Carboxyatractylate inhibits the uncoupling effect of free fatty acids.
The ATP/ADP-antiporter inhibitors and ADP decrease the palmitate-induced stimulation of the mitochondrial respiration in the controlled state. The degree of inhibition decreases in the order: carboxyatractylate greater than bongkrekic acid, palmitoyl-CoA, ADP greater than atractylate. GDP is ineffective. The inhibiting concentration of carboxyatractylate coincides with this arresting the state 3 respiration. Carboxyatractylate inhibition decreases when the palmitate concentration increases. Stimulation of controlled respiration by FCCP or gramicidin D at any concentration of these uncouplers is carboxyatractylate-resistant, whereas that by low concentrations of DNP is partially suppressed by carboxyatractylate. These data together with observations that palmitate does not increase H+ conductance in bilayer phospholipid membranes and in cytochrome oxidase-asolectin proteoliposomes indicate that the ATP/ADP-antiporter is somehow involved in the uncoupling by low concentrations of fatty acids (or DNP), whereas that by FCCP and gramicidin D is due to their effect on the phospholipid bilayer. It is suggested that the antiporter facilitates translocation of palmitate anion across the mitochondrial membrane.
Andreyev AYu
A.N. Belozersky Laboratory of Molecular Biology and Bioorganic Chemistry, Moscow State University, USSR.
Bondareva
T O
TO
Dedukhova
V I
VI
Mokhova
E N
EN
Skulachev
V P
VP
Volkov
N I
NI
D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D051381:Rats; D014475:Uncoupling Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004140:Dinitrophenols; D005230:Fatty Acids, Nonesterified; D006027:Glycosides; D010169:Palmitic Acids; D014475:Uncoupling Agents; D001278:Atractyloside; D019308:Palmitic Acid; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C003853:carboxyatractyloside