An uncoupler or uncoupling agent is a molecule that disrupts oxidative phosphorylation in prokaryotes and mitochondria or

photophosphorylation In the process of photosynthesis, the phosphorylation of ADP to form ATP using the energy of sunlight is called photophosphorylation. Cyclic photophosphorylation occurs in both aerobic and anaerobic conditions, driven by the main primary source of ...

chloroplasts 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 in ...

and cyanobacteria by dissociating the reactions of ATP synthesis from the electron transport chain. 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 can recapture this energy and use it to make 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 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 ...

, transhydrogenation,

reverse electron flow Reverse electron flow (also known as reverse electron transport) is a mechanism in microbial metabolism. Chemolithotrophs using an electron donor with a higher redox potential than NAD(P)+/NAD(P)H, such as nitrite or sulfur compounds, must use ene ...

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 cellul ...

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 2,4-Dinitrophenol (2,4-DNP or simply DNP) is an organic compound with the formula HOC6H3(NO2)2. It is a yellow, crystalline solid that has a sweet, musty odor. It sublimates, is volatile with steam, and is soluble in most organic solvents as well ...

(DNP) * 2,5-di

nitrophenol Nitrophenols are compounds of the formula HOC6H5−x(NO2)x. The conjugate bases are called nitrophenolates. Nitrophenols are more acidic than phenol itself. Mono-nitrophenols with the formula HOC6H4NO2. Three isomeric nitrophenols exist: ...

* 1799 (α,α′-bis(hexafluoracetonyl)acetone) * BAM15, ''N''⁵,''N''⁶-bis(2-fluorophenyl)-

,2,5 The comma is a punctuation mark that appears in several variants in different languages. It has the same shape as an apostrophe or single closing quotation mark () in many typefaces, but it differs from them in being placed on the baseline ...

xadiazolo ,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 Rhodamine is a family of related dyes, a subset of the triarylmethane dyes. They are derivatives of xanthene. Important members of the rhodamine family are Rhodamine 6G, Rhodamine 123, and Rhodamine B. They are mainly used to dye paper and inks ...

19) * Carbonyl cyanide

phenylhydrazone Hydrazones are a class of organic compounds with the structure . They are related to ketones and aldehydes by the replacement of the oxygen =O with the = functional group. They are formed usually by the action of hydrazine on ketones or aldehydes. ...

(CCP) * Carbonyl cyanide ''m''-chlorophenyl hydrazone (CCCP) * Carbonyl cyanide-''p''-trifluoromethoxyphenyl hydrazone (FCCP) * CDE () (produced by Verbesina) * CZ5 * Desaspidin *

Dicoumarol Dicoumarol ( INN) or dicumarol (USAN) is a naturally occurring anticoagulant drug that depletes stores of vitamin K (similar to warfarin, a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of reductases. ...

* Dinitro-''ortho''-cresol (DNOC) *

Ellipticine Ellipticine is an alkaloid first extracted from trees of the species '' Ochrosia elliptica'' and ''Rauvolfia sandwicensis'', which inhibits the enzyme topoisomerase II via intercalative binding to DNA. Natural occurrence and synthe ...

* Endosidin 9 (ES9) *

Flufenamic acid Flufenamic acid (FFA) is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs). Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of pr ...

Niclosamide Niclosamide, sold under the brand name Niclocide among others, is an anthelmintic medication used to treat tapeworm infestations, including diphyllobothriasis, hymenolepiasis, and taeniasis. It is not effective against other worms such as flukes ...

ethanolamine (NEN) * Ppc-1 (a

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

produced by ''

Polysphondylium pseudocandidum ''Polysphondylium'' is a genus of cellular slime mold, including the species '' Polysphondylium pallidum''. The genus was circumscribed by German mycologist Julius Oscar Brefeld in 1884. Species *'' Polysphondylium acuminatum'' Vadell & Cavende ...

'') * Pentachlorophenol (PCP) * Perfluorotriethylcarbinol * S-13 (5-chloro-3-''t''-butyl-2′-chloro-4′-nitro

salicylanilide Salicylanilide is a chemical compound which is the amide of salicylic acid and aniline. It is classified as both a salicylamide and an anilide. Derivatives of salicylanilide have a variety of pharmacological uses. Chlorinated derivatives includi ...

) * SF 6847 (3,5-di-''t''-butyl-4-hydroxybenzylidine

malononitrile Malononitrile is an organic compound nitrile with the formula . It is a colorless or white solid. It can be prepared by dehydration of cyanoacetamide. Malononitrile is relatively acidic, with a p''K''a of 11 in water. This allows it to be used ...

) * 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 colorless solid. Preparation Benzimidazole is produced by condensation of o ...

) *

Tyrphostin A9 Malonoben (also known as tyrphostin A9, SF-6847, GCP5126, and AG-17) is an uncoupling agent/protonophore. As of 1974 when it was discovered, it was considered the most powerful agent of this type, with a potency over 1800 times that of 2,4-dinitr ...

(SF-6847) (AG17) * (+)-

usnic acid Usnic acid is a naturally occurring dibenzofuran derivative found in several lichen species with the formula C18H16O7. It was first isolated by German scientist W. Knop in 1844 and first synthesized between 1933-1937 by Curd and Robertson. Usnic a ...

XCT-790 XCT-790 is a potent and selective inverse agonist ligand (biochemistry), ligand of the estrogen-related receptor alpha (ERRα). Independent of its inhibition of ERRα, XCT-790 is a potent mitochondrial electron transport chain uncoupler. Mitochon ...

* mitoFluo (10-

-(3-hydroxy-6-oxo-xanthen-9-yl)benzoyl The hyphen-minus is the most commonly used type of hyphen, widely used in digital documents. It is the only character that looks like a minus sign or a dash in many character sets such as ASCII or on most keyboards, so it is also used as such. ...

xydecyl-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 ac ...

(Trichloro-2'-hydroxydiphenyl ether) * Pyrrolomycin C (produced by Genus Streptomyces) * Salicylic acid (if taken in extreme excess)

Pseudo-uncouplers

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

Biguanide Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea. Synthesis Biguanide can be obtained from ...

s *

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

* Calcimycin (

A23187 A23187 is a mobile ion-carrier that forms stable complexes with divalent cations ( ions with a charge of +2). A23187 is also known as Calcimycin, Calcium Ionophore, Antibiotic A23187 and Calcium Ionophore A23187. It is produced at fermentation of ...

) * Dodecyltriphenyl

phosphonium In polyatomic cations with the chemical formula (where R is a hydrogen or an alkyl, aryl, or halide group). These cations have tetrahedral structures. The salts are generally colorless or take the color of the anions. Types of phosphonium ...

(C₁₂TPP) *

Lasalocid Lasalocid is an antibacterial agent and a coccidiostat, which is produced by strains of ''Streptomyces lasaliensis''. It is the drug in the feed additives called Bovatec and Avatec. Lasalocid is able to make neutral complexes with monovalent and ...

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

linoleic acid Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. 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. ...

* MitoQ10 *

Nigericin Nigericin is an antibiotic derived from '' Streptomyces hygroscopicus''. Its isolation was described in the 1950s, and in 1968 the structure could be elucidated by X-ray crystallography. The structure and properties of nigericin are similar to th ...

* Picric acid (2,4,6-trinitrophenol) *

Sodium tetraphenylborate Sodium tetraphenylborate is the organic compound with the formula NaB(C6H5)4. It is a salt, wherein the anion consists of four phenyl rings bonded to boron. This white crystalline solid is used to prepare other tetraphenylborate salts, which are o ...

* SR4 (1,3-bis(dichlorophenyl)urea 13) *

Tetraphenylphosphonium chloride Tetraphenylphosphonium chloride is the chemical compound with the formula (C6H5)4PCl, abbreviated Ph4PCl or PPh4Cl. Tetraphenylphosphonium and especially tetraphenylarsonium salts were formerly of interest in gravimetric analysis of perchlorate an ...

Valinomycin Valinomycin is a naturally occurring dodecadepsipeptide used in the transport of potassium and as an antibiotic. Valinomycin is obtained from the cells of several ''Streptomyces'' species, '' S. fulvissimus'' being a notable one. It is a member o ...

Description

Classical uncouplers

Pseudo-uncouplers

See also

Notes

References

External links