An anti-anabolic role of adenosine 3',5'-cyclic monophosphate in the control of liver metabolism. a hypothetical mechanism for gluconeogenesis

Abstract

1. 1. It is shown that in rat liver slices cyclic AMP caused a co-ordinated inhibition of protein, fatty acid, and cholesterol synthesis (anti-anabolic) from several radioactive precursors. 2. 2. The inhibition of cholesterol and fatty acid synthesis was due to a genuine decrease in the activity of the biosynthetic pathway. 3. 3. Under conditions when the anti-anabolic effect was obtained, the incorporation of [ 14CJbicarbonate into glucose was increased, confirming that cyclic AMP favours glyconeogencsis. 4. 4. The mechanism by which cyclic AMP produced these effects was studied further by the use of cell-free preparations from rat liver. Cyclic AMP was shown to inhibit protein synthesis in a postmitochondrial supernatant. This inhibition only occurred in the presence of an excess of the postmicrosomal supernatant fraction. These results are discussed on the basis that cyclic AMP might interact with a component in the posticrosomal fraction capable of modifying the activity of the protein synthetic machinery. 5. 5. Examples are provided to suggest that this anti-anabolic effect of cyclic AMP may operate in vivo.