Fig. 4

Glucose and lipid metabolism in cancer cells under hypoxic conditions. Glucose is taken up by cancer cells via GLUT1 and glycolysed to pyruvate via PKM, PGK1 and PGAM1. Hypoxic cancer cells promote pyruvate glycolysis to lactate by upregulating LDHA, LDHC and LDH-5, and the lactate produced is excreted outside the cell via MCT1/4. In addition, HIF-1α inactivates PDH by activating PDK1, which in turn fails to convert pyruvate to acetyl-CoA, preventing the entry of pyruvate into the TCA cycle. Cytoplasmic citrate is catalyzed by ALCY to acetyl-CoA, and acetyl-CoA catalyzed by ACC to malonyl-CoA. Acetyl-CoA and malonyl-CoA are catalyzed to FA via FASN upregulated by SREBP-1. SCD1 upregulated by SREBP-1 catalyzes the formation of MUFA from saturated FA. PHD3 loss reduces ACC2 hydroxylation and promotes FAO to provide energy. α-KG as a product of glutamine is reduced and carboxylated to isocitrate by IDH, and then oxidation to citrate. PLD hydrolyzes PC to produce PA. PLA2 catalyzes the hydrolysis of GPL to produce Lyso-PL