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. Author manuscript; available in PMC: 2019 Aug 1.
Published in final edited form as: Biochim Biophys Acta Rev Cancer. 2018 Apr 25;1870(1):2–14. doi: 10.1016/j.bbcan.2018.04.009

Figure 1. Oncometabolites inhibit α-KG-dependent dioxygenases.

Figure 1

α-KG is required for the function of a family of dioxygenase enzymes including histone demethylases, which remove methyl groups from lysine residues in histone proteins; 5-methylcytosine hydroxylases, which initiate demethylation of cytosine bases; and prolyl hydroxylases, which hydroxylate proline residues in proteins such as the α subunits of hypoxia inducible factors (HIFs). These dioxygenases can be inhibited by high levels of other dicarboxylic acids, which compete with α-KG. Dicarboxylic acids demonstrated to inhibit dioxygenases include D-HG (a product of mutant IDH1/2) and fumarate and succinate, which accumulate due to loss-of-function mutations in FH and SDH, respectively.