Popis: |
Fatty acid oxidation was studied in the presence or absence of adenosine triphosphate with the use of sodium octanoate-1-14C as substrate. In the absence of ATP, fatty acid oxidation proceeded at a rate 5 to 30% of that obtained in the presence of optimal ATP. The rate of oxidation was partially inhibited by the uncoupling agents dinitrophenol, Dicumarol, or arsenate, completely inhibited by cyanide or antimycin A, and stimulated by oligomycin or azide. The dinitrophenol inhibition was not reversed by oligomycin, although the arsenate inhibition was reversed by oligomycin. Fatty acid oxidation was only slightly inhibited by arsenite, suggesting that substrate level phosphorylation makes only a small contribution to fatty acid activation. In the presence of ATP or ADP, fatty acid oxidation was inhibited both by uncoupling agents and by oligomycin. The oligomycin inhibition was reversed by increasing concentrations of ATP. After preincubation with glucose and hexokinase, the rate of fatty acid oxidation in the absence of ATP was only slightly reduced. Addition of oligomycin reversed this inhibition. Fluoride ion inhibited fatty acid oxidation in the presence of ATP or ADP but had no effect on the oxidative rate in the absence of nucleotides. These results indicate that fatty acids are activated in brain mitochondria by two different mechanisms: (a) an ATP-linked reaction which used primarily the ATP produced during respiration and (b) a system involving high energy intermediates of oxidative phosphorylation. |