Cancer Etiology: A Metabolic Disease Originating from Life’s Major Evolutionary Transition?

Figure 1

O₂ and NAD+ as limiting factors in driving oxidative phosphorylation. The figure presents a hypothesis that in situations with limited availability of NAD+, the cells will activate the program which switches off Krebs cycle and electron transport chain (process consumes 6 NAD+) and favors glycolysis (process consumes 2 NAD+) in order to obtain energy, preserve NAD+, and avoid cell death through reduced ATP production and activation of apoptosis. Abbreviations: PARP: poly(adenosine diphosphate [ADP] ribose) polymerases; CD38: NAD+ glycohydrolases; sirtuins: NAD-dependent histone deacetylase (“HDAC”) enzymes.