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Uncoupler

From Wikipedia, the free encyclopedia
Type of biological molecule

Anuncoupler oruncoupling agent is a molecule that disruptsoxidative phosphorylation inprokaryotes andmitochondria orphotophosphorylation inchloroplasts andcyanobacteria by dissociating the reactions of ATP synthesis from theelectron transport chain. The result is that the cell or mitochondrion expends energy to generate aproton-motive force, but the proton-motive force is dissipated before theATP synthase can recapture this energy and use it to makeATP. 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

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Classical uncouplers have five properties:[1]

  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 allprotonic 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.[1]

Classical uncouplers

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The following compounds are known to be classical uncouplers:[1][2]

Pseudo-uncouplers

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The following compounds are known to be pseudo-uncouplers:[1]

See also

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Notes

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  1. ^Not to be confused with the recreation drug,phencyclidine.

References

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  1. ^abcdKessler RJ, Tyson CA, Green DE (1976)."Mechanism of uncoupling in mitochondria: Uncouplers as ionophores for cycling cations and protons"(PDF).Proc Natl Acad Sci USA.73 (9):3141–3145.Bibcode:1976PNAS...73.3141K.doi:10.1073/pnas.73.9.3141.JSTOR 65688.PMC 430958.PMID 9641.
  2. ^Childress ES, Alexopoulos SJ, Hoehn KS, Santos WL (2018). "Small Molecule Mitochondrial Uncouplers and Their Therapeutic Potential".J Med Chem.61 (11):4641–4655.doi:10.1021/acs.jmedchem.7b01182.PMID 29156129.
  3. ^"California Poison Control System: Salicylates". Archived fromthe original on 2014-08-02.

External links

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