L14: Energy Metabolism Flashcards
Why is it important to consider tumour metabolism?
Different cancers have different metabolic requirements & environments hence impacts treatment e.g. if T cells enter unknown environment, it won’t function properly
Relating energy metabolism to hallmarks of cancer
For each hallmark to occur, there must be a metabolic chang e.g. for self sufficiency in growth signals, new protein, RNA 7 DNA must be made
Importance of mitochondria in apoptosis?
Increased mitochondrial membrane potentioal –> evasion of apoptosis
Increased proliferation –> increased TCA cycle activity –> increased proton pumping –> evasion of apoptosis
What is the Warburg effect?
Increased lactate production by cells in AEROBIC conditions, shown by cancer & other cells e.g. brain
Mostly from glycolysis
What is FDG PET scanning?
2-FDG (radioactively labelled glucose) taken up by cancer cells & shows up in PET scanning
Useful for diagnosing metastasis
Why do cancer cells require TCA cycle & oxidative phosphorylation?
GLycolysis doesn’t generate enough energy per glucose despite fast rate
TCA & OP can be used w many diff substrates e.g. AA, fatty acids, ketone bodies - useful in glucose deprivation
Why may microbiota be key to cancer metabolism?
Source of essential AA used by cancer cells
Converts fructose –> glucose in gut
Where is ATP made within cancer cells?
Glycolytic enzymes attached to cytoskelton e.g. actin so glycolysis occurs in cell motility areas - allows migration + metastasis as energy can be generated quickly
TCA & OP in mitochondria found around nucleus - lots of ATP can be made for nucleoside production
What can cause Warburg effect in cancer cells?
Mutations in oncogene/TSG –> increased proliferation e.g. PTEN, p53, K-Ras, C-Myc
Why is p53 needed for metabolism? Why can p53 mutation cause Warburg effect?
Synthesis & activation of components needed for OP e.g. SCO2
Translation of glucose transporters
Reprogrammes glycolysis to increase ability to use glucose
w/o p53, OP can’t be increased hence cells rely on glycolysis in aerobic condition –> WARBURG EFFECT!
What is SCO2?
Required to make aspect of respiratory chain e.g. COX II–> production og cytochrome-c oxidase complex
why can glycolysis still occur if there’s p53 mutation?
p53 retains ability to upregulate enzymes invovled in glucose uptake, ATP generation via glycolysis + TCA, DNA + RNA synthesis, detoxification in oxidative stress
BUT can’t synthesis SCO2
Which is better no p53 or mutated p53 for cancer cells?
mutated p53 gives survival advanatge:
- better at dealing oxidative stress
- increased glycolytic activity hence outcompetes other cells in O2 deprivation
- can hence proliferate quicker, lots of DNA + RNA made
How does c-Myc mutation affect metabolism?
Drives glucose & glutamine uptake - glucose used in glycolysis –> warburg effect.
Glutamine used in TCA –> evasion of apoptosis
Increased ribosomal mass via protein synthesis
Where is K-Ras mutation found
Pancreatic cancer
