Figure 2.
Dioxygenases in sensing metabolic intermediates and epigenetic regulation. (A) Schematics of α-KG metabolism and TCA cycle. The mutant isocitrate dehydrogenase (IDH) (indicated with a star) may decrease α-KG and generate a new oncometabolite 2-hydroxylglutarate (2-HG). (B) A proposed role of dioxygenases in metabolite sensing and epigenetic modifications. Using α-KG as a key substrate, dioxygenases is involved in HIFα hydroxylation, DNA demethylation, and histone demethylation. All processes are inhibited by normal metabolites, such as succinate and fumarate, as well as oncometabolite 2-HG. α-KG, α-ketoglutarate; GDH, glutamate dehydrogenase; SDH, succinate dehydrogenase; FH, fumarase; TET, ten-eleven translocation; KDM, lysine demethylase; PHD, prolyl hydroxylase domain protein.