Figure 9.

Comparison of metabolic profile changes associated with A) deuterium depletion or B) Glivec in leukemia and Metformin (MET) in Mia-PaCa cells. In normal cells natural deuterium depletion occurs via mitochondria-dependent NAD(P)H production, a process compromised in all cancer cells. Glivec restores and Metformin improves mitochondrial fatty acid substrate oxidation with TCA cycle turnover and increase fumarate hydratase, hence low deuterium-containing metabolic water recycling for NAD(P)H-driven reductive macromolecule synthesis of the normal mammalian cell. Glivec and Metformin treatment also strongly inhibit the oxidative deuterium loading arm of the pentose cycle from free water (panel B). Deuterium depletion in free (drinking) water and the serum of pancreatic cancer patients mimic restored mitochondrial deuterium depletion for reductive synthesis via limiting deuterium load through oncogenic NAD(P)D production in the oxidative arm of the pentose cycle (panel A), regardless of compromised mitochondrial activity thus “tricking” tumor cells.