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The promiscuity of LDHA, MDH, and PHGDH and the metabolism of 2-HG. 2-HG derives from the promiscuity of LDHA, MDH1, and PHGDH in the cytoplasm and MDH2 in the mitochondria. Mutations of IDH1 and IDH2 endow them the neomorphic enzyme activity to convert α-KG to D-2HG. L-2HG and D-2HG are removed by L2HGDH and D2HGDH from the mitochondria, respectively. LDHA, lactate dehydrogenase A; MDH, malate dehydrogenase; 2-HG, 2-hydroxyglutarate.
