Inhibition of Rat Liver Acetyl Coenzyme A Carboxylase by N6,O2′-Dibutyryl Cyclic Adenosine 3′:5′-Monophosphate in Vitro

Abstract

Abstract It has been established that hepatic lipogenesis in rats, mice, and chickens is inhibited by cyclic 3':5'-nucleotide monophosphates but their site of action has not previously been determined. Evidence is presented here that cyclic adenosine 3':5'-monophosphate (cAMP) and N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cAMP) inhibit the activity of acetyl coenzyme A carboxylase. Dibutyryl cAMP incubated with rat liver slices inhibited both lipogenesis and acetyl-CoA carboxylase activity to about the same extent. The amount of dibutyryl cAMP needed to inhibit acetyl-CoA carboxylase was in the same range as the amount needed to inhibit lipogenesis in rat and chicken liver slices. Inhibition of acetyl-CoA carboxylase by the addition of 1 mm dibutyryl cAMP to the enzyme assay reaction mixture was demonstrable even without preincubation with liver slices. It is concluded that a major portion of the inhibition of lipogenesis in rat liver by cAMP can be attributed to the inhibition of acetyl-CoA carboxylase.