FIGURE 4.

Schematic representation of some involved pathways in C8- and C10-treated cells, on the basis of Metabolic Pathway analysis. In the mitochondrial matrix, glutamine can be converted, through glutaminase (GLS) activity, in glutamate and then in α-ketoglutarate (glutamine and glutamate metabolism). In cancer cells, α-ketoglutarate can converge toward citrate that, after conversion in acetyl-CoA in the cytosol, represents the primer for lipid synthesis. α-Ketoglutarate can also generate citrate through the oxidative metabolism in the citric acid cycle, forming succinate, fumarate, malate, oxaloacetate, and citrate. Mitochondrial acetyl-CoA can derive also from fatty acids β-oxidation or glycolytic pyruvate through the activity of pyruvate dehydrogenase complex (PDH). When in the mitochondrial matrix acetyl-CoA exceeds OAA amounts, acetyl-CoA can be used for ketone body production (ketone body metabolism). However, cancer cells can also produce a high level of lactate from glycolytic pyruvate, also in the presence of functioning mitochondria (Warburg effect).