Figure 2

Simplified schema of major metabolic fluxes in (a) aerobic non-malignant cells and (b) hypoxic tumor cells of breast carcinoma. Thickness of arrows and bold text indicate relative intensity of fluxes. CL, citrate lyase; CS, citrate synthase; IDH1, isocitrate dehydrogenase 1; PDH, pyruvate dehydrogenase. According to Metallo et al. [21], the increased flux from glutamine into the Krebs cycle by mutation of IDH1 provides the acetyl-CoA for lipid biosynthesis under hypoxic conditions, because most pyruvate in cancer cells is converted to lactate. Increase in flux through the pentose phosphate pathway delivers ribose-5-phosphate needed for DNA synthesis and NADPH required for lipid biosynthesis. Conversely, less NADH is produced through pyruvate dehydrogenase or the Krebs cycle, as mitochondrial respiration for ATP production is less favored.