Studies of fatty acid oxidation. 7. The effects of fatty acids on the phosphate metabolism of slice and mitochondrial preparations of rat liver

Abstract

Fatty acids increase the respiratory activity of rat-liver and -kidney slices. At higher concentrations of the fatty acids, the initial stimulation of the rate of oxygen uptake is followed by a gradual decrease. The inhibitory effects increase with chain length, dodecanoate having the greatest effect. The inhibitions produced by higher acids were not as great. Fatty acids containing an odd number of carbon atoms were less effective inhibitors than those with one more or one less carbon atom. Decanoate (lmM) inhibited the oxidative phosphorylation associated with glutamate oxidation in rat-liver mitochondria by approximately 50%. It also decreased the P/O ratio associated with the oxidation of succinate and reduced cytochrome c. Decanoate and other fatty acids inhibited incorporation of [P32] phosphate into rat-liver slices at a concentration (1.34mM) which caused a stimulation of respiratory activity. [1-C14] Decanoate was oxidized to Cl4O2 and incorporated into lipids at these concentrations. The inhibitory effects of fatty acids are explained in terms of their effects on the enzyme systems involved in oxidative phosphorylation.