Active and Inactive Forms of Pyruvate Dehydrogenase in Rat Liver

Active form and total activity of pyruvate dehydrogenase were measured in rat liver homogenates. The activity obtained immediately after homogenization was considered to represent the active form, i.e. dephospho pyruvate dehydrogenase, originally present in the liver. Enzyme activity found after incubation of the homogenate with Mg 2+ and partially purified pyruvate dehydrogenase phosphatase from pig heart, whereby inactive dehydrogenase is dephosphorylated to give the active form, was regarded as total pyruvate dehydrogenase activity. In the livers from normal fed rats, the active form accounts for only one sixth of total pyruvate dehydrogenase activity. This differs from other tissues such as heart muscle, kidney, brain and adipose tissue where about two thirds of total pyruvate dehydrogenase are present as the active form (Wieland et al. , 1971; Siess et al. , 1971). To elucidate the possible role of pyruvate dehydrogenase interconversion in the regulation of pyruvate metabolism in liver, the activity of active and total pyruvate dehydrogenase were determined in livers of rats subjected to various metabolic conditions. After fasting and refeeding with glucose as well as after treatment with nicotinic acid or insulin there were significant changes of active dehydrogenase activity without gross alterations of total activity. In general, metabolic states associated with decreased plasma fatty acids resulted in an increase of active pyruvate dehydrogenase whereas a rise in plasma fatty acids led to a lowering. It is concluded that in liver, similar to heart muscle and kidney (Wieland et al. , 1971), fatty acids play an important role in the control of pyruvate dehydrogenase interconversion. The significance of this mechanism for the regulation of pyruvate metabolism in liver relative to the feedback control of pyruvate dehydrogenase by acetyl‐CoA is discussed.