Interconversion of Pyruvate Dehydrogenase in the Isolated Perfused Rat Liver

TLDR: It is shown that fatty acid oxidation is required for the inactivation of pyruvate dehydrogenase by interconversion of the active to the inactive form by fatty acids in the regulation of pyrivate dehydration by means of fatty acids and fatty acids.

Abstract: Active form and total activity of pyruvate dehydrogenase were measured in homogenates prepared from tissue samples obtained from the isolated rat liver during perfusion. In the absence of substrate, the active portion accounted for about 20% of total activity in livers from fed rats, whereas only about 10% were found to be active in livers from starved rats. These activities remained rather constant during a perfusion period of 120 min. Addition of 10 mM pyruvate to the perfusion medium resulted in an immediate, three-fold increase of the active pyruvate dehydrogenase. A similar effect was exerted by 20 mM fructose, which is known to be rapidly converted to pyruvate in liver. 10 mM lactate led to a considerably smaller increase of pyruvate dehydrogenase activity as compared to the effects obtained with pyruvate or fructose. Total activities of the enzyme did not change significantly during perfusion. If the activities of active pyruvate dehydrogenase from livers perfused with and without substrate were plotted against medium pyruvate concentrations an exponential correlation could be observed. Addition of 2 mM oleate abolished the effects of fructose or pyruvate on the formation of active pyruvate dehydrogenase. The simultaneous addition of d-(+)-decanoylcarnitine inhibited the action of oleate, indicating that fatty acid oxidation is required for the inactivation of pyruvate dehydrogenase by interconversion of the active to the inactive form. The possible physiological significance of pyruvate and fatty acids in the regulation of pyruvate dehydrogenase interconversion is discussed.