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Uncoupler

{{Short description|Type of biological molecule}}

An uncoupler or uncoupling agent is a molecule that disrupts oxidative phosphorylation in prokaryotes and mitochondria or photophosphorylation in chloroplasts 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, but the proton-motive force is dissipated before the ATP synthase 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:{{cite journal |vauthors=Kessler RJ, Tyson CA, Green DE | year = 1976 | title = Mechanism of uncoupling in mitochondria: Uncouplers as ionophores for cycling cations and protons | journal = Proc Natl Acad Sci USA | volume = 73 | issue = 9 | pages = 3141–3145 | url = https://www.pnas.org/content/pnas/73/9/3141.full.pdf | jstor = 65688 | pmc = 430958 | doi=10.1073/pnas.73.9.3141 | pmid=9641| bibcode = 1976PNAS...73.3141K | doi-access = free }}

  1. the complete release of respiratory control
  2. the substitution of all coupled processes (ATP synthesis, transhydrogenation, reverse electron flow, active transport of cations, etc.) by a cyclic proton transport mediated by the uncoupler
  3. the elimination of all protonic and cationic gradients generated across the mitochondrial or prokaryotic membrane
  4. no discrimination in these actions between one coupling site and another
  5. 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:{{cite journal |vauthors=Childress ES, Alexopoulos SJ, Hoehn KS, Santos WL | year = 2018 | title = Small Molecule Mitochondrial Uncouplers and Their Therapeutic Potential | journal = J Med Chem | volume = 61 | issue = 11 | pages = 4641–4655 | doi = 10.1021/acs.jmedchem.7b01182 | pmid = 29156129}}

Pseudo-uncouplers

The following compounds are known to be pseudo-uncouplers:

See also

Notes

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References

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External links

  • {{MeshName|Uncoupling+Agents}}

Category:Ionophores

Category:Respiratory toxins

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