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Science Forum Index » Life Extension Forum » BHT / Uncoupling at low concentrations...
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| jc101... |
 Posted: Mon Jun 09, 2008 11:49 am |
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Mitochondrial uncouplers with an extraordinary dynamic range.Lou PH,
Hansen BS, Olsen PH, Tullin S, Murphy MP, Brand MD.
MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
We have discovered that some weak uncouplers (typified by butylated
hydroxytoluene) have a dynamic range of more than 10(6) in vitro: the
concentration giving measurable uncoupling is less than one millionth
of the concentration causing full uncoupling. They achieve this
through a high-affinity interaction with the mitochondrial adenine
nucleotide translocase that causes significant but limited uncoupling
at extremely low uncoupler concentrations, together with more
conventional uncoupling at much higher concentrations. Uncoupling at
the translocase is not by a conventional weak acid/anion cycling
mechanism since it is also caused by substituted triphenylphosphonium
molecules, which are not anionic and cannot protonate. Covalent
attachment of the uncoupler to a mitochondrially targeted hydrophobic
cation sensitizes it to membrane potential, giving a small additional
effect. The wide dynamic range of these uncouplers in isolated
mitochondria and intact cells reveals a novel allosteric activation of
proton transport through the adenine nucleotide translocase and
provides a promising starting point for designing safer uncouplers for
obesity therapy.
PMID: 17608618
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17608618
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