Active and inactive forms of pyruvate dehydrogenase in rat heart and kidney: Effect of diabetes, fasting, and refeeding on pyruvate dehydrogenase interconversion

Abstract

Pyruvate dehydrogenase (PDH) activity was measured in homogenates from rat heart and kidney. The activity before addition of Mg 2+ to homogenate was used as a measure of the active form (PDH a) originally present. The activity after incubation in presence of Mg 2+ is then representative for the total PDH activity present in the tissue. This assay is justified if it is assumed that Mg 2+ stimulates PDH phosphatase which catalyzes conversion of the inactive (PDH b) to the active form of PDH. Marked changes in the amount of PDH a without significant changes in total PDH activity were observed in heart and kidney from rats subjected to a variety of metabolic conditions and treatments: on fasting PDH a levels decreased to less than 15% of total activity. On refeeding glucose or fructose PDH a levels rose to normal (70% of total activity). Similarly PDH a levels fell to less than 15% of total activity in heart and kidney of alloxan diabetic rats on withdrawal of insulin and were likewise restored to normal on insulin treatment. Treatment of fasted rats with nicotinic acid—an antilipolytic agent—brought back to normal the PDH a levels lowered by fasting. PDH a activity but not total PDH activity was inversely related to serum free fatty acid levels. These and other findings point to a possible role of the PDH interconversion for the regulation of pyruvate metabolism. The observations discussed in this report could explain the well known inhibition of pyruvate oxidation in diabetes and in other metabolic conditions where fatty acids are preferentially oxidized.