Tumour cell metabolism Flashcards
how do normal cells generate energy through glucose metabolism?
oxidative phosphorylation and glycolysis
why is glycolysis energetically unfavourable
it takes a lot of energy to happen so you don’t get much energy out of it
pro of glycolysis
allows instant ATP release, does not need O2
where does glycolysis take place
cytosol
products of glycolysis
2 pyruvate, 4 ATP and 4 NADH (remember 2 ATP used at start)
what is the most of the energy generated from glycolysis used to drive
ADP+Pi
is O2 used in glycolysis
no, but it is reduced so NADH can form
what decarboxylates pyruvate and what is produced
pyruvate dehydrogenase complex, CO2 NADH and acetyl CoA
what is generated from the krebs (TCA) cycle
3 NADH, 1FADH2, 1GTP (1 ATP)
what is generated from the krebs cycle that is used for ANABOLIC pathways (5)
nucleotides, amino acids, glycolipids, glycoproteins, lipids/cholesterol
where does the free oxygen used in TCA cycle come from
water
what is the output of glycolysis per molecule of glucose
2 NADH and 4 ATP
what is the output of pyruvate oxidation to acetyl CoA + Krebs per molecule of glucose
8 NADH, 2 FADH2, 2GTP, 36ATP
overall amount of ATP gained
38
what transporter aids the movement of glucose into cells
GLUT1
why don’t tumour cells have a normal metabolism?
they are proliferating so have different environments, abnormal blood supply, different genome (oncogenes)
how is metabolism reprogrammed in tumour cells
oncogenic activation, mutation in cMYC and ras have effects on metabolic genes
how can p53 aid metabolic reprogramming
it directly regulates activity/expression of key pathways involved in metabolism
what can oncogenesis do to HIF
stabilise it
what happens if GLUT1 becomes hyperactive
massive increase in metabolism
how does GLUT1 become upregulated
mutation in MAP kinase signalling pathway
what happens if you start increasing the glycolysis pathways
there is a shift in the cells metabolic status
what happens when the metabolic status is shifted
more lactate is produced, the cellular environment is more acidic and that changes how proton pumps work. oxidative phosphorylation pathways are less dominant in the cells (they still happen a bit though)
what happens when there is more glycolysis in terms of enzymes
enzymes are produced which inhibit the further downstream pathways, therefore there is a shutting off of some of the enzyme activity which is needed for oxidative phos
what happens to lactate in aerobic conditions
it is converted back to pyruvate
what happens to lactate in hypoxic conditions
it is excreted from cells
what enzyme has increased activity in tumour cells which leads to an increase in lactate secretion
lactate dehydrogenase, it causes an increase in pyruvate kinase M2 and promotes lactate pathway
what does an increase in lactate dehydrogenase for tumour cells in terms of glycolysis
they can maintain glycolysis for much longer, no accumulation of lactate, more acidification of the matrix which can lead to enzyme inhibition
what happens when you target tumour cell metabolism
you can slow tumour growth
how do tumours avoid radiotherapy?
radiotherapy needs oxygen to work but tumours can survive more hypoxic environments
what did Otto Warburg notice
some cell types increased lactate production in response to low O2, he found tumour cells do this all the time even with loads of O2. He showed there was a disconnect between O2 consumption and respiration - not same input and output as in normal cell type
What is The Warburg effect
Aerobic glycolysis, cancer cells are marked out by this. 80% of ATP is from glycolysis in a tumour cell, not because Oxi phos is turned off but because there is an increase in glycolysis
