Flashcards in Fuel Metabolism and Cancer Deck (11):
What is the Warburg Effect
Most cancer cells cause increased glycolysis and lactate formation(instead of ATP) even when oxygen is present
Why is Warburg Effect favorable for cancer cells?
The primary cause of cancer is the replacement of the respiration of oxygen with fermentation of sugar. Instead of being oxidized, glucose is used to synthesize other compounds needed for rapidly proliferating cells.
What two compounds are taken up by cancer cells to form intermediates for synthesis of proteins. nucleic acids, and lipids? what does this do?
Glucose and glutamine
increase their biomass
What isozyme of pyruvate kinase is induced in cancer cells?
PKM2 which promotes oncogenic transformation and cell proliferation
What molecule inhibits PKM2? what happens to the pyrvuate
ROS-Mediated oxidation of certain cysteine residues
it reduced PEP->pyruvate and glucose enters pentose phosphate pathway where NADPH protects pyruvate from ROS
What happens to PFK-1 in cancer cells?
It is down-regulated by post-transitional modification (O-linked glycosylation) which put glucose into pentose phosphate pathway and ribose for nucleotides
What commonly happens to leukemia patients with isocitrate dehydrogenase?
mutation cause ability to form 2-hydroxyglutarate which activates glycolysis
What does glutamine do for cancer cells?
Only source of nitrogen for nucleotides and amino acids.
What transporter is responsible for glutamine uptake in cancer cells?
Na-dependent neutral amino acid transporter
What is the rationale of targeting metabolism for combinatorial strategy for cancer treatment?
high mutation rate genomic instability in cancer cells leads to increase rate of resistance to therapeutic agents.
Combinatorial strategies use more than one agent at a time and greatly reduce frequency of acquired resistance.