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

From the ¹ From the Divisions of General Medicine and Endocrinology and Metabolism, Department of Medicine, University of Miami School of Medicine, Miami, Florida 33152

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.

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