Ketone-body metabolism in hyperthyroid rats: Reduced activity of d-3-hydroxybutyrate dehydrogenase in both liver and heart and of succinyl coenzyme A: 3-Oxoacid coenzyme A-transferase in heart

Abstract The specific activity of d -3-hydroxybutyrate dehydrogenase is reduced by about a third in liver and heart mitochondria of hyperthyroid rats. State 3 respiration is also reduced in isolated mitochondria from the same animals when dl -3-hydroxybutyrate is the substrate. Determination of the kinetic parameters of the membrane-bound d -3-hydroxybutyrate dehydrogenase in liver of hyperthyroid rats reveals a decreased in maximal velocity ( V max ). The Michaelis and dissociation constants of NAD + and d -3-hydroxybutyrate are also significantly influenced, thus indicating that both the affinity and the binding of this enzyme toward its substrates are affected. In hyperthyroid rats a significant ketone-body increase is found in both liver and heart: in blood, an almost doubled concentration can be measured. At the same time, in heart mitochondria of these animals the activity of succinyl-coenzyme A: 3-oxoacid coenzyme A-transferase is significantly reduced. The decrease in both d -3-hydroxybutyrate dehydrogenase and 3-oxoacid coenzyme A-transferase associated with the increase in ketone bodies supports the suggestion that there is a lower utilization of these compounds by peripheral tissues. In the blood of hyperthyroid rats a higher d -3-hydroxybutyrate/acteoacetate ratio is also found, probably resulting from a selective utilization of the two compounds in this pathological state.