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α-KG, 2-HG, and Epigenetic Control. Under healthy conditions (upper panel), the cytosol and the mitochondria IDH enzymes produce the metabolite α-KG which is utilized as a cofactor in DNA demethylation and histone deacetylation reactions. In cancer conditions (lower panel), the IDH enzymes instead produce the oncometabolite 2-HG, an α-KG analog which competitively inhibits DNA demethylases and histone deacetylases. Relationship between altered metabolism and an altered epigenome.
