Figure 1.

Pyruvate and glutamate are 2 major metabolic hubs in GSCs. Tumor cells usually display a strong glycolytic metabolism. Glucose is uptaken by glucose transporter GLUT and then converted to pyruvate through several enzymes. All along this pathway, the glycolytic products are diverted from this main metabolic road to fuel other biosynthetic pathways such as the PPP as well as lipids and amino acids biosynthesis. PKM2 plays a key role in this dynamic process through conformational modulation. Glycolytic pyruvate will then either be converted to lactate or fuel mitochondrial OXPHOS and the TCA cycle. Another key metabolite that can fuel the TCA is glutamate once converted to αKG. Glutamate is produced either by GLS from glutamine or from glucose. Glutamate is involved in several biosynthetic pathways including amino acids and lipids biosynthesis as well as mitochondrial anaplerosis. Glutamate is also involved in glutathione synthesis, directly and indirectly by providing cysteine to the cells. α-KG, α-ketoglutarate; FAS, Fatty acid synthase; FBP1, Fructose-1,6 bisphosphatase 1; GCL, glutamate-cysteine ligase; GLS, Glutaminase; GS, Glutamine synthetase; GLUT, Glucose transporter 1; HK2, Hexokinase 2; IDH, Isocitrate dehydrogenase; LDHA, Lactate dehydrogenase A; MCT, Monocarboxylase transporter; MK, Mevalonate kinase; OAA, Oxaloacetate; PC, Pyruvate carboxylase; PDH, Pyruvate dehydrogenase; PDK, Pyruvate dehydrogenase Kinase; PKM2, Pyruvate kinase M2; PPP, Pentose phosphate pathway; TCA, Tricarboxylic acid cycle.