An uncoupler or uncoupling agent is a molecule that disrupts

oxidative phosphorylation Oxidative phosphorylation(UK , US : or electron transport-linked phosphorylation or terminal oxidation, is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order ...

prokaryotes A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...

and

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 us ...

or photophosphorylation in

chloroplasts A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...

and

cyanobacteria Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteri ...

by dissociating the reactions of ATP synthesis from the

electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...

. The result is that the cell or mitochondrion expends energy to generate a

proton-motive force Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An important example is the formation of adenosine triphosphate (ATP) by the movement of hydrogen ions (H+) across a membra ...

, but the proton-motive force is dissipated before the

ATP synthase ATP synthase is an enzyme that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). ATP synthase is a molecular machine. The overall reaction catalyzed ...

can recapture this energy and use it to make ATP. Because the intracellular supply of protons is replenished, uncouplers actually stimulate cellular metabolism and oxygen consumption (despite their inhibitory effects on oxidative phosphorylation) and increase the energy cost of generating ATP. Uncouplers are capable of transporting protons through mitochondrial and lipid membranes.

Description

Classical uncouplers have five properties: # the complete release of respiratory control # the substitution of all coupled processes ( ATP synthesis, transhydrogenation, reverse electron flow,

active transport In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellula ...

of cations, etc.) by a cyclic proton transport mediated by the uncoupler # the elimination of all protonic and cationic gradients generated across the mitochondrial or prokaryotic membrane # no discrimination in these actions between one coupling site and another # no discrimination between coupled processes driven by electron transfer and coupled processes driven by ATP hydrolysis Pseudo-uncouplers show one or more of these properties, but not all, and thus must be combined with one or more other pseudo-uncouplers to achieve full uncoupling.

Classical uncouplers

The following compounds are known to be classical uncouplers: * 2,4-dinitrophenol (DNP) * 2,5-di nitrophenol * 1799 (α,α′-bis(hexafluoracetonyl)acetone) * BAM15, ''N''⁵,''N''⁶-bis(2-fluorophenyl)- ,2,5xadiazolo ,4-''b''yrazine-5,6-diamine * 2-''tert''-butyl-4,6-dinitrophenol (Dinoterb) * 6-''sec''-butyl-2,4-dinitrophenol (Dinoseb) * C₄R1 (a short-chain alkyl derivative of rhodamine 19) * Carbonyl cyanide phenylhydrazone (CCP) * Carbonyl cyanide ''m''-chlorophenyl hydrazone (CCCP) * Carbonyl cyanide-''p''-trifluoromethoxyphenyl hydrazone (FCCP) * CDE () (produced by Verbesina) * Chlorfenapyr (after N-dealkylation by P450, an insecticide in IRAC group 13) * CZ5 * Desaspidin * Dicoumarol * Dinitro-''ortho''-cresol (DNOC) *

Ellipticine Ellipticine is a tetracyclic alkaloid first extracted from the tree species ''Ochrosia elliptica'' and ''Rauvolfia sandwicensis'' which inhibits the enzyme topoisomerase II via intercalation (biochemistry), intercalative binding to DNA. ...

* Endosidin 9 (ES9) * Flufenamic acid * Niclosamide ethanolamine (NEN) * Ppc-1 (a

secondary metabolite Secondary metabolites, also called ''specialised metabolites'', ''secondary products'', or ''natural products'', are organic compounds produced by any lifeform, e.g. bacteria, archaea, fungi, animals, or plants, which are not directly involved ...

produced by '' Polysphondylium pseudocandidum'') * Pentachlorophenol (PCP) * Perfluorotriethylcarbinol * S-13 (5-chloro-3-''t''-butyl-2′-chloro-4′-nitro salicylanilide) * TTFB (4,5,6,7-tetrachloro-2-trifluoromethyl

benzimidazole Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals. Preparation Benzimi ...

) * Malonoben (tyrphostin A9, SF-6847, AG17) * (+)- usnic acid * XCT-790 * mitoFluo (10- -(3-hydroxy-6-oxo-xanthen-9-yl)benzoylxydecyl-triphenyl-phosphonium bromide) *

Triclosan Triclosan (sometimes abbreviated as TCS) is an antibacterial and antifungal agent present in some consumer products, including toothpaste, soaps, detergents, toys, and surgical cleaning treatments. It is similar in its uses and mechanism of act ...

(Trichloro-2'-hydroxydiphenyl ether) * Pyrrolomycin C (produced by Genus Streptomyces) *

Salicylic acid Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or white), bitter-tasting solid, it is a precursor to and a active metabolite, metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been lis ...

(if taken in extreme excess)

Pseudo-uncouplers

The following compounds are known to be pseudo-uncouplers: *

Azide In chemistry, azide (, ) is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant ...

* Biguanides *

Bupivacaine Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease sensation in a specific small area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural ...

* Calcimycin ( A23187) * Dodecyltriphenyl

phosphonium In chemistry, the term phosphonium (more obscurely: phosphinium) describes polyatomic cations with the chemical formula (where R is a hydrogen or an alkyl, aryl, organyl or halogen group). These cations have tetrahedral structures. The ...

(C₁₂TPP) * Lasalocid (X537A) * Long-chain fatty acids, such as

linoleic acid Linoleic acid (LA) is an organic compound with the formula . Both alkene groups () are ''cis''. It is a fatty acid sometimes denoted 18:2 (n−6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid. Linoleic acid is a polyunsat ...

* MitoQ10 * Nigericin *

Picric acid Picric acid is an organic compound with the formula (O2N)3C6H2OH. Its IUPAC name is 2,4,6-trinitrophenol (TNP). The name "picric" comes from (''pikros''), meaning "bitter", due to its bitter taste. It is one of the most acidic phenols. Like ot ...

(2,4,6-trinitrophenol) * Sodium tetraphenylborate * SR4 (1,3-bis(dichlorophenyl)urea 13) * Tetraphenylphosphonium chloride * Valinomycin *

Arsenate The arsenate is an ion with the chemical formula . Bonding in arsenate consists of a central arsenic atom, with oxidation state +5, double bonded to one oxygen atom and single bonded to a further three oxygen atoms. The four oxygen atoms orien ...

Notes

References

External links