Hiromi Yamashita، نويسنده , , Takao Kaneyuki، نويسنده , , Kunio Tagawa، نويسنده ,

1601770

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

12299

In experimental rat liver perfusion we observed net production of free acetate accompanied by accelerated ketogenesis with long-chain fatty acids. Mitochondrial acetyl-CoA hydrolase, responsible for the production of free acetate, was found to be inhibited by the free form of CoA in a competitive manner 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 acetate was barely metabolized in the liver because of low affinity, high Km, 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 lower in Km 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 ketone bodies, to extrahepatic tissues as fuel.

79

fatty acid , L-Oxidation , acetate metabolism , ketogenesis , Acetyl coenzyme A hydrolase , Acetyl coenzyme A synthetase

Studia Iranica

87

87