The oxidation of long-chain unsaturated fatty acids by isolated rat liver mitochondria as a function of substrate concentration.
1. The oxidation of linoleate by rat-liver mitochondria has been studied as a function of substrate concentration. The oxidation of other long-chain unsaturated fatty acids shows similar characteristics. 2. At low concentrations, linoleate is readily oxidized in the absence of carnitine. Its rate of activation by the intramitochondrial acyl-CoA synthetase (EC 6.2.1.2) and subsequent oxidation is limited by the availability of intra-mitochondrial ATP. 3. A gradual increase of the linoleate concentration leads to (i) a strong depression of the rate of linoleate oxidation, and (ii) uncoupling of respiratory-chain phosphorylation together with induction of a mitochondrial ATPase activity. At still higher linoleate concentrations this ATPase activity is lowered rather than further stimulated and, concomitantly, the rate of linoleate oxidation increases again. 4. Evidence is presented that the inhibition by linoleate of the ATPase activity occurs at the level of the ATPase complex itself. This oligomycin-like effect of linoleate allows intramitochondrial linoleate activation to take place at the expense of ATP derived from substrate-level phosphorylation. 5. At very high concentrations of linoleate, its detergent action predominates and causes a complete inhibition of respiration as well as an extensive stimulation of an oligomycin-insensitive, Mg2+-dependent ATPase activity. 6. Measurement of the binding of radioactively labelled linoleate by isolated mitochondria shows that, at a given ratio of linoleate to mitochondrial protein, the ratio of bound to added linoleate is dependent on the concentration of the mitochondria.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008041:Linoleic Acids / Q000378:metabolism; D008823:Micelles; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats
D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008823:Micelles; D010169:Palmitic Acids; D000251:Adenosine Triphosphatases; D003066:Coenzyme A Ligases