What distinguishes tumor metabolism from that of a normal cell?
By what standard of scientific evidence can we understand the key differences between the energy production capabilities of a tumor cell, in comparison to that of a normal cell.
Crucially, one can observe that in normally respiring cell, mitochondrial ATP is mostly produced from oxidative phosphorylation, where approximately 89% of total cellular energy is produced, at about 32 to 36 total ATP molecules during the complete oxidation of glucose, depending on the cell type.
However, tumor cells generate ATP via pathways that do not rely on oxidative phosphorylation, given that the number, structure and function of mitochondria in tumor cells are damaged, as evidenced by alterations in mitochondrial lipids and enzymes of the electron transport chain, and abnormalities in mitochondrial-associated membranes, a downregulation in cardiolipin, along with partial or total cristolysis predominate in malignant tumors.
Hence, a shift from energy production through oxidative phosphorylation to energy production via substrate level phosphorylation in the glycolysis and glutaminolysis pathways, represent the common phenotype of all cancers.
Therefore, diminished cellular oxidative phosphorylation, coupled with increased substrate level phosphorylation activities, can maintain adequate hydrolysis for cell viability during a gradual transition from a well differentiated oxidative phosphorylation-dependent state, to a fully malignant substrate level phosphorylation-dependent state.
Decidedly, the path to cellular carcinogenesis will occur only in those cells capable of enhancing energy production through substrate level phosphorylation of glucose and glutamine. Cells that cannot transition from oxidative phosphorylation to substrate level fermentation will die, and thus cannot become tumorigenic.