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. Author manuscript; available in PMC: 2020 Jun 10.

Published in final edited form as: Trends Analyt Chem. 2018 Nov 24;120:115322. doi: 10.1016/j.trac.2018.11.020

Figure 5. — The diagram depicts ¹³C tracing from ¹³C₆-glucose () or ¹³C/¹⁵N tracing from ¹³C₅,¹⁵N₂ glutamine () to the synthesis of nucleotides and effectors (dark red text) involved in epigenetic modifications, including αketoglutarate (αKG), 2-hydroxyglutarate (2HG), succinate, and fumarate. IDH1/2 mutants produce the histone demethylation inhibitor 2HG from αKG while inactivating SDH and FH mutations generate high levels of succinate and fumarate, which are inhibitors of αKG-dependent dioxygenases including TET involved in demethylation of methylcytosine in DNA. Green arrows denote anaplerotic inputs into the Krebs cycle mediated by pyruvate carboxylase (PCB) () and glutaminase (GLS) reactions. { } encloses scrambled ¹³C labeling patterns of succinate, fumarate, malate, and Asp after one turn of the Krebs cycle. ●: ¹²C; OAA: oxaloacetate; HK: hexokinase; G6PDH: glucose-6-phosphate dehydrogenase; PDH: pyruvate dehydrogenase; IDH_m: isocitrate dehydrogenase mutant; PUR: purine synthesis; PYR: pyrimidine synthesis; PPP: pentose phosphate pathway; 1-C: one-carbon pathway; exo: exocyclic.

Inline graphic — The diagram depicts ¹³C tracing from ¹³C₆-glucose () or ¹³C/¹⁵N tracing from ¹³C₅,¹⁵N₂ glutamine () to the synthesis of nucleotides and effectors (dark red text) involved in epigenetic modifications, including αketoglutarate (αKG), 2-hydroxyglutarate (2HG), succinate, and fumarate. IDH1/2 mutants produce the histone demethylation inhibitor 2HG from αKG while inactivating SDH and FH mutations generate high levels of succinate and fumarate, which are inhibitors of αKG-dependent dioxygenases including TET involved in demethylation of methylcytosine in DNA. Green arrows denote anaplerotic inputs into the Krebs cycle mediated by pyruvate carboxylase (PCB) () and glutaminase (GLS) reactions. { } encloses scrambled ¹³C labeling patterns of succinate, fumarate, malate, and Asp after one turn of the Krebs cycle. ●: ¹²C; OAA: oxaloacetate; HK: hexokinase; G6PDH: glucose-6-phosphate dehydrogenase; PDH: pyruvate dehydrogenase; IDH_m: isocitrate dehydrogenase mutant; PUR: purine synthesis; PYR: pyrimidine synthesis; PPP: pentose phosphate pathway; 1-C: one-carbon pathway; exo: exocyclic.