Figure 2

Concept map of the cancer metabolic rewiring. Large glycolytic flux and complex I dysfunction are required to sustain glutamine reductive carboxylation. Yellow arrows identify glycolysis. Blue arrows identify glutamine metabolism, green arrows identify pentose phosphate pathway (PPP), bright Lilac identifies serine/glycine/one-carbon-folate-metabolism, and red arrows identify an NAD(P)H electron transfer flux (ETF). NAD(P)H ETF originates from serine diversion pathway, sustains lipid synthesis, ROS quenching by GSH and reductive steps of non-essential amino-acid (NEAA) synthesis. Abbreviations: 1,3BPGA, bisphosphoglycerate; 3PGA, 3phosphoglycerate; 6PGL, 6-phosphogluconolactone; AcCoA, acetyl-CoA; ACL, ATP citrate lyase; Akg, α-ketoglutarate; Ala, alanine; Arg, arginine; Asn, asparagine; Asp, aspartate; CH⁺-Thf, 5-methylenetetrahydrofolate; CH₂-Thf, 5,10-methylenetetrahydrofolate; Cit, citrate; Cys, cysteine; F1,6BP, fructose 1,6 biphosphate; FFA, fatty acids; G6P, glucose 6-phosphate; GA3P, glyceraldehyde 3-phosphate; Glc, glucose; Gln, glutamine; Glu, glutamate; Gly, glycine; GOT, glutamic-oxaloacetic transaminase; GSH, glutathione reduced; GSSG, glutathione oxidized; Lac, lactate; LDHA, lactate dehydrogenase; MDH 1, malate dehydrogenase; ME, malic enzyme; MTHFD1 and 2, methylenetetrahydrofolate dehydrogenase (NADP⁺ dependent); NEAA, non-essential amino acids; Oaa, oxalacetate; PPP, pentose phosphate pathway; P-Pyr, 3-phosphohydroxypyruvate; Pyr, pyruvate; R5P, ribose 5-phosphate; ROS, reactive species oxygen; Ser, serine; SHMT1 and 2, serine hydroxymethyltransferase