Enzymes Involved in Ketone Utilization in Different Types of Muscle: Adaptation to Exercise

Activity levels of the enzymes involved in ketone utilization were compared in heart, fast‐twitch red, slow‐twitch red, and fast‐twitch white types of muscles in rats. 3‐Hydroxybutyrate dehydrogenase, 3‐ketoacid CoA‐transferase, and acetoacetyl‐CoA thiolase activities were lowest in white muscle, higher in slow red than in fast red muscle, and highest in the heart. The large differences between the four muscle types in the levels of these enzymes reflects differences in both mitochondrial content and composition. Differences in composition were evidenced by large dissimilarities between the different muscle types in the ratios of the activities of the enzymes of ketone oxidation to each other and to citrate synthase and cytochrome c. Of particular interest is the finding that, despite the fact that in the rat slow red muscle has a lower content of mitochondria than fast red muscle, 3‐hydroxybutyrate dehydrogenase activity is 140% higher and 3‐ketoacid CoA‐transferase is 70% higher in slow red than in fast red muscle. A 14‐week‐long program of treadmill running induced increases in the levels of ketone utilization enzymes in all three types of skeletal muscle but not in heart; 3‐hydroxybutyrate dehydrogenase became measurable, though at very low levels, in white muscle; increased 2.6‐fold in slow red muscle, and 6‐fold in fast red muscle. 3‐Ketoacid CoA‐transferase increased 2‐fold in both fast red and white types of muscle, but only 26% in slow red muscle. Acetoacetyl‐CoA thiolase activity increased 40–45% in all three types of skeletal muscle. In contrast, citrate synthase and cytochrome c increased approximately 2‐fold in all three types of skeletal muscle. These adaptive changes tend to make skeletal muscles more like heart muscle in their enzyme patterns and may help to explain why physically trained, as compared to untrained, individuals do not develop post‐exercise ketosis.