Acetate-induced changes of adenine nucleotide levels in rat liver

Abstract

The changes in adenine nucleotide concentration induced by acetate were investigated in rat liver in situ and in isolated rat hepatocytes. Adenosine monophosphate (AMP) concentration increased approximately threefold with 15 minutes after intraperitoneal injection of sodium acetate. A small but significant decrease in adenosine triphosphate (ATP) concentration also occurred. Consequently, the ATP AMP ratio decreased from approximately 14 (the value found in control or sodium chloride-injected rats) to approximately 3 (the value found in sodium acetate-injected rats). Adenosine diphosphate (ADP) concentration increased slightly, but this was statistically nonsignificant. Total adenine nucleotide concentrations after acetate injection remained essentially the same as those in control rats. Adenylate energy charge decreased after acetate administration. No significant changes in nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) concentrations were found after sodium acetate injection. Similar patterns of changes in adenine nucleotide concentrations were found in isolated rat hepatocytes incubated in the presence of acetate. These data indicate that acetate, which appears in human blood either during hemodialysos with acetate-containing solution or after ethanol consumption, may alter energy equilibrium of adenine nucleotides in the liver. This is due to the conversion of ATP to AMP in the course of acetate to acetyl-coenzyme A (CoA) activation. It is therefore possible that accelerated ATP turnover in the liver may contribute both to the “intolerance to acetate” in patients subjected to dialysis with the sodium acetate-containing solution and to the pathogenesis of gout associated with excessive ethanol consumption.