Diabetes and Its Link with Cancer: Providing the Fuel and Spark to Launch an Aggressive Growth Regime

Figure 2

Glycolysis and glutaminolysis are two of the most important pathways for cancer cells. Increased glucose uptake, together with reduced glycolytic flux, accumulates glycolytic intermediates for synthesis of biomolecules such as nucleotides, amino acids, and lipids. Similarly, glutamine uptake is also increased. Glutamine is converted to glutamate by mitochondrial glutaminase. Glutamate is then converted to α-ketoglutarate which can be oxidised in the TCA cycle to generate ATP or reductively carboxylated to citrate. Citrate is exported to the cytoplasm where it is converted to acetyl-Co-A or oxaloacetate, which are used for synthesis of fatty acids or amino acids, respectively. Metabolic changes in cancer cells are driven by changes in the regulation of critical enzymes. Examples of these enzymes are shown in bold. Regulation of metabolic pathways by oncogenes (Myc and K-Ras) and tumour suppressor genes (p53) is also shown. Glycolysis is shown in red. Glutaminolysis is shown in orange. Biosynthetic pathways are shown in green. Other pathways are shown in grey.