOxidative 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 carry out oxidative phosphorylation to produce ATP, the molecule that...
, both components of
cellular respirationCellular respiration is one of the key ways a cell gains useful energy. It is the set of the metabolic reactions and processes that take place in organisms' cells to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products...
; 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
cytosolThe cytosol or intracellular fluid is the liquid found inside cells. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion...
, but in some protozoa such as the
kinetoplastidThe kinetoplastids are a group of 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
organelleIn 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 membrane....
called the
glycosomeThe 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 phosphorylationSubstrate-level phosphorylation is a type of chemical reaction that results in the formation and creation of adenosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate from a reactive intermediate...
catalyzed by two enzymes:
PGK and
pyruvate kinasePyruvate 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 chainAn electron transport chain couples a chemical reaction between an electron donor and an electron acceptor to the transfer of H+ ions across a membrane, through a set of mediating biochemical reactions...
and result in the generation of additional ATP by
ATP synthaseAn ATP synthase is a general term for an enzyme that can synthesize adenosine triphosphate from adenosine diphosphate and inorganic phosphate by using some form of energy...
. The pyruvate generated as an end-product of glycolysis is a substrate for the Krebs Cycle.
Glucose
In the
mitochondrionIn cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5–10 micrometers in diameter...
, pyruvate is oxidized by the pyruvate dehydrogenase complex to acetyl CoA, 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 dioxideCarbon dioxide is a chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom. It is a gas at standard temperature and pressure and exists in Earth's atmosphere in this state...
, one molecule of the ATP equivalent
guanosine triphosphateGuanosine-5'-triphosphate is a purine nucleotide. It can act as a substrate for the synthesis of RNA during transcription process...
(GTP) through
substrate-level phosphorylationSubstrate-level phosphorylation is a type of chemical reaction that results in the formation and creation of adenosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate from a reactive intermediate...
catalyzed by succinyl CoA synthetase, three molecules of the reduced coenzyme NADH, and one molecule of the reduced coenzyme FADH
2. Both of these latter molecules are recycled to their oxidized states (NAD
+ and
FADIn biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states and its biochemical role usually involves changing between these two states...
, respectively) via the
electron transport chainAn electron transport chain couples a chemical reaction between an electron donor and an electron acceptor to the transfer of H+ ions across a membrane, through a set of mediating biochemical reactions...
, which generates additional ATP by
oxidative phosphorylationOxidative 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 carry out oxidative phosphorylation to produce ATP, the molecule that...
. The oxidation of an NADH molecule results in the synthesis of between 2-3 ATP molecules, and the oxidation of one FADH
2 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
oxygenOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
, it is an obligately aerobic process because O
2 is needed to recycle the reduced NADH and FADH
2 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 shuttleThe malate-aspartate shuttle is a biochemical system for translocating electrons produced during glycolysis across the impermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes...
(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 dehydrogenaseMalate 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, 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
transaminaseIn biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. Specifically, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to...
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 FADH
2 through the electron transport chain powers the pumping of
protonThe proton is a subatomic particle with an electric charge of +1 elementary charge. It is found in the nucleus of each atom but is also stable by itself and has a second identity as the hydrogen ion, H
+...
s out of the mitochondrial matrix and into the intermembrane space. This creates a proton motive force that is the net effect of a
pHpH is a measure of the acidity or basicity of a solution. It is defined as the cologarithm of the activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations...
gradient and an
electric potentialAt a point in space, the electric potential is potential energy divided by charge that is associated with a static electric field. It is a scalar quantity, typically measured in volts....
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 synthaseAn ATP synthase is a general term for an enzyme that can synthesize adenosine triphosphate from adenosine diphosphate and inorganic phosphate by using some form of energy...
. This
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
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
antiporterAn antiporter is an integral membrane protein which is involved in secondary active transport of two or more different molecules or ions An antiporter (also called exchanger or counter-transporter) is an integral membrane protein which is involved in secondary active transport of two or more...
, the
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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 proteinAn Integral Membrane Protein is a protein molecule that is permanently attached to the biological membrane...
used to exchange newly-synthesized ATP in the matrix for
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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-CoAAcetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main use 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 between coenzyme A and acetic...
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 FADH
2 molecule, which are used to generate ATP by oxidative phosphorylation. Because NADH and FADH
2 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
calorieThe calorie is a pre-SI metric unit of energy. The unit was first defined by Professor Nicolas Clément in 1824 as a unit of heat. This definition entered 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
fermentationFermentation is the process of deriving energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. This is in contrast to cellular respiration, where electrons are donated to an exogenous electron acceptor,...
entails the generation of energy via the process of oxidation in the absence of
O2Oxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
as an
electron acceptorAn 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 acidLactic acid , also known as milk acid, is a chemical compound that plays a role in several biochemical processes. It was first isolated in 1780 by a Swedish chemist, Carl Wilhelm Scheele, and is a carboxylic acid with a chemical formula of C
3H
6O
3...
is:
- C6H12O6 2CH3CH(OH)COOH + 2 ATP
In prokaryotes, multiple electron acceptors can be used in anaerobic respiration. These include
nitrateIn inorganic chemistry, a nitrate is a salt of nitric acid with an ion composed of one nitrogen and three oxygen atoms . In organic chemistry the esters of nitric acid and various alcohols are called nitrates.-Chemical properties:...
,
sulfateIn inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
or carbon dioxide. These processes lead to the ecologically-important processes of
denitrificationDenitrification is a microbially facilitated process of dissimilatory nitrate reduction that may ultimately produce molecular nitrogen through a series of intermediate gaseous nitrogen oxide products. This respiratory process reduces oxidized forms of nitrogen in response to the oxidation of an...
, sulfate reduction and
acetogenesisAcetogenesis is a process through which acetate is produced by anaerobic bacteria from a variety of energy and carbon sources...
, 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 family,
ATP production during photosynthesis
In plants, ATP is synthesized in thylakoid membrane of the
chloroplastChloroplasts 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.The word chloroplast is...
during the light-dependent reactions of
photosynthesisPhotosynthesis is a 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...
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 cycleThe Calvin cycle or Calvin-Benson-Bassham cycle is a series of biochemical reactions that take place in the stroma of chloroplasts in photosynthetic organisms. It was discovered by Melvin Calvin, James Bassham and Andrew Benson at the University of California, Berkeley by using the radioactive...
, which produces
trioseA triose is a monosaccharide containing three carbon atoms. There are only two trioses, an aldotriose and a ketotriose . Trioses are important in respiration...
sugars.
ATP recycling
The total quantity of ATP in the human body is about 0.1
moleThe mole is a unit of amount of substance: it is an SI base unit, and one of the few units used to measure this physical quantity. The name "mole" was coined in German by Wilhelm Ostwald in 1893, although the related concept of equivalent mass had been in use at least a century earlier...
. The majority of ATP is not usually synthesised
de novo, but is generated from
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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 +
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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
hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
of 100 to 150 moles of ATP daily which is around 50 to 75 kg. Typically, a human will use up their 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
feedbackFeedback describes the situation when output from an event or phenomenon in the past will influence the same event/phenomenon in the present or future....
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,
hexokinaseA 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 kinasePyruvate 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
phosphofructokinasePhosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by several 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 siteIn 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, or more specifically, protein ligands—form a chemical bond....
s for ATP - the
active siteThe active site of an enzyme contains the catalytic and binding sites. The structure and chemical properties of the active site allow the recognition and binding of the substrate....
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,
ammoniumThe ammonium cation is a positively charged polyatomic cation of the chemical formula NH. It has a formula weight of 18.05 and 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
calciumCalcium 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 grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
, inorganic phosphate, ATP,
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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.
CitrateA citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid...
- the molecule that gives its name to the cycle - is a feedback inhibitor of
citrate synthaseThe 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 oxidaseThe 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 cCytochrome c, 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...
. 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] [P
i] 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.
Functions in cells
ATP is generated in the cell by energy-consuming processes and is broken down by energy-releasing processes. In this way ATP transfers energy between spatially-separate
metabolic reactionsMetabolism is the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter,...
. ATP is the main energy source for the majority of cellular functions. This includes the synthesis of macromolecules, including
DNADNA replication, the basis for biological inheritance, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand...
,
RNATranscription, or RNA synthesis, is the process of creating an equivalent 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 in the presence of the correct enzymes...
, and
proteinsTranslation is the first stage of protein biosynthesis . Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA...
. ATP also plays a critical role in the transport of macromolecules across cell membranes, e.g.
exocytosisExocytosis is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
and
endocytosisEndocytosis is the process by which cells absorb molecules from outside the cell by engulfing it with their cell membrane. 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 membrane or cell membrane...
.
In the synthesis of the
nucleic acidA nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acid . Nucleic acids are universal in living things, as...
RNARibonucleic acid is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate...
, ATP is one of the four nucleotides incorporated directly into RNA molecules by
RNA polymeraseRNA 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
deoxyribonucleotideA 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 or more phosphate groups. The nitrogenous base is always bonded to the 1' carbon of the deoxyribose, which is...
dATP, before incorporation into DNA.
ATP is critically involved in maintaining cell structure by facilitating assembly and disassembly of elements of the
cytoskeletonThe cytoskeleton is a cellular "scaffolding" or "skeleton" contained within the cytoplasm. The cytoskeleton is present in all cells; it was once thought this structure was 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 crossbridgesThe sliding filament theory describes a process used by muscles to contract.-Process of movement:Myosin is a molecular motor that acts like an active ratchet. Chains of actin proteins form high tensile passive 'thin' filaments that transmit the force generated by myosin to the ends of the muscle. ...
required for
muscle contractionMuscle 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
locomotionAnimal locomotion, which is the act of self-propulsion by an animal, has many manifestations, including running, 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
respirationThe respiratory systems function is to allow gas exchange to all parts of the body. The space between the alveoli & the capillaries, the anatomy or structure of the exchange system, and the precise physiological uses of the exchanged gases vary depending on the organism...
.
Extracellular signalling
ATP is also a signalling molecule. ATP, ADP, or adenosine are recognised by purinergic receptors.
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-coupledG 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 P2Y
1 and P2Y
15, only nine members of the P2Y family have been cloned, and some are only related through weak homology and several (P2Y
5, P2Y
7, P2Y
9, P2Y
10) do not function as receptors that raise cytosolic calcium. The
P2X ionotropic receptor subgroup comprises seven members (P2X
1–P2X
7) which are ligand-gated Ca
2+-permeable ion channels that open when bound to an extracellular purine nucleotide. In contrast to P2 receptors (agonist order ATP >
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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
nucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism...
s like ATP are not strong agonists of P1 receptors which are strongly activated by
adenosineAdenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule moiety via a β-N
9-glycosidic bond....
and other
nucleosideNucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar. Examples of these include cytidine, uridine, adenosine, guanosine, thymidine and inosine....
s (ADO > AMP >
ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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.
Intracellular signalling
ATP is critical in
signal transductionIn biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers,...
processes. It is used by
kinaseIn chemistry and biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates. The process is referred to as phosphorylation...
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.
PhosphorylationPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many protein enzymes on and off, causing or preventing the mechanisms of diseases such as cancer and diabetes....
of a protein by a kinase can activate this cascade such as the
mitogen-activated protein kinaseMitogen-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.-Function:MAPKs are involved in the...
cascade.
ATP is also used by
adenylate cyclaseAdenylate cyclase is a lyase enzyme. It is a part of the cAMP-dependent pathway-Types:There are ten known adenylate cyclases in mammals:* ADCY1* ADCY2* ADCY3* ADCY4* ADCY5...
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.
Deoxyribonucleotide synthesis
In all known organisms, the deoxyribonucleotides that make up
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
are synthesized by the action of
ribonucleotide reductaseRibonucleotide 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. This enzyme reduces the 2'
hydroxylIn chemistry, hydroxyl is composed of molecules consisting of an oxygen atom and a hydrogen atom connected by a covalent bond . The neutral form is a hydroxyl radical. The hydroxyl anion is called hydroxide; it is a diatomic ion with a charge of negative one...
group on the
riboseRibose, primarily occurring as
D-ribose, is an organic compound that occurs widely in nature. It is an aldopentose, that is a monosaccharide containing five carbon atoms that, in its acyclic form, has an aldehyde functional group at one end. This species predominantly exists in the...
sugar to
deoxyriboseDeoxyribose, also known as
D-Deoxyribose and 2-deoxyribose, is an aldopentose — a monosaccharide containing five carbon atoms, and including an aldehyde functional group in its linear structure...
, forming a deoxyribonucleotide (denoted dATP). All ribonucleotide reductase enzymes use a common sulfhydryl
radicalIn chemistry, radicals are atoms, molecules, or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions...
mechanism reliant on reactive
cysteineCysteine is an α-amino acid with the chemical formula HO
2CCHCH
2SH. 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 nonpolar and thus cysteine is usually classified as...
residues that oxidize to form
disulfide bondIn 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 C-S-S-C. The terminology is widely used in biochemistry...
s in the course of the reaction. RNR enzymes are recycled by reaction with
thioredoxinThioredoxin is an enzyme that, in humans, is encoded by the TXN gene.- Function :Thioredoxins are proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange...
or
glutaredoxinGlutaredoxins are small redox enzymes of approximately one hundred amino-acid residues which 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 synthesisDNA replication, the basis for biological inheritance, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand...
and
DNA repairDNA 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
mutagenIn biology, a mutagen is a physical or chemical agent that changes the genetic material of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are typically also carcinogens...
ic due to the increased likelihood of the
DNA polymeraseA DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their 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
hypoxiaHypoxia 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...
.
Binding to proteins
Some proteins that bind ATP do so in a characteristic
protein foldIn biochemistry and chemistry, 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 foldThe Rossmann fold is a protein structural motif found in proteins that bind nucleotides, especially the cofactor NAD. The structure is composed of three or more parallel beta strands linked by two alpha helices in the topological order beta-alpha-beta-alpha-beta...
, which is a general
nucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism...
-binding structural domain that can also bind the cofactor
NADNicotinamide 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, with one nucleotide containing an adenine base and the other containing...
. The most common ATP-binding proteins, known as kinases, share a small number of common folds; the
protein kinaseA 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 generally requires the presence of a
divalentIn chemistry, divalent anions are atoms or radicals with 2 additional electrons when compared to their elemental state ; for instance, S2- is the sulfide anion. Conversely, a cation is missing some electrons as compared with the neutral atom. Example: iron or Fe2+ is the...
cation, almost always
magnesiumMagnesium 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 by mass, although ninth in the Universe as a whole...
, which binds to the ATP phosphate groups. The presence of magnesium greatly decreases the
dissociation constantIn 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 vitroA procedure performed in vitro is performed not in a living organism but in a controlled environment, such as in a test tube or Petri dish...
studies to explore ATP-dependent molecular processes.
Enzyme inhibitorEnzyme inhibitors are molecules that bind to enzymes and decrease 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
kinaseIn chemistry and biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates. The process is referred to as phosphorylation...
s are needed to examine the
binding siteIn 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, or more specifically, protein ligands—form a chemical bond....
s and
transition stateThe 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...
s involved in ATP-dependent reactions. ATP analogs are also used in
X-ray crystallographyX-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 diffracts into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture...
to determine a
protein structureProteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen, and sulphur. All proteins are polymers of amino acids. According to their physical size, proteins are nanoparticles...
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
sulfurSulfur or sulphur is the chemical element that has the atomic number 16. It is denoted with the symbol S. It is an abundant, multivalent non-metal. Sulfur, in its native form, is a yellow crystalline solid. In nature, it can be found as the pure element and as sulfide and sulfate minerals...
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
vanadateIn 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...
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, abbreviated ADP, is a nucleotide. 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....
(ADPAdenosine diphosphate, abbreviated ADP, is a nucleotide. 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 , also known as 5'-adenylic acid, is a nucleotide that is found in RNA. It is an ester of phosphoric acid and the nucleoside adenosine...
(AMP)
- Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
(cAMP)
- ATPases
- ATP Test
- 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
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or more rarely, the Szent-Györgyi-Krebs cycle — is a series of enzyme-catalysed chemical reactions, which is of central importance in all living cells that use oxygen as part of cellular respiration...
(also called the Krebs cycle or TCA cycle)
- 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 factors are proteins that stimulate the exchange of nucleoside diphosphates for nucleoside triphosphates bound to other proteins.-Function:...
- Mitochondria
- 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 oxidation-reduction reactions...
External links