Regulation of Carbohydrates and Oxidative Stress

Question 1

How does adrenaline upregulate glycogen breakdown?

Answer 1

Adrenaline receptor stimulation > protein kinase cascade > activates glycogen phosphorylase

Question 2

What is the physiological outcome of the effects of adrenaline on glucose metabolism?

Answer 2

Preparation for rigorous muscular activity > needs ATP

Question 3

How does insulin upregulate glycogen synthesis in muscle?

Answer 3

Insulin receptor stimulation > protein kinase cascade > activates

• Glycogen synthase
• GLUT4 translocation to cell membrane

Question 4

What is the physiological outcome of the effects of insulin on muscle?

Answer 4

Storage of glycogen

Question 5

Why doesn’t insulin stimulate glycolysis in muscle?

Answer 5

Muscles aren’t doing anything > don’t need to it

Question 6

How does insulin upregulate glycogen synthesis and glycolysis in the liver?

Answer 6

Insulin receptor stimulation > activates

• Glycogen synthase
• Key enzymes in glycolysis

Question 7

What are the physiological outcomes of the effects of insulin on the liver?

Answer 7

Store glucose as glycogen

Generate acetyl-CoA for fatty acid synthesis

Question 8

How does glucagon regulate glucose metabolism in the liver?

Answer 8

Glucagon receptor activation > inhibits
- Glycogen synthase
- All key enzymes in glycolysis
Activates
- Glycogen phosphorylase
- Key enzymes in gluconeogenesis

Question 9

What is the physiological outcome of the effects of glucagon on the liver?

Answer 9

Produce glucose > maintain blood glucose concentration

Question 10

What molecules store reducing power within the cell?

Answer 10

NADH

FADH2

Question 11

Where is most of the reducing power made within the cell?

Answer 11

Mitochondria

Question 12

Can fatty acid degradation by beta-oxidation supply reducing power?

Answer 12

Yes

Question 13

What is the role of NADH and FADH2 in oxidative phosphorylation?

Answer 13

Transfer of electrons from NADH and FADH2 across mitochondrial complexes > proton gradient across inner membrane

Question 14

How are protons pumped into the intermembrane space in oxidative phosphorylation?

Answer 14

Energy from NADH > NAD

Question 15

What is the proton gradient used for in oxidative phosphorylation?

Answer 15

Drive ATP synthesis by ATP synthase

Question 16

Why must the steps in oxidative phosphorylation be smooth and have no delays?

Answer 16

Reactive oxygen species (ROS) made otherwise

Question 17

What does hypoxia induce in the mitochondria in terms of oxidative phosphorylation?

Answer 17

Formation of superoxide at coenzyme Q (CoQ) step

Question 18

How does hypoxia induce the formation of superoxide in oxidative phosphorylation?

Answer 18

Low oxygen level > transfer of electrons from CoQ to complex IV slows down
Electron at CoQ transferred to O2 to generate superoxide

Question 19

Why does CoQ generate superoxide in hypoxia?

Answer 19

Oxidised CoQ reduced in 2 steps
1) Accept 1st electron to form unstable partially reduced CoQ intermediate
2) Intermediate needs to quickly accept another electron to form fully reduced CoQ
Insufficient oxygen slows down 2nd step
3) Unpaired electron transferred to O2 to generate superoxide

Question 20

What are some of the effects of oxidative stress?

Answer 20

Acute DNA damage - mitochondrial and nuclear
Damaged DNA activates tumour suppressor p53
p53 induces
- Cell cycle arrest and repair
- Apoptosis
- Senescence

Question 21

Why is mitochondrial DNA particularly susceptible to ROS damage?

Answer 21

Lack of histones > no protection
DNA repair mechanisms poorly developed
DNA damage causes defective/no expression of proteins for assembly of new oxidative phosphorylation complexes > generate more ROS