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TOM SEYFRIED 2 | Cancer tumors need: glucose & glutamine for fuel or will die
presents episode 456 | Dr Thomas Seyfried
Dr Paul Mason podcast

Metabolism in normal cells: bulk of energy comes from…
-oxidative phosphorylation: 89% of energy produced
-very little energy comes
from glycolysis or from
the Krebs cycle
-which, in NORMAL
CELLS can work in the
presence or ABSENCE
of oxygen

Energy is key necessity for life…must know where it comes from
-in cancer cell, energy comes from totally DIFFERENT places
Cancer cell gets very
little energy from
oxidative phosphorylation
(cristae are abnormal)
Krebs cycle & glycolysis
generate 95% of energy
(non-oxidative processes)

Key shift: cancer cell is generating energy through…
different processes
How does this disturbed
energy metabolism
link to the hallmarks of

Focus on the origin of cancer:
damaged mitochondria; halting oxidative phosphorylation

Generates ROS (reactive oxygen species), which damage:
-nuclear genome lipids, proteins in the cell, causing mutations
-mutations are an EFFECT not a cause of cancer

Majority of cancer research has been focused on downstream
Real origin is related to functioning of mitochondria

Mitochondria send signal to nucleus:
“Incapable of sending enough energy to maintain cell life”
-genes then upregulate substrate-level phosphorylation

To run substrate-level phosphorylation, you need:
-fermentable fuels (glucose & glutamine)

-self-sufficiency in growth signals;
-insensitivity to anti-growth signals
-limitless replicative potential

proliferation was phenotype of all cells
on planet before oxygen
-leading to unbridled proliferation of cancer

leads to
-blood vessel development in cancer cells
-evasion of apoptosis (programmed death)

-mitochondria control apoptosis
(with damaged mitochondria, cell doesn’t die)

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