Publisher Summary This chapter discusses the occurrence of the enzymes in microorganisms, plants, and animals as well as their distribution in animal tissues. The DPN-linked isocitrate dehydrogenase activity was first detected and separated from the corresponding TPN-linked enzyme in yeast. Intramitochondrial isocitrate oxidation is controlled by factors relating to the energy-linked electron transport system. The DPN-linked enzyme occurs in a number of other microorganisms, such as, Aspergillus niger, Neurospora crassa, Acetobacter suboxidans, Blastocladiella emersomi, and Thiobacillus thiooxidans. In contrast to the corresponding TPN enzyme, the DPN isocitrate dehydrogenases from heart and yeast do not catalyze the decarboxylation or reduction by reduced pyridine nucleotide of oxalosuccinate. In the presence of the heart enzyme, the hydrogen atom from the α -position of threo -D S -isocitrate is transferred to the α side of the nicotinamide ring of DPN. In the presence of relatively low concentrations of isocitrate and without ADP, the enzyme is maximally active in the rather narrow range of pH 6.5–6.9.