Inactivation of acetyl-coenzyme A carboxylase and fatty acid synthesis by N2, O2′-dibutyryl guanosine cyclic 3′,5′-monophosphate and N6, O2′-dibutyryl adenosine cyclic 3′,5′-monophosphate in isolated hepatocytes

Abstract

The effects of N 6, O 2′-dibutyryl adenosine cyclic 3′,5′-monophosphate and N 2, O 2′-dibutyryl guanosine cyclic 3′,5′-monophosphate on acetyl-CoA carboxylase and fatty acid synthesis were studied in isolated hepatocytes from mature rats (300–500 g). Both N 6, O 2′-dibutyryl adenosine cyclic 3′,5′-monophosphate and N 2, O 2′-dibutyryl guanosine cyclic 3′,5′-monophosphate caused the inactivation of hepatic acetyl-CoA carboxylase. The guanylic nucleotide was at least 10 times less potent than the adenosine cyclic 3′,5′monophosphate derivative in carboxylase inactivation. The inactivation of carboxylase by N 2,O 2′-dibutyryl guanosine cyclic 3′,5′-monophosphate correlated with a decrease in the incorporation of [1- 14C]acetate into fatty acids and was accompanied by an increase in the incorporation of [ 32P]phosphate into the enzyme. The inactivation of the hepatic acetyl-CoA carboxylase by either N 6,O 2′-dibutyryl adenosine cyclic 3′,5′-monophosphate or N 2,O 2′-dibutyryl guanosine cyclic 3′,5′-monophosphate required calcium.