L14: Energy Metabolism Flashcards Preview

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Flashcards in L14: Energy Metabolism Deck (19):

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


How does K-ras mutation affect metabolism?

- drives uptake of external proteins (micropinocytosis)
- degraded to AA + used to generate new proteins for ATP, DNA, RNA
- Hence diff source of nutrients (apart from glucose + glutamine)
Can also engulf collagen matrix around it, utilise breakdown products of other dying cells --> survival advantage
Also increases glycolysis via AKT activation


Why is pancreatic cancer highly aggressive?

Both p53 and K-ras mutation present, can survive <0.1% O2


What are some familal syndromes involving metabolic change?

- inheritence of mutates succinate dehydrogenase --> pheochromocytoma + paraganglioma
- mutation of fumarate hydratase --> leiomyoma (fibroids) + renal cell carcinoma


What does mutation in succinate dehydrogenase + fumarate hydratase cause

Causes increase in succinate + fumarate preventing TCA cycle function, this stabilises HIF despite normoxia
--> pseudohypoxia - HIF increases expression of glycolytic enzymes --> glycolytic switch + Warburg effect