A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

Figure 1

Metabolic flux in the pentose phosphate pathway (PPP) after oxidative stress and/or GAPDH inhibition in cells (adapted according to Kuehne et al. [31]). The metabolic rerouting in oxidative and nonoxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance. Acute activation of oxidative PPP is considered a first-line response to oxidative stress in cells. Oxidants induce rerouting of glucose flux into oxidative PPP within seconds. Initial rerouting is independent of GADPH inhibition. Multiple cycling of carbon compounds in the oxidative PPP potentially amplifies NADPH production. The metabolic PPP activation might be involved in resistance against ROS, particularly in cancer cells. Gray arrow indicates that in cancer cells this step is not reversible due to the loss of fructose-1,6-bisphosphate activity. The black blunt end indicates the inhibition of GAPDH. G6DH: glucose-6-phosphate dehydrogenase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; PPP: pentose phosphate pathway; ROS: reactive oxygen species.