Dihydrolipoic acid activates oligomycin-sensitive thiol groups and increases ATP synthesis in mitochondria.
Investigations with dihydrolipoic acid in rat heart mitochondria and mitoplasts reveal an activation of ATP-synthase up to 45%, whereas ATPase activities decrease by 36%. In parallel with an increase in ATP synthesis oligomycin-sensitive mitochondrial -SH groups are activated at 2-4 nmol dihydrolipoic acid/mg protein. ATPase activation by the uncouplers carbonylcyanide-p-trifluoromethoxyphenylhydrazone and oleate is diminished by dihydrolipoic acid, and ATP synthesis depressed by oleate is partially restored. No such efficiency of dihydrolipoic acid is seen with palmitate-induced ATPase activation or decrease of ATP synthesis. This indicates different interference of oleate and palmitate with mitochondria. In addition to its known coenzymatic properties dihydrolipoic acid may act as a substitute for coenzyme A, thereby diminishing the uncoupling efficiency of oleate. Furthermore, dihydrolipoic acid is a very potent antioxidant, shifting the -SH-S-S- equilibrium in mitochondria to the reduced state and improving the energetic state of cells.
Zimmer
G
G
Gustav-Embden-Zentrum der Biologischen Chemie, Universität Frankfurt, Germany.
Mainka
L
L
Krüger
E
E
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D009829:Oleic Acids; D009840:Oligomycins; D010169:Palmitic Acids; D013438:Sulfhydryl Compounds; D001278:Atractyloside; D019301:Oleic Acid; D019308:Palmitic Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C003853:carboxyatractyloside