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. Author manuscript; available in PMC: 2010 Jul 15.
Published in final edited form as: Free Radic Biol Med. 2009 Apr 10;47(2):115–127. doi: 10.1016/j.freeradbiomed.2009.04.010

Fig. 7. The current model for the relationship between cancer metabolic defects and epigenetic processes.

Fig. 7

(A) Tumor cells increase their production of GSH to counter mitochondrially derived oxidants such as O2•− and H2O2. To sustain GSH production, cancer cells divert metabolites away from the methionine cycle into the transsulfuration pathway, resulting in decreased SAM production. (B) Aberrant production of oxidants creates an atypical redox state by decreasing the GSH/GSSG ratio which affects the activities of SAM synthetases, DNMTs and HMTs. (C) The increased Glc (glucose) consumption of the Warburg effect decreases the NAD+/NADH ratio and produces Pyr (pyruvate). Decreasing this ratio creates an environment that inhibits the activity of sirtuins, and liberates genes from their negative regulation. (D) Oxidation of glutamine (Gln), and dysfunctional electron transport, alters the flow of α-KG (α-ketoglutarate) and Suc (succinate) metabolites within the Krebs cycle. These metabolites can then influence transcription in the nucleus by affecting the activity of KDMs (lysine demethylases).