By using [1-14C]butyrate, the fluxes of butyrate to acetate and fatty acids were measured in rat hepatocytes. Both fluxes were inhibited to a similar extent by (-)-hydroxycitrate, with no significant effect on butyrate uptake. These results indicate that acetate formation takes place in the cytoplasm, presumably via ATP-stimulated acetyl-CoA hydrolase. Since acetate formation occurred despite a net uptake of acetate, the results are also consistent with the operation of a substrate cycle between acetate and acetyl-CoA, recently proposed by other workers, and suggest that this cycle is cytoplasmic.

SUMMARYAcetyl-CoA hydrolase which is stimulated by adenosine-5′-triphosphate is present in the cytoplasm of ovine liver and, unlike in certain others species, is not inactivated by cold. It is suggested that this enzyme is involved in a substrate cycle between acetate and acetyl-CoA. The heat produced as a result of such cycling may be as much as 2·5% of basal heat production and may be partly responsible for the increased heat increment that often follows the ingestion of diets that provide large quantities of acetate.