Inhibition of cardiac NADP-linked isocitrate dehydrogenase by adriamycin

The inhibitory action of adriamycin against two NADP-linked dehydrogenases of rat heart was investigated. In heart muscle, isocitrate dehydrogenase activity is particularly high, whereas that of glucose-6-phosphate dehydrogenase is very low. Adriamycin inhibited the activity of both mitochondrial and cytoplasmic isocitrate dehydrogenase dose-dependently, but had no effect on glucose-6-phosphate dehydrogenase. The inhibiton by adriamycin was noncompetitive. Pre-incubation of the crude cardiac enzyme preparations with adriamycin enhanced the inhibition of isocitrate dehydrogenase time-dependently for 45 minutes.