Evidence that the production of acetate in rat hepatocytes is a predominantly cytoplasmic process.

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.