Lecture 16 - Metabolism in Development & Cancer Flashcards
What do ligands bind to? Does this happen on the inter or extracellular side?
Receptor on extracellular side of the membrane
Which hormone/growth factor stimulates glycolysis, FA oxidation etc.
Insulin
The availability of oxygen determines the fate of glycolysis in the cells (either pyruvate or lactate). Do cancer cells have this same dependence on oxygen availability?
No - not driven by oxygen availability
When ATP requirements are low, oxygen availability is/is not rate limiting?
When ATP requirements are high, oxygen availability is/is not rate limiting?
Low = no High = rate limiting potentially
What are 3 changes in cellular metabolism during tumorigenesis?
- Substrate uptake
- Altered intracellular partitioning
- Influencing the tumour metabolic microenvironment
How does the “Warburg effect” affect lactate & glucose concentrations in cells with sufficient oxygen but have tumours (cancer)?
Glucose = the rate of glucose release is v high compared to normal cells Lactate = major increase in lactate production even though sufficient oxygen is available (in normal cells it is low because enough oxygen means it doesnt have to be converted to lactate)
Does increased lactate production result in a microenvironment that is more acidic or basic?
Acidic - pH drops to ~ 6.7
MICROENVIRONMENT ACIDIFICATION
Summary of the Warburg Effect
The WE is about glucose uptake & lactate production. The flow on effect is microenvironment acidification
Comparison of centre to regional parts of tumour cells.
Page 26 of slides.
All cholesterol (which makes steroids) is built from
Acetyl-CoA
What are the 4 key similarities between METABOLISM in EMBRYOS & TUMOUR CELLS?
- Increased glucose uptake, independent of O2 (almost Warburg like)
- Increased biomass
- Increased glutamine utilisation
- Expression of PKM2 and increased at the blastocyst stage (not PKM1)
