title: Carboxyatractylate inhibits the uncoupling effect of free fatty acids.
abstract: 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.
authors.affiliation: A.N. Belozersky Laboratory of Molecular Biology and Bioorganic Chemistry, Moscow State University, USSR.
authors.lastname: Andreyev AYu
authors.forename: T O
authors.initials: TO
authors.lastname: Bondareva
authors.forename: V I
authors.initials: VI
authors.lastname: Dedukhova
authors.forename: E N
authors.initials: EN
authors.lastname: Mokhova
authors.forename: V P
authors.initials: VP
authors.lastname: Skulachev
authors.forename: N I
authors.initials: NI
authors.lastname: Volkov
mesh_terms: 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*
chemical_list: 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