64 - Mitochondrial Energy Pathways

Question 1

Reducing powers generated by oxidative phosphorylation

Answer 1

NADH and FADH2

Question 2

Where are NADH and FADH2 oxidised in ATP generation?

Answer 2

Electron transport chain

Question 3

Role of pentose phosphate pathway

Answer 3

Generation of NADPH for reductive biosynthesis of reduced glutathione and reductive biosynthesis of proteins and nucleic acids.

Question 4

Oxidation in organic chemistry
1
2

Answer 4

Decreases electron density on carbon by:

1. Forming one of these: C-O, C-S; C-N; and C-X (X: F, Cl, Br or I), or
2. Breaking this: C-H; C-C

Question 5

Broad principle of generation of reducing agents with ATP generation pathways

Answer 5

Dehydrogenation (oxidation) leads to H+ joining with NAD- or FADH- to form NADH or FADH2.

This can happen in TCA cycle, fatty acid oxidation

Question 6

Role of complexes I to IV in electron transport chain

Answer 6

Generate a protein gradient across the inner membrane of mitochondria, to be pushed through ATP synthase to generate ATP.

Question 7

What donate H+ to complexes I to IV for oxidative phosphorylation?

Answer 7

NADH (complexes I to IV) and FADH2 (complexes II to IV)

Question 8

Role of flavin mononucleotide (FMN) and ubiquinone

Answer 8

Electron conveyors that are readily oxidised and reduced.

Move electrons in oxidative phosphorylation

Question 9

Coenzyme Q role

Answer 9

Accept electrons from electron transport chain, which are used to generate water.

Question 10

Effect of coenzyme Q buildup

Answer 10

If the process of CoQ accepting e- is slowed down too much, you can get a buildup of CoQ, which reduces O2 to superoxide

Question 11

What catalyses glutathione synthesis?

Answer 11

Glutathione reductase

Question 12

Main pathway in NADPH generation in the cytosol

Answer 12

Pentose phosphate pathway

Question 13

Role of glutathione

Answer 13

Can rescue oxidised proteins

Question 14

Oxidative stress role in cancer cell apoptosis
1
2
3

Answer 14

• Oxidative damage to DNA
• Activation of tumour suppressor p53 in nucleus
• Expression of proteins inducing cell cycle arrest and cell death

Question 15

Warburg effect

Answer 15

Most cancer cells generate ATO through glycolysis, even with normal O2 levels.
Most cancer cells therefore convert glucose to lactate and do not metabolise it in TCA cycle and oxidative phosphorylation.

Question 16

Why do cancer cells often generate a very acidic environment?

Answer 16

Warburg effect

Question 17

Under normal conditions, what happens to lactate generated by glycolysis?

Answer 17

Lactate secreted from cells, goes to liver, used as a substrate for gluconeogenesis

Question 18

GLUT activity in cancer cells

Answer 18

GLUT1 overactivity

Question 19

How can cancers be imaged?

Answer 19

Give 2-deoxy 2(18F)fluoro-D-glucose to patient, which accumulates in cancer cells (because of overactive GLUT1 receptors)
Using a PET scan to image this.

Question 20

More common H+ carrier in mitochondria

Answer 20

NADH is higher concentration in mitochondria, lower in cytosol.
NADPH is the opposite.

Question 21

Stages of pentose phosphate pathway at which NADPH is generated.

Answer 21

Two stages:
One for forming NADPH to form glutathione.
One for forming NADPH for generation of fatty acids, sterols, etc (reductive biosynthesis)

Question 22

Effect of Warburg effect and hypoxia-induced metabolic adaptation in cancer cells

Answer 22

Scavenge ROS, which prevents DNA damage in nucleus and mitochondria, which prevents activation of p53.

Question 23

Adaptations of tumour cells to tumour microenvironment (hypoxia, low pH, autophagy)
1
2
3

Answer 23

ATP, NADPH generation (glycolysis and pentose phosphate pathway)

Precursors for synthesis of DNA, protein

Glutathione synthesis to reduce ROS

Question 24

Molecule that starts pentose phosphate pathway

Answer 24

Glucose-6-phosphate

Question 25

Rationale behind Warburg effect

Answer 25

Warburg effect represents a type of metabolic adaptation of cancer cells to avoid cell senescence and promote cell growth and proliferation