Antioxidants & Generation of Reactive Oxygen Species - Goueli

Question 1

What are the clinical symptoms of Vitamin C Deficiency?

Answer 1

• Impaired wound healing
• Bleeding ecchymoses
• Swollen gums
• Anemia
• Enlargement and keratosis of hair follicles
• Lethargy
• Depression

Question 2

What is the mechanism of ischemia-reprofusion injury?

Answer 2

• Caused by cytotoxic ROS derived from oxygen in the blood that re-perfuses previously hypoxic cells
  
  • Can occur when tissue is interrupted during surgery or transplantation
• Insufficient O₂ = decreased ATP
• Reduced ATP = increased Na⁺ and Ca²⁺ levels
  
  • The reduced state of electron carriers in the absence of oxygen and loss of mitochondrial ion gradients or membrane integrity leads to increased superoxide production when oxygen becomes available during reperfusion

Question 3

What is the mechanism of Chronic Granulatomatous Disease?

Answer 3

• Phagocytes, neutrophils, eosinophils, & monocytes/macrophages have genetic defects in NADPH oxidase
  
  • defect can occur in any of the four genes that encode for the cytosolic subunits
  • normally microbes are killed by release of antimicrobial granules into the phagosome & the generation of ROS produced by the NADPH oxidase complex
    
    • a.k.a. respiratory/oxidative burst
  • Defective NADPH oxidase function allows survival of the microbes and leads to the formation of a granuloma

Question 4

What does catalase do?

Answer 4

• Catalase protects immune cells from respiratory burst
  
  • reduces hydrogen peroxide to water in peroxisomes (kidney/liver)
  • prevents it from forming the hydroxyl radical in the Fenton reaction or the Haber-Weiss reaction

Question 5

What are the two important Antioxidant defense enzymes?

Answer 5

1. Superoxide dismutase (SOD) removes the superoxide free radical (converts O₂^- → H₂O₂)
2. Catalase and glutathione peroxidase remove hydrogen peroxide and lipid peroxides (H₂O₂ → OH → H₂O)

Question 6

What does Superoxide Dismutase?

Answer 6

• Converts superoxide anion to hydrogen peroxide and O₂
  
  • called dismutation
• Primary defense against oxidative stress because superoxide is a strong initiator of chain reactions
  
  • activity is increased by chemicals and conditions (e.g. hyperbaric oxygen, which increase superoxide production)
  • implicated in familial ALS (5-10% of total ALS)