Ion transporter

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In biology, an ion transporter (or ion pump) is a transmembrane protein that moves ions across a biological membrane against their concentration gradient through active transport. [1] These primary transporters are enzymes that convert energy from various sources—including adenosine triphosphate (ATP), sunlight, and other redox reactions—to potential energy stored in an electrochemical gradient. This potential energy is then used by secondary transporters, including ion carriers and ion channels, to drive vital cellular processes, such as ATP synthesis. [2]

Transmembrane protein protein spanning across a biological membrane

A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane to which it is permanently attached. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane.

Biological membrane enclosing or separating membrane that acts as a selectively permeable barrier within living thing

A biological membrane or biomembrane is an enclosing or separating membrane that acts as a selectively permeable barrier within living things. Biological membranes, in the form of eukaryotic cell membranes, consist of a phospholipid bilayer with embedded, integral and peripheral proteins used in communication and transportation of chemicals and ions. The bulk of lipid in a cell membrane provides a fluid matrix for proteins to rotate and laterally diffuse for physiological functioning. Proteins are adapted to high membrane fluidity environment of lipid bilayer with the presence of an annular lipid shell, consisting of lipid molecules bound tightly to surface of integral membrane proteins. The cell membranes are different from the isolating tissues formed by layers of cells, such as mucous membranes, basement membranes, and serous membranes.

In cellular biology, active transport is the movement of molecules across a membrane from a region of their lower concentration to a region of their higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses ATP, and secondary active transport that uses an electrochemical gradient. An example of active transport in human physiology is the uptake of glucose in the intestines.


Classification and disambiguation

Ion transporters are classified as a super family of transporters that contain 12 families of transporters. [3] These families are part of the Transport Classification (TC) system that is used by the International Union of Biochemistry and Molecular Biology (IUBMB) and are grouped according to characteristics such as the substrates being transported, the transport mechanism, the energy source used, and also by comparing the DNA sequences making up each protein. The most important unifying factor being the charged nature of the substrate which indicates the transport of an ion and not a neutral species. [3]

The ion transporter (IT) superfamily is a superfamily of secondary carriers that transport charged substrates.

A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion or active transport. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans.

The International Union of Biochemistry and Molecular Biology (IUBMB) is an international non-governmental organisation concerned with biochemistry and molecular biology. Formed in 1955 as the International Union of Biochemistry, the union has presently 77 member countries.

ATP synthase uses a chemical (proton) gradient to generate ATP ATP-Synthase.svg
ATP synthase uses a chemical (proton) gradient to generate ATP

Ion transporters differ significantly from ion channels. An electrochemical gradient or concentration gradient is a difference in concentration of a chemical molecule or ion in two separate areas. [4] At equilibrium the concentrations of the ion in both areas will be equal, so if there is a difference in concentration the ions will seek to flow "down" the concentration gradient or from a high concentration to low concentration. Ion channels allows the specific ions that will fit into the channel to flow down their concentration gradient, equalizing the concentrations on either side of the cell membrane. Ion channels accomplish this via facilitated diffusion which is a type of passive transport. In contrast, ion transporters perform active transport by moving ions against their concentration gradient. [1] Using energy sources such as ATP, ion transporters are able to move ions against their concentration gradient which can then be used by secondary transporters or other proteins as a source of energy. [4]

Ion channel Pore-forming membrane proteins whose functions include gating the flow of ions across the cell membrane

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 ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all excitable cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

Facilitated diffusion

Facilitated diffusion is the process of spontaneous passive transport of molecules or ions across a biological membrane via specific transmembrane integral proteins. Being passive, facilitated transport does not directly require chemical energy from ATP hydrolysis in the transport step itself; rather, molecules and ions move down their concentration gradient reflecting its diffusive nature.

Passive transport

Passive transport is a movement of ions and other atomic or molecular substances across cell membranes without need of energy input. Unlike active transport, it does not require an input of cellular energy because it is instead driven by the tendency of the system to grow in entropy. The rate of passive transport depends on the permeability of the cell membrane, which, in turn, depends on the organization and characteristics of the membrane lipids and proteins. The four main kinds of passive transport are simple diffusion, facilitated diffusion, filtration, and/or osmosis.

Energy source

Primary transport

Primary transporters use energy to transport ions such as Na +, K+, and Ca2+ across a cells membrane and can create concentration gradients. [4] This transport usually uses ATP as an energy source but can also generate ATP through methods such as the electron transport chain in plants. [1] [4]

ATP utilizing

Transporters that use ATP convert the energy in ATP into potential energy in the form of a concentration gradient. They use the ATP to transport an ion from a low concentration to a higher concentration. Examples of proteins that use ATP are P-type ATPases that transfer Na +, K+, and Ca2+ ions by phosphorylation, A-type ATPases that transfer anions, and ABC transporters (ATP binding and cassette transporters) that transport a broad set of molecules. [4] Examples of the P-type ATPase include Na+/K+-ATPase [1] that is regulated by Janus Kinase-2 [5] as well as Ca2+ ATPase which exhibits sensitivity to ADP and ATP concentrations [2] P-glycoprotein is an example of an ABC transport binding protein in the human body.

P-type ATPase

The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. P-type ATPases are α-helical bundle primary transporters named based upon their ability to catalyze auto- (or self-) phosphorylation (hence P) of a key conserved aspartate residue within the pump and their energy source, adenosine triphosphate (ATP). In addition, they all appear to interconvert between at least two different conformations, denoted by E1 and E2. P-type ATPases fall under the P-type ATPase (P-ATPase) Superfamily (TC# 3.A.3) which, as of early 2016, includes 20 different protein families.

ATP-binding cassette transporter transmembrane protein

The ATP-binding cassette transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans.

Plasma membrane Ca<sup>2+</sup> ATPase

The plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cells and functions to remove calcium (Ca2+) from the cell. PMCA function is vital for regulating the amount of Ca2+ within all eukaryotic cells. There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important that they maintain low concentrations of Ca2+ for proper cell signalling. Thus, it is necessary for cells to employ ion pumps to remove the Ca2+. The PMCA and the sodium calcium exchanger (NCX) are together the main regulators of intracellular Ca2+ concentrations. Since it transports Ca2+ into the extracellular space, the PMCA is also an important regulator of the calcium concentration in the extracellular space.

ATP producing

ATP producing transporters run in the opposite direction of ATP Utilizing transporters. These proteins transport ions from high to low concentration with the gradient but in the process ATP is formed. Potential energy in the form of the concentration gradient is used to generate ATP. [4] In animals, this ATP synthesis takes place in the mitochondria using F- type ATPase otherwise known as ATP synthase. V-type ATPase serves the opposite function as F-type ATPase and is used in plants to hydrolyze ATP to create a proton gradient. Examples of this are lysosomes that use V-type ATPase acidify vesicles or plant vacuoles during process of photosynthesis in the chloroplasts. [1] This process can be regulated through various methods such as pH. [6]


F-ATPase, also known as F-Type ATPase, is an ATPase found in bacterial plasma membranes, in mitochondrial inner membranes, and in chloroplast thylakoid membranes. It uses a proton gradient to drive ATP synthesis by allowing the passive flux of protons across the membrane down their electrochemical gradient and using the energy released by the transport reaction to release newly formed ATP from the active site of F-ATPase. In some bacteria, sodium ions may be used instead of protons. Together with V-ATPases and A-ATPases, F-ATPases belong to superfamily of related ATP synthases.

ATP synthase enzyme

ATP synthase is an enzyme that creates the energy storage molecule adenosine triphosphate (ATP). ATP is the most commonly used "energy currency" of cells for all organisms. It is formed from adenosine diphosphate (ADP) and inorganic phosphate (Pi). The overall reaction catalyzed by ATP synthase is:


Vacuolar-type H+
(V-ATPase) is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pump protons across the plasma membranes of numerous cell types. V-ATPases couple the energy of ATP hydrolysis to proton transport across intracellular and plasma membranes of eukaryotic cells. It is generally seen as the polar opposite of ATP synthase because ATP synthase is a proton channel that uses the energy from a proton gradient to produce ATP. V-ATPase however, is a proton pump that uses the energy from ATP hydrolysis to produce a proton gradient.

Secondary transport


Secondary transporters also transport ions against the concentration gradient – from low concentration to high concentration - but unlike primary transporters who use ATP to create a concentration gradient, secondary transporters use the potential energy from the concentration gradient created by the primary transporters to transport ions. [4] Symporters such as the Sodium-chloride symporter transport an ion with its concentration gradient, and they couple the transport of a second molecule in the same direction. Antiporters also use the concentration gradient but the coupled molecule is transported in the opposite direction. [4]


Ion transporters can be regulated in a variety of different ways such as phosphorylation, allosteric inhibition or activation, and sensitivity to ion concentration. Using protein kinases to add a phosphate group or phosphatases to dephosphorylate the protein can change the activity of the transporter. [7] Whether the protein is activated or inhibited with the addition of the phosphate group depends on the specific protein. With allosteric inhibition, the regulatory ligand can bind into the regulatory site and either inhibit or activate the transporter. Ion transporters can also be regulated by the concentration of an ion (not necessarily the ion it transfers) in solution. For example, the electron transport chain is regulated by the presence of H+ ions (pH) in solution. [4]

Table of ion transporters

Ion Transporters
Neurotransmitter transporter
Glutamate transporter
Monoamine transporter
GABA transporters
Glycine transporters
Adenosine transporters
Plasma membrane Ca2+ ATPase
Sodium-calcium exchanger
Sodium-chloride symporter

See also

Related Research Articles

Adenosine triphosphate chemical compound

Adenosine triphosphate (ATP) is a complex organic chemical that provides energy to drive many processes in living cells, e.g. muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP so that the human body recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme.

Oxidative phosphorylation the phosphorylation of ADP to ATP that accompanies the oxidation of a metabolite through the operation of the respiratory chain. Oxidation of compounds establishes a proton gradient across the membrane, providing the energy for ATP synthesis.

Oxidative phosphorylation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy which is used to produce adenosine triphosphate (ATP). In most eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative fermentation processes such as anaerobic glycolysis.

Adenosine diphosphate chemical compound

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 attached to adenine and two phosphate groups bonded to the 5 carbon atom of ribose. The diphosphate group of ADP is attached to the 5’ carbon of the sugar backbone, while the adenosine attaches to the 1’ carbon.

A proton pump is an integral membrane protein that builds up a proton gradient across a biological membrane. Proton pumps catalyze the following reaction:

Cellular respiration Cellular enzymatic release of energy from compounds

Cellular respiration is a set of metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. The reactions involved in respiration are catabolic reactions, which break large molecules into smaller ones, releasing energy in the process, as weak so-called "high-energy" bonds are replaced by stronger bonds in the products. Respiration is one of the key ways a cell releases chemical energy to fuel cellular activity. Cellular respiration is considered an exothermic redox reaction which releases heat. The overall reaction occurs in a series of biochemical steps, most of which are redox reactions themselves. Although cellular respiration is technically a combustion reaction, it clearly does not resemble one when it occurs in a living cell because of the slow release of energy from the series of reactions.


ATPases (EC, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, adenosine 5'-triphosphatase, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3-ATPase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or the inverse reaction. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.

Na<sup>+</sup>/K<sup>+</sup>-ATPase enzyme

Na⁺/K⁺-ATPase is an enzyme found in the plasma membrane of all animal cells. It performs several functions in cell physiology.

Digestion is the breakdown of carbohydrates to yield an energy rich compound called ATP. The production of ATP is achieved through the oxidation of glucose molecules. In oxidation, the electrons are stripped from a glucose molecule to reduce NAD+ and FAD. NAD+ and FAD possess a high energy potential to drive the production of ATP in the electron transport chain. ATP production occurs in the mitochondria of the cell. There are two methods of producing ATP: aerobic and anaerobic. In aerobic respiration, oxygen is required. Oxygen plays a key role as it increases ATP production from 4 ATP molecules to about 30 ATP molecules. In anaerobic respiration, oxygen is not required. When oxygen is absent, the generation of ATP continues through fermentation.There are two types of fermentation: alcohol fermentation and lactic acid fermentation.


Chemiosmosis is the movement of ions across a semipermeable membrane, down their electrochemical gradient. An example of this would be the generation of adenosine triphosphate (ATP) by the movement of hydrogen ions (H+) across a membrane during cellular respiration or photosynthesis.


Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.

Mitochondrial matrix The gel-like material, with considerable fine structure, that lies in the matrix space, or lumen, of a mitochondrion. It contains the enzymes of the tricarboxylic acid cycle and, in some organisms, the enzymes concerned with fatty acid oxidation.

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 mitochondria's DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate and the beta oxidation of fatty acids.

Electrochemical gradient gradient of electrochemical potential, usually for an ion that can move across a membrane

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 electrical gradient, or difference in charge across a membrane. When there are unequal concentrations of an ion across a permeable membrane, the ion will move across the membrane from the area of higher concentration to the area of lower concentration through simple diffusion. Ions also carry an electric charge that forms an electric potential across a membrane. If there is an unequal distribution of charges across the membrane, then the difference in electric potential generates a force that drives ion diffusion until the charges are balanced on both sides of the membrane.

Sodium-dependent glucose cotransporters are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron. They contribute to renal glucose reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be reabsorbed along the nephron. If the plasma glucose concentration is too high (hyperglycemia), glucose is excreted in urine (glucosuria) because SGLT are saturated with the filtered glucose. Glucose is never secreted by a healthy nephron.

Selective reabsorption is the process whereby certain molecules, after being filtered out of the capillaries along with nitrogenous waste products and water in the glomerulus, are reabsorbed from the filtrate as they pass through the nephron. Selective reabsorbtion occurs in the PCT. The PCT is highly permeable meaning it is easy for molecules to diffuse through it.


A symporter is an integral membrane protein that is involved in the transport of many differing types of molecules across the cell membrane. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time, and is, therefore, a type of cotransporter. The transporter is called a symporter, because the molecules will travel in the same direction in relation to each other. This is in contrast to the antiport transporter. Typically, the ion(s) will move down the electrochemical gradient, allowing the other molecule(s) to move against the concentration gradient. The movement of the ion(s) across the membrane is facilitated diffusion, and is coupled with the active transport of the molecule(s).

ATP synthase alpha/beta subunits

ATPases are membrane-bound enzyme complexes/ion transporters that combine ATP synthesis and/or hydrolysis with the transport of protons across a membrane. ATPases can harness the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.


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