Activation of hepatic branched chain alpha-keto acid dehydrogenase by a skeletal muscle factor.

Abstract

These experiments were designed to determine whether there are tissue factors which affect the activity of branched chain alpha-keto acid (BCKA) dehydrogenase in the mitochondria of the same or different tissues. The activity of BCKA dehydrogenase was increased by the addition of the cytoplasmic fraction of the gastro-cnemius muscle to liver mitochondria. The specificity of the effect of the muscle factor was established by the fact that it only increased the BCKA dehydrogenase activity in liver mitochondria. The activity of this enzyme in mitochondria from skeletal muscle, heart, kidney, or brain was either not affected or inhibited by the muscle factor. Muscle factor also increased the activity of alpha-ketoglutarate dehydrogenase but decreased that of pyruvate dehydrogenase in liver mitochondria. This factor was found in a variety of skeletal muscles but not in smooth muscle such as uterus. A factor similar to that of muscle was not found in liver or kidney cytoplasm but was detected in plasma. There were similarities between the effects of muscle and plasma factors on the BCKA dehydrogenase activity in liver, kidney, heart, and skeletal muscle mitochondria. Studies concerning the properties and partial characterization of this factor revealed that it (a) is nondialyzable, (b) is a protein, (c) is heat labile, and (d) increases the activity of BCKA dehydrogenase by increasing the Vmax without a change in the apparent Km.