IDH2 and neoplasm: In contrast, while an excess of NAD + over NADH leads to IDH3-dependent oxidative decarboxylation, an increased concentration of NADH and a shortage of NAD + reroute αKG to glutamate through GDH This IDH2/IDH3 metabolic cycle also allows tumor cells to cope with mitochondrial oxidative stress generated by the disruption of the respiratory chain or induced by chemo- or radiotherapy [26, 48, 49].