L4 : Mechanisms of Redox Regulation

Question 1

What are redox reactions?

Answer 1

Reduction oxidative reactions mediated by transfer of electrons
Cellular respiration = oxidation of glucose to CO2 and reduction of O2 to water

Question 2

What are free radicals?

Answer 2

Highly reactive and unstable
Can become harmful if not reattached to redox molecule or antioxidant
Can damage DNA and cause mutations, leading to oncogenic transformation

Question 3

How are free radicals generated?

Answer 3

Produced as byproduct of metabolism, detoxification pathways etc.
Generation involved in mechanism of immune cells to kill bacteria

Question 4

Examples of common free radicals in cells?

Answer 4

Superoxide anion (O2)
Hydroxyl radical (OH)
Peroxyl radical (ROO)
Hypochlorous acid (HOCl)
Peroxynitrite anion (ONOO-)
Nitrogen monoxide (NO*)

Question 5

How is redox homeostasis regulated?

Answer 5

Control of redox reactive species production and removal is essential to redox homeostasis

Question 6

What are the 3 major families of redox reactive species?

Answer 6

All are cellular metabolites
Reactive oxygen (ROS)
eg. O2-, H2O2, *OH, HOCl, ONOO-
Reactive nitrogen (RNS)
Reactive sulphur (RSS)

Question 7

What are the main sources of ROS production in mammalian cells?

Answer 7

• Mitochondria (ETC)
• Plasma membrane GFR signalling (NADPH oxidase)
• Endoplasmic reitculum (misfolded proteins)
• Extracellular stresses (radiation, xenobiotics, mcirobes)
• Detoxificatin pathways (metabolising enzymes

Question 8

What are examples of diseases caused by oxidative stress?

Answer 8

• Cancer
• Neurodegeneration
• Diabetes
• Myocardial infarction
• Chronic inflammation
• Atherosclerosis

Pathogenesis of these pathologies is associated with ROS-induced damage to proteins, lipids, DNA

Question 9

How can redox communication occur in cells?

Answer 9

1. Through reversible and irreversible modifications of protein sulfhydryl groups (-SH, mainly on Cys and Met residues)
2. Changes occur in response to oxidative or metabolic stress
   - Type of modification depends on source and intensity of stress
3. Low molecular weight thiols function as major antioxidants to help regulate redox signalling

Question 10

What are the cellular targets of oxidative damage?

Answer 10

DNA
Lipids
Proteins

Question 11

What are the main antioxidant defence enzymes in mammalian cells?

Answer 11

1. Superoxide dismutase (SOD)
   - Superoxide -> H2O2
2. Catalase (CAT)
   - H202 -> H2O + O2
3. Glutathione peroxidase (GPx)
   - H202 + GSH -> H2O +GSSG
   - (Glutathione -> Glutathione disulfide)
4. Glutathione reductase (GR)
   - Reduces glutathione disulfide into glutathione

Note: H2O2 can be reduced into OH* in presence of iron (fenton reaction)

Question 12

What is the role of GSH in redox regulatio and cellular functions?

Answer 12

Protein folding
Proliferation and apoptosis
DNA repair
Energy production
Antioxidant defense
Transcription
Signalling
Differentiation

Question 13

Redox regulation and oxidative stress

Answer 13

EXPAND