Production of acetate in the liver and its utilization in peripheral tissues

In experimental rat liver perfusion we observed net production of free acet ate accompanied by accelerated ketogenesis with long-chain fatty acids. Mit ochondrial acetyl-CoA hydrolase, responsible for the production of free ace tate, was found to be inhibited by the free form of CoA in a competitive ma nner and activated by reduced nicotinamide adenine dinucleotide (NADH). The conditions under which the ketogenesis was accelerated favored activation of the hydrolase by dropping free CoA and elevating NADH levels. Free aceta te was barely metabolized in the liver because of low affinity, high K,, of acetyl coenzyme A (acetyl-CoA) synthetase for acetate. Therefore, infused ethanol was oxidized only to acetate, which was entirely excreted into the perfusate. The acetyl-CoA synthetase in the heart mitochondria was much low er in K, than it was in the liver, thus the heart mitochondria was capable of oxidizing free acetate as fast as other respiratory substrates, such as succinate. These results indicate that rat liver produces free acetate as a byproduct of ketogenesis and may supply free acetate, as in the case of ke tone bodies, to extrahepatic tissues as fuel. (C) 2001 Elsevier Science B.V . All rights reserved.