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. Author manuscript; available in PMC: 2013 Jul 3.
Published in final edited form as: Cell Metab. 2012 Jul 3;16(1):9–17. doi: 10.1016/j.cmet.2012.06.001

Figure 3. Crosstalk between metabolism and epigenetics.

Figure 3

As glucose enters the glycolytic pathway, a minor portion is branched to hexosamine biosynthetic pathway to produce GlcNAc which can be used as substrate for histone GlcNAcylation by OGT. Flux through glycolysis determines the NAD+/NADH ratio which is important for the activities of sirtuin histone deacetylases. Several TCA cycle intermediate can be exported out of mitochondria including citrate and αKG. Cytosolic citrate is converted to acetyl-CoA which is used as a donor for HAT-mediated histone acetylation. αKG is used as co-factors for histone and DNA demethylation reactions by JHDM and TET, respectively. The substrate for HMT and DNMT is SAM which is synthesized from essential amino acid methionine. Finally, a low ATP/AMP ratio can activate AMPK, a kinase that phosphorylates histones.