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BMS379 - Cancer Biology > L9 - Reprorgamming Metabolism > Flashcards

L9 - Reprorgamming Metabolism Flashcards

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1
Q

Two ways ATP is generated

A

Glycolysis and aerobic respiration (TCA)

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2
Q

Net yield from glycolysis

A

2 ATP

2 NADH

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3
Q

Net yeild from krebs cycle

A

2 ATP

Then 6NADH generates 34 ATP

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4
Q

What can be said RE the efficiency of cancer cells metabolism

A

Low efficiency

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5
Q

What metabolism do cancer cells use - whiy is this unsual

What is this known as

A

Glycolysis - they use this even in the presence of oxygen

This is the WARBURG EFFECT

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6
Q

Upregulation of _____ helps the cancer cell to deal with

A

GLUT1

Lack of ATP

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7
Q

Role of GLUT-1

A

Glucose in

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8
Q

How can we see this upregulation of GLUT1 (two wasy)

A

Immunohistochemsitry

Histochemical in-situ hybridisation
Radio-RNA - massive upregulation

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9
Q

GLUT1 upregualtion can be used as a

A

Diagnostic marker

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10
Q

How can GLUT1 upregulation be used as a diagnostic marker

A

Use radio-F and then PET scan

Glucose will accumulate in cells where this upregulation has happened - marks turmours

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11
Q

What is the role of high glucose flux in cancer cell

A

To fascilitate the higher levels of ATP production anaerobically

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12
Q

Describe what is seen when performing metabolic studies of thymocytes which have been isolated by density gradient centrifugation

A

Addition of glucose - reduces O2 consumption - CRAB TREE EFFECT - suggests things slighlty different in proliferating cells

Huge increases in lactate

See most ATP comes from glycolysis

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13
Q

When cells are proliferating the main way of producing ATP is through

A

High flux glycolysis

This is where the same ammount of ATP is generated - just from more glucose since the process is so inefficient

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14
Q

What can explain metabolic repurpossing

A

Oncogenes and loss of tumour supressor genes

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15
Q

What signalling promotes metabolic transformation

A

PI3K and Akt

This is through multiple signalling pathways

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16
Q

What multiple pathways can lead to metabolic repurpossing

A

Increase expression of nutrient transporters enabling increased uptake
Akt dependent stimulation of hexokinase and phosphfructokinase - drives glycolysis
Enhanced transcription involved in glycolysis and lipogenesis
Enhanced translation through mTOR pathway

17
Q

What is pyruvate used for

A

Many processes such a lipid synthesis

18
Q

What is myc

What is it required for

A

Early serum response transcription

Required for proliferation

19
Q

Describe the structure of Myc

A

Alpha helix with a leucine zipper

20
Q

What does myc dimerise with

A

MAX

21
Q

Describe what happens in ordinary circumstances

A

Myc present in limited amounts (unlike MAX)
Levels increase in presence of serum
Promotes proliferative genes

Explains its protooncogenic status

22
Q

Myc mutated in how many tumours

A

30%

23
Q

Myc upregulates ….

By ….

A

Glycolytic enzyme transcription by binding to an upstream consensus sequence

24
Q

How was it shown Myc binds to a sensensus sequence - upregulating proliferative genes

A

Using a chromatin IP workflow
Cross DNA-protein using cross linking agents
Sheer DNA strands by sonication
Add AB to immunoprecipitate with DNA - wash to reverse linkage
Can isolate DNA
PCR to amplify
Identification of the gene

25
Q

What is the chromatin IP workflow a useful model for

A

Burkitts lymphoma

26
Q

What genes coprecipate with Myc antibodies

A

Enolase
Hexokinase
Lactate dehydrogenase

27
Q

Myc is

A

Strongly growth promoting

28
Q

HIF is

A

Strongly growth inhibiting

29
Q

Describe the P493-6 cell model of Burkitts lymphoma

A

Tetracycline represses Myc expression

Kim et al. introdcued oxygen insensitive HIF1 to avoid complications with feedback

30
Q

HIF1 promotes

A

Myc-induced tumourigenesis

THIS IS THROUGH PROMOTING EXPRESSIONS OF
Hexokinase 2 and pyruvate dehydrogenase 1

31
Q

Describe what is seen in tumours with HIF1 as well

A

Volume of tumours with HIF1 are even bigger

32
Q

What is the effect of the expression of hexokinase and lactatate dehydrogenase

A

Encourages glycolysis whilst simulatenaeously shutting down oxidative phosphorylation

BMS379 - Cancer Biology (11 decks)

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