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. Author manuscript; available in PMC: 2018 Sep 21.
Published in final edited form as: Cell Chem Biol. 2017 Sep 21;24(9):1161–1180. doi: 10.1016/j.chembiol.2017.08.028

Figure 5. TCA Cycle.

Figure 5

Pyruvate produced by glycolysis can be metabolized by the TCA cycle. Pyruvate is oxidized via pyruvate dehydrogenase (PDH) to the two-carbon unit acetyl-CoA, and subsequently combined with the four-carbon oxaloacetate to generate citrate. The cycle regenerates oxaloacetate while generating precursors that are important for biosynthetic processes including heme and fatty acid synthesis. When molecules are removed from the TCA cycle to feed these pathways, TCA intermediates must be replenished in a process termed anaplerosis. Pyruvate can serve as an anaplerotic substrate when converted to oxaloacetate by the enzyme pyruvate carboxylase (PC). Glutaminolysis, the conversion of glutamine to glutamate via glutaminase (GLS), can also support anaplerosis via production of α-ketoglutarate. PDH activity is inhibited by the lipoic acid derivative CPI-613 and GLS activity is inhibited by CB-839.