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So, during DR, NAD + -dependent PDC and citric acid cycle dehydrogenases IDH3, α-ketoglutarate dehydrogenase (OGDH), and MDH2 may be slightly inhibited, leading to decreased flux through the MAS, even though MDH2 is not the rate-limiting step of the MAS, contributing to the reduction in the brain cytoplasmic [NAD + ]/[NADH] observed during DR