Tumour cell metabolism

Question 1

how do normal cells generate energy through glucose metabolism?

Answer 1

oxidative phosphorylation and glycolysis

Question 2

why is glycolysis energetically unfavourable

Answer 2

it takes a lot of energy to happen so you don’t get much energy out of it

Question 3

pro of glycolysis

Answer 3

allows instant ATP release, does not need O2

Question 4

where does glycolysis take place

Answer 4

cytosol

Question 5

products of glycolysis

Answer 5

2 pyruvate, 4 ATP and 4 NADH (remember 2 ATP used at start)

Question 6

what is the most of the energy generated from glycolysis used to drive

Answer 6

ADP+Pi

Question 7

is O2 used in glycolysis

Answer 7

no, but it is reduced so NADH can form

Question 8

what decarboxylates pyruvate and what is produced

Answer 8

pyruvate dehydrogenase complex, CO2 NADH and acetyl CoA

Question 9

what is generated from the krebs (TCA) cycle

Answer 9

3 NADH, 1FADH2, 1GTP (1 ATP)

Question 10

what is generated from the krebs cycle that is used for ANABOLIC pathways (5)

Answer 10

nucleotides, amino acids, glycolipids, glycoproteins, lipids/cholesterol

Question 11

where does the free oxygen used in TCA cycle come from

Answer 11

water

Question 12

what is the output of glycolysis per molecule of glucose

Answer 12

2 NADH and 4 ATP

Question 13

what is the output of pyruvate oxidation to acetyl CoA + Krebs per molecule of glucose

Answer 13

8 NADH, 2 FADH2, 2GTP, 36ATP

Question 14

overall amount of ATP gained

Answer 14

38

Question 15

what transporter aids the movement of glucose into cells

Answer 15

GLUT1

Question 16

why don’t tumour cells have a normal metabolism?

Answer 16

they are proliferating so have different environments, abnormal blood supply, different genome (oncogenes)

Question 17

how is metabolism reprogrammed in tumour cells

Answer 17

oncogenic activation, mutation in cMYC and ras have effects on metabolic genes

Question 18

how can p53 aid metabolic reprogramming

Answer 18

it directly regulates activity/expression of key pathways involved in metabolism

Question 19

what can oncogenesis do to HIF

Answer 19

stabilise it

Question 20

what happens if GLUT1 becomes hyperactive

Answer 20

massive increase in metabolism

Question 21

how does GLUT1 become upregulated

Answer 21

mutation in MAP kinase signalling pathway

Question 22

what happens if you start increasing the glycolysis pathways

Answer 22

there is a shift in the cells metabolic status

Question 23

what happens when the metabolic status is shifted

Answer 23

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)

Question 24

what happens when there is more glycolysis in terms of enzymes

Answer 24

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

Question 25

what happens to lactate in aerobic conditions

Answer 25

it is converted back to pyruvate

Question 26

what happens to lactate in hypoxic conditions

Answer 26

it is excreted from cells

Question 27

what enzyme has increased activity in tumour cells which leads to an increase in lactate secretion

Answer 27

lactate dehydrogenase, it causes an increase in pyruvate kinase M2 and promotes lactate pathway

Question 28

what does an increase in lactate dehydrogenase for tumour cells in terms of glycolysis

Answer 28

they can maintain glycolysis for much longer, no accumulation of lactate, more acidification of the matrix which can lead to enzyme inhibition

Question 28

what happens when you target tumour cell metabolism

Answer 28

you can slow tumour growth

Question 29

how do tumours avoid radiotherapy?

Answer 29

radiotherapy needs oxygen to work but tumours can survive more hypoxic environments

Question 30

what did Otto Warburg notice

Answer 30

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

Question 31

What is The Warburg effect

Answer 31

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