SUBCELLULAR DISTRIBUTION OF ISOCITRATE DEHYDROGENASES IN NEONATAL AND ADULT MOUSE BRAIN

Abstract— The activity and subcellular distribution of NADP- and NAD-isocitrate de-hydrogenases (ICDH) (EC 1.1.1.42 and 1.1.1.41, respectively) in brains of adult and newborn mice have been determined. In the adult, NAD-ICDH activity in whole brain homogeantes was 1–17 mol/kg wet wt of brain/h (MKH), whereas the NADP-ICDH activity was 0.223 MKH. In the newborn, the activity of the NAD-dependent enzyme was only 0.246 MKH, whereas the NADP-dependent enzyme activity was 1.23 MKH. At both ages, 66 per cent of the NADP-ICDH activity was in the cytosol, less than 10 per cent was in the purified mitochondrial fraction and the remainder was in the crude synaptosomal fraction. Less than 10 per cent of the NAD-ICDH activity was in the cytosol in both the newborn and adult, whereas 50 per cent was in the purified mitochondrial fraction. The crude synaptosomal fraction from the newborn and adult brains contained 28 and 22 per cent, respectively, of the total NAD-ICDH activity. The activities of these enzymes in the cytosol and mitochondria were compared with those of succinate dehydrogenase and with three other enzymes which utilize the product, 2-oxoglutarate, as substrate. The relationship of the isocitrate dehydrogenases to the metabolism of adult and newborn brain is discussed.