Sorbitol antiketogenesis and the dehydrogenation and oxidation of fatty acids

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Abstract
Spontaneous ketogenesis was demonstrated in liver homogenates of fasted rats and was found independent of added co-factors. Such spontaneous ketogenesis and the formation of acetoacetate from added substrates in homogenates are not affected by added sorbitol even when the latter is being rapidly oxidized. For the activation of octanoate oxidation in washed mitochondria suspensions coenzyme I (Col) can replace adenosinetriphosphate (ATP). When livers from fasted rats are used for the prepn. of mitochondria, the activating effects of ATP and CoI are additive. The oxidation of octanoate with acetoacetate formation in washed mitochondria suspensions is unaffected by the simultaneous dehydrogenation of sorbitol by purified dehydro-genase prepns. The results are unchanged by the presence or absence of CoI and of Co I_cytochrome c reductase. In the presence of methylene blue and ATP, saturated fatty acids (C4 to C18), undecylenate and oleate are dehydrogenated anaero. bically in suspensions of the washed particles from rat liver homogenates. No other co-factors are required; adenosine_3_ phosphate cannot replace ATP. The anaerobic fatty acid dehy-drogenase system is probably located in the mitochondria. It is not inhibited by 0.005 [image] HCN or 0.01 [image] malonate. The significance of these results for theories of the mechanism of sorbitol antiketogenesis is discussed.