Abstract
The effects of octanoate and oleate were studied in the isolated fasted rat liver perfused without substrate and were compared with the effects of lactate. Measurements were made of hepatic adenine nucleotide content, formation of ketone bodies, urea and glucose and uptake of fatty acids, lactate and oxygen. Calculations of the Krebs cycle activity and the flux through the oxidation at C‐3 were carried out. Comparing the extra oxygen consumption with extra ATP needs after addition of the fatty acids or lactate, ADP: O ratios were estimated for fatty acid oxidation and lactate gluconeogenesis.1. Octanoate as well as oleate induced a net decrease in ATP and an increase in AMP content of the liver. Total adenine nucleotides were unaltered. ATP:ADP ratios were lowered while the adenylate kinase mass‐action ratio increased.2. The Krebs cycle activity was suppressed by both fatty acids and enhanced by lactate. Oxidation at C‐3 was strongly stimulated by the fatty acids and was unaffected by lactate.3. An apparent ADP:O ratio of 2.7 was obtained after lactate addition, indicating a tightly coupled oxidative phosphorylation for the liver preparations used. Octanoate and oleate gave extremely low ratios of near one and near zero respectively.4. Perfusion with oligomycin caused a severe drop in oxygen uptake by the liver, which was unaltered after addition of fatty acids. Oligomycin added after the fatty acids caused an immediate fall in oxygen uptake to the level observed with oligomycin alone. 2,4‐Dinitrophenol was able to stimulate the oligomycin‐depressed respiration, both in the absence and in the presence of fatty acids. These results indicate that under our experimental conditions the fatty acids had no uncoupling effect and that microsomal fatty acid oxidation had to be minimal.5. Incorporation of [3H]leucine into proteins in liver and medium remained unchanged after addition of fatty acids, indicating that the low apparent ADP:O ratios are not the result of an enhanced synthesis of proteins.6. The possible relationship between fatty acid transport, energy‐wasting futile cycles and the low apparent ADP:O ratios observed during fatty acid oxidation is discussed.
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