ROS

Question 1

name how ROS formation is enhanced

Answer 1

1. high oxygen tension, like in supplement oxygen for COPD patients
2. hypoxia, carbon monoxide poisoning, ischemic reperfusion
3. high levels of acetaldehyde in the liver after ethanol abuse

Question 2

describe function of CoQ in ROS

Answer 2

• CoQ in the ETC, the one-electron reduced form (CoQH-) is free in the membrane and can accidentally transfer an electron to dissolved oxygen thereby forming superoxide
• Mt DNA is more susceptible to ROS damage than nuclear DNA because it doesn’t have histones and it is close to CoQ

Question 3

name 3 ways that superoxide is formed

Answer 3

1. mt during the ETC (CoQ)
2. cytosol by microsomal cytochromes P450
3. peroxisomes by cytochromes P450

Question 4

describe function of superoxide dismutase (SOD) and where it is found with the cofactors needed

Answer 4

• uses 2 superoxides as substrates to form H2O2 and O2
• superoxide dismutase found in:
  
  • extracellular (copper)
  • cytosol (copper and zinc)
  • mitochondria (manganese)

Question 5

describe the Haber-Weiss rxn and Fenton rxn

Answer 5

• Superoxide: Haber-Weiss reaction
  
  • H2O2 + superoxide + H+ =
    
    • OH- (hydroxyl radical) and H2O and O2
• Ferrous iron: Fenton reaction
  
  • H2O2 + Fe²⁺ =
    
    • OH- (hydroxyl radical) and OH and Fe³⁺

Question 6

describe function of catalase

Answer 6

• catalase is found mainly in peroxisomes and uses H2O2 for detoxification of toxins
  
  • when H2O2 level gets too high in peroxisomes, catalase will degrade H2O2
• catalase contains heme and binds 2 H2O2 as substrates at the same time
  
  • H2O2 + H2O2 =
    
    • 2 H2O and O2

Question 7

describe glutathione peroxidase

Answer 7

• GP needs 2 reduced glutationes (GSH) to act on H2O2
  
  • *selenum is needed as a cofactor*
• H2O2 plus 2 GSH –> GSSG (oxidized glutathione) plus 2H2O

Question 8

describe glutathione peroxidase function with membranes

Answer 8

• GP needs 2 GSH to reverse lipid peroxidation of polyunsaturated FAs in the PM phospholipids
  
  • if peroxidized FAs are not repaired then they will be shortened to smaller segments resulting in leaking of membranes

Question 9

name the 3 enzymatic and 3 nonezymatic scavengers

Answer 9

• 3 enzymatic:
  
  • SOD
  • catalase
  • GP
• 3 nonezymatic
  
  • uric acid
  • glutathione (released by liver into blood)
  • bilirubin

Question 10

describe deficiency of superoxide dismutase (SOD)

Answer 10

Leads to ALS

• 90% of the time the cause is idiopathic, 10% is due to defect of SOD
• deadly degenerative disease of upper and lower motor neurons that control voluntary muscle movement
• symptoms:
  
  • difficulty breathing
  • head drop
  • muscle weakness

Question 11

name the 3 oxygen dependent enzymes involved in defending the body

Answer 11

• NADPH oxidase uses:
  
  • NADPH and O2 to form superoxide
• myeloperoxidase uses:
  
  • H2O2 and Cl- to form hypochlorous acid
• inducible nitric oxide synthase uses:
  
  • NADPH and arginine to form nitric oxide and citrulline

Question 12

describe function of NADPH oxidase and myeloperoxidase

Answer 12

• NADPH oxidase is found in cell membranes of neutrophils
  
  • the enzyme generates superoxide on purpose using molecular oxygen and NADPH (respiratory burst)
• SOD forms H2O2
• Fenton rxn with H2O2 leads to formation of hydroxyl radicals which can break down bacteria

Question 13

describe function of myeloperoxidase

Answer 13

• uses H2O2 and chloride ions as substrates to form hypochlorous acid (bleach) which breaks down bacteria
• MPO leads to the coloration of pus due to 2 heme-like groups

Question 14

describe function of nitric oxide in defense

Answer 14

• NO formed by macrophages by inducible NO synthase
• Arginine is turned into NO radical by nitric oxide synthase, which is turned into peroxynitrate

Question 15

describe chronic granulomatous disease (CGD)

Answer 15

• hereditary NADPH oxidase deficiency
• recurrent severe infections by bacteria (pneumonia) or fungi (aspergillus)
• Less ROS, RNOS and HOCL

Question 16

describe myeloperoxidase deficiency

Answer 16

• recurrent severe infections with candida albicans caused by decreased formation of hypochlorous acid (bleach)
• bacteria are still destroyed by hydroxyl radicals and peroxynitrite as superoxide and nitric oxide are formed
• results in:
  
  • oral and genital infections
  • systemic infections