Regulation of Carbohydrates and Oxidative Stress Flashcards
How does adrenaline upregulate glycogen breakdown?
Adrenaline receptor stimulation > protein kinase cascade > activates glycogen phosphorylase
What is the physiological outcome of the effects of adrenaline on glucose metabolism?
Preparation for rigorous muscular activity > needs ATP
How does insulin upregulate glycogen synthesis in muscle?
Insulin receptor stimulation > protein kinase cascade > activates
- Glycogen synthase
- GLUT4 translocation to cell membrane
What is the physiological outcome of the effects of insulin on muscle?
Storage of glycogen
Why doesn’t insulin stimulate glycolysis in muscle?
Muscles aren’t doing anything > don’t need to it
How does insulin upregulate glycogen synthesis and glycolysis in the liver?
Insulin receptor stimulation > activates
- Glycogen synthase
- Key enzymes in glycolysis
What are the physiological outcomes of the effects of insulin on the liver?
Store glucose as glycogen
Generate acetyl-CoA for fatty acid synthesis
How does glucagon regulate glucose metabolism in the liver?
Glucagon receptor activation > inhibits - Glycogen synthase - All key enzymes in glycolysis Activates - Glycogen phosphorylase - Key enzymes in gluconeogenesis
What is the physiological outcome of the effects of glucagon on the liver?
Produce glucose > maintain blood glucose concentration
What molecules store reducing power within the cell?
NADH
FADH2
Where is most of the reducing power made within the cell?
Mitochondria
Can fatty acid degradation by beta-oxidation supply reducing power?
Yes
What is the role of NADH and FADH2 in oxidative phosphorylation?
Transfer of electrons from NADH and FADH2 across mitochondrial complexes > proton gradient across inner membrane
How are protons pumped into the intermembrane space in oxidative phosphorylation?
Energy from NADH > NAD
What is the proton gradient used for in oxidative phosphorylation?
Drive ATP synthesis by ATP synthase
Why must the steps in oxidative phosphorylation be smooth and have no delays?
Reactive oxygen species (ROS) made otherwise
What does hypoxia induce in the mitochondria in terms of oxidative phosphorylation?
Formation of superoxide at coenzyme Q (CoQ) step
How does hypoxia induce the formation of superoxide in oxidative phosphorylation?
Low oxygen level > transfer of electrons from CoQ to complex IV slows down
Electron at CoQ transferred to O2 to generate superoxide
Why does CoQ generate superoxide in hypoxia?
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
What are some of the effects of oxidative stress?
Acute DNA damage - mitochondrial and nuclear
Damaged DNA activates tumour suppressor p53
p53 induces
- Cell cycle arrest and repair
- Apoptosis
- Senescence
Why is mitochondrial DNA particularly susceptible to ROS damage?
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
