![]() ![]() This product is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone, demethylases, prolyl-4-hydroxylase and the TET enzymes family (Ten-Eleven Translocation-2), resulting in genome-wide alternations in histones and DNA methylation. Two distinct alterations are caused by tumor-derived mutations in IDH1 or IDH2: loss of its normal catalytic activity during the production of α-ketoglutarate (α-KG) and the gain of catalytic activity to produce 2-hydroxygulatrate (2-HG). The DH1 and IDH2 genes are mutated in > 75% of different malignant diseases. In the Krebs cycle (the citric cycle), IDH1 and IDH2 are NADP+-dependent enzymes that normally catalyze the inter-conversion of D-isocitrate and alpha-ketoglutarate (α-KG). In aerobic glucose metabolism, the oxidation of citric acid uses ADP and Mg²+, which will increase the speed of reaction: Iso-citric acid + NADP (NAD) - isocitrate dehydrogenase (IDH) = alpha-ketoglutaric acid.
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