Chemiosmosis is the movement of
ions across a
semipermeable membrane
Semipermeable membrane is a type of biological or synthetic, polymeric membrane that will allow certain molecules or ions to pass through it by osmosis. The rate of passage depends on the pressure, concentration, and temperature of the molecul ...
bound structure, down their
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...
. An important example is the formation of
adenosine triphosphate (ATP) by the movement of
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
ions (H
+) across a
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...
during
cellular respiration
Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be des ...
or
photosynthesis
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored in ...
.
Hydrogen ions, or
proton
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...
s, will
diffuse
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
from a region of high proton concentration to a region of lower proton concentration, and an
electrochemical concentration gradient of protons across a membrane can be harnessed to make ATP. This process is related to
osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region ...
, the movement of
water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
across a selective membrane, which is why it is called "chemiosmosis".
ATP synthase
ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...
is the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that makes ATP by chemiosmosis. It allows protons to pass through the membrane and uses the
free energy difference to
phosphorylate adenosine diphosphate
Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbone ...
(ADP), making ATP. The generation of ATP by chemiosmosis occurs in
mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
and
chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it i ...
s, as well as in most
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
. For instance, in
chloroplasts
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, ...
during photosynthesis, an electron transport chain pumps H
+ ions (protons) in the
stroma (fluid)
Stroma, in botany, refers to the colorless fluid surrounding the grana within the chloroplast.
Within the stroma are grana (stacks of thylakoid), and the sub-organelles or daughter cells, where photosynthesis is commenced before the chemical c ...
through the thylakoid membrane to the thylakoid spaces. The stored energy is used to photophosphorylate ADP, making ATP, as protons move through ATP synthase.
The chemiosmotic theory
Peter D. Mitchell
Peter Dennis Mitchell, FRS (29 September 1920 – 10 April 1992) was a British biochemist who was awarded the 1978 Nobel Prize for Chemistry for his discovery of the chemiosmotic mechanism of ATP synthesis.
Education and early life
Mitc ...
proposed the chemiosmotic hypothesis in 1961. The theory suggests essentially that most
adenosine triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
(ATP) synthesis in
respiring cells comes from the
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...
across the inner membranes of
mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
by using the
energy
In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of heat a ...
of
NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
and
FADH2 formed from the breaking down of energy-rich
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
s such as
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
.
Molecules such as glucose are
metabolized
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
to produce
acetyl CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
as a fairly energy-rich intermediate. The
oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
of
acetyl coenzyme A
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
(acetyl-CoA) in the
mitochondrial matrix
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribo ...
is coupled to the
reduction of a carrier molecule such as
nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
(NAD) and
flavin adenine dinucleotide
Flavin may refer to:
Placename
* Flavin, Aveyron, a commune in southern France
Surname
* Adrian Flavin (born 1979), a professional rugby player
* Christopher Flavin, president of the Worldwatch Institute
* Dan Flavin (1933–1996), a minimalis ...
(FAD).
The carriers pass
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no kn ...
s to the
electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
(ETC) in the
inner mitochondrial membrane
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
Structure
The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...
, which in turn pass them to other proteins in the ETC. The
energy of the oxygen, the terminal acceptor in the ETC, is used to pump
proton
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...
s from the
matrix
Matrix most commonly refers to:
* ''The Matrix'' (franchise), an American media franchise
** ''The Matrix'', a 1999 science-fiction action film
** "The Matrix", a fictional setting, a virtual reality environment, within ''The Matrix'' (franchis ...
into the intermembrane space, storing energy in the form of a transmembrane
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...
. The protons move back across the inner membrane through the enzyme
ATP synthase
ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...
. The flow of protons back into the matrix of the mitochondrion via
ATP synthase
ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...
provides enough energy for ADP to combine with inorganic
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
to form ATP.
This was a radical proposal at the time, and was not well accepted. The prevailing view was that the energy of electron transfer was stored as a stable high potential intermediate, a chemically more conservative concept. The problem with the older paradigm is that no high energy intermediate was ever found, and the evidence for proton pumping by the complexes of the
electron transfer chain
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...
grew too great to be ignored. Eventually the weight of evidence began to favor the chemiosmotic hypothesis, and in 1978 Peter Mitchell was awarded the
Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
.
Chemiosmotic coupling is important for ATP production in
mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
,
chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it i ...
s
and many
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
.
Proton-motive force
The movement of ions across the membrane depends on a combination of two factors:
#
Diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
force caused by a concentration gradient - all particles tend to diffuse from higher concentration to lower.
#
Electrostatic force
Coulomb's inverse-square law, or simply Coulomb's law, is an experimental law of physics that quantifies the amount of force between two stationary, electrically charged particles. The electric force between charged bodies at rest is convention ...
caused by
electrical potential
The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is defined as the amount of work energy needed to move a unit of electric charge from a reference point to the specific point in ...
gradient -
cations
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
like protons H
+ tend to diffuse down the electrical potential, from the positive (P) side of the membrane to the negative (N) side.
Anions
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
diffuse spontaneously in the opposite direction.
These two gradients taken together can be expressed as an
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...
.
Lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
s of
biological membrane
A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ce ...
s, however, are barriers for ions. This is why energy can be stored as a combination of these two gradients across the membrane. Only special membrane proteins like
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s can sometimes allow ions to move across the membrane (see also:
Membrane transport
In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them. Th ...
). In chemiosmotic theory transmembrane
ATP synthase
ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...
s are very important. They convert energy of spontaneous flow of protons through them into chemical energy of ATP bonds.
Hence researchers created the term proton-motive force (PMF), derived from the electrochemical gradient mentioned earlier. It can be described as the measure of the potential energy stored (
chemiosmotic potential
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and th ...
) as a combination of proton and voltage (electrical potential) gradients across a membrane. The electrical gradient is a consequence of the charge separation across the membrane (when the protons H
+ move without a
counterion
160px, Polystyrene sulfonate, a cation-exchange resin, is typically supplied with as the counterion.">cation-exchange_resin.html" ;"title="Polystyrene sulfonate, a cation-exchange resin">Polystyrene sulfonate, a cation-exchange resin, is typical ...
, such as
chloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
Cl
−).
In most cases the proton-motive force is generated by an electron transport chain which acts as a proton pump, using the
Gibbs free energy
In thermodynamics, the Gibbs free energy (or Gibbs energy; symbol G) is a thermodynamic potential that can be used to calculate the maximum amount of work that may be performed by a thermodynamically closed system at constant temperature and pr ...
of
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
reactions to pump protons (hydrogen ions) out across the membrane, separating the charge across the membrane. In mitochondria, energy released by the electron transport chain is used to move protons from the mitochondrial matrix (N side) to the intermembrane space (P side). Moving the protons out of the mitochondrion creates a lower concentration of positively charged protons inside it, resulting in excess negative charge on the inside of the membrane. The electrical potential gradient is about -170 mV , negative inside (N). These gradients - charge difference and the proton concentration difference both create a combined electrochemical gradient across the membrane, often expressed as the proton-motive force (PMF). In mitochondria, the PMF is almost entirely made up of the electrical component but in chloroplasts the PMF is made up mostly of the pH gradient because the charge of protons H
+ is neutralized by the movement of Cl
− and other anions. In either case, the PMF needs to be greater than about 460 mV (45 kJ/mol) for the ATP synthase to be able to make ATP.
Equations
The proton-motive force is derived from the
Gibbs free energy
In thermodynamics, the Gibbs free energy (or Gibbs energy; symbol G) is a thermodynamic potential that can be used to calculate the maximum amount of work that may be performed by a thermodynamically closed system at constant temperature and pr ...
. Let N denote the inside of a cell, and let P denote the outside. Then
:
where
*
is the Gibbs free energy change per unit amount of
cation
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s transferred from P to N;
*
is the
charge number
Charge number (''z'') refers to a quantized value of electric charge, with the quantum of electric charge being the elementary charge, so that the charge number equals the electric charge (''q'') in coulombs divided by the elementary-charge con ...
of the
cation
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
;
*
is the electric potential of N relative to P;
*
and
are the cation concentrations at P and N, respectively;
*
is the
Faraday constant
In physical chemistry, the Faraday constant, denoted by the symbol and sometimes stylized as ℱ, is the electric charge per mole of elementary charges. It is named after the English scientist Michael Faraday. Since the 2019 redefinition of S ...
;
*
is the
gas constant
The molar gas constant (also known as the gas constant, universal gas constant, or ideal gas constant) is denoted by the symbol or . It is the molar equivalent to the Boltzmann constant, expressed in units of energy per temperature increment per ...
; and
*
is the
temperature
Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer.
Thermometers are calibrated in various temperature scales that historically have relied o ...
.
The molar Gibbs free energy change
is frequently interpreted as a molar electrochemical ion potential
.
For an electrochemical proton gradient
and as a consequence:
:
where
:
.
Mitchell defined the proton-motive force (PMF) as
:
.
For example,
implies
. At
this equation takes the form:
.
Note that for spontaneous proton import from the P side (relatively more positive and acidic) to the N side (relatively more negative and alkaline),
is negative (similar to
) whereas PMF is positive (similar to redox cell potential
).
It is worth noting that, as with any transmembrane transport process, the PMF is directional. The sign of the transmembrane electric potential difference
is chosen to represent the change in potential energy per unit charge flowing into the cell as above. Furthermore, due to redox-driven proton pumping by coupling sites, the proton gradient is always inside-alkaline. For both of these reasons, protons flow in spontaneously, from the P side to the N side; the available free energy is used to synthesize ATP (see below). For this reason, PMF is defined for proton import, which is spontaneous. PMF for proton export, i.e., proton pumping as catalyzed by the coupling sites, is simply the negative of PMF(import).
The spontaneity of proton import (from the P to the N side) is universal in all bioenergetic membranes. This fact was not recognized before the 1990s, because the chloroplast thylakoid lumen was interpreted as an interior phase, but in fact it is topologically equivalent to the exterior of the chloroplast. Azzone et al. stressed that the inside phase (N side of the membrane) is the bacterial cytoplasm, mitochondrial matrix, or chloroplast stroma; the outside (P) side is the bacterial periplasmic space, mitochondrial intermembrane space, or chloroplast lumen. Furthermore, 3D tomography of the mitochondrial inner membrane shows its extensive invaginations to be stacked, similar to thylakoid disks; hence the mitochondrial intermembrane space is topologically quite similar to the chloroplast lumen.:
The energy expressed here as Gibbs free energy, electrochemical proton gradient, or proton-motive force (PMF), is a combination of two gradients across the membrane:
* the concentration gradient (via
) and
* electric potential gradient
.
When a system reaches equilibrium,
; nevertheless, the concentrations on either side of the membrane need not be equal. Spontaneous movement across the potential membrane is determined by both concentration and electric potential gradients.
The molar Gibbs free energy
of ATP synthesis
:
is also called phosphorylation potential. The equilibrium concentration ratio