Evidence for Regulation of Cholesterol and Fatty Acid Synthesis in Liver by Cyclic Adenosine 3′,5′-Monophosphate

Abstract

Abstract Cyclic adenosine 3',5'-monophosphate at 5 x 10-5 m decreased the incorporation of [2-14C]acetate into fatty acid (36 ± 5%) in rat liver slices. Concentrations of cyclic adenosine 3',5'-monophosphate of 5 x 10-3 m and higher decreased cholesterol synthesis by more than 80%. The dibutyryl analog of the nucleotide produced a similar significant inhibition of fatty acid synthesis and cholesterol synthesis, but at concentrations up to 100-fold less. Metabolic evolution of CO2 was not significantly depressed at any concentration of either nucleotide. The data indicate that cyclic adenosine 3',5'-monophosphate may be involved in regulating acetyl-CoA incorporation into de novo fatty acid and cholesterol in a specific manner in mammalian liver.