ROS Flashcards
1
Q
name how ROS formation is enhanced
A
- high oxygen tension, like in supplement oxygen for COPD patients
- hypoxia, carbon monoxide poisoning, ischemic reperfusion
- high levels of acetaldehyde in the liver after ethanol abuse
2
Q
describe function of CoQ in ROS
A
- 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
3
Q
name 3 ways that superoxide is formed
A
- mt during the ETC (CoQ)
- cytosol by microsomal cytochromes P450
- peroxisomes by cytochromes P450
4
Q
describe function of superoxide dismutase (SOD) and where it is found with the cofactors needed
A
- uses 2 superoxides as substrates to form H2O2 and O2
- superoxide dismutase found in:
- extracellular (copper)
- cytosol (copper and zinc)
- mitochondria (manganese)
5
Q
describe the Haber-Weiss rxn and Fenton rxn
A
- Superoxide: Haber-Weiss reaction
- H2O2 + superoxide + H+ =
- OH- (hydroxyl radical) and H2O and O2
- H2O2 + superoxide + H+ =
- Ferrous iron: Fenton reaction
- H2O2 + Fe2+ =
- OH- (hydroxyl radical) and OH and Fe3+
- H2O2 + Fe2+ =
6
Q
describe function of catalase
A
- 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
- H2O2 + H2O2 =
7
Q
describe glutathione peroxidase
A
- 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
8
Q
describe glutathione peroxidase function with membranes
A
- 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
9
Q
name the 3 enzymatic and 3 nonezymatic scavengers
A
- 3 enzymatic:
- SOD
- catalase
- GP
- 3 nonezymatic
- uric acid
- glutathione (released by liver into blood)
- bilirubin
10
Q
describe deficiency of superoxide dismutase (SOD)
A
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
11
Q
name the 3 oxygen dependent enzymes involved in defending the body
A
- 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
12
Q
describe function of NADPH oxidase and myeloperoxidase
A
- 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
13
Q
describe function of myeloperoxidase
A
- 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
14
Q
describe function of nitric oxide in defense
A
- NO formed by macrophages by inducible NO synthase
- Arginine is turned into NO radical by nitric oxide synthase, which is turned into peroxynitrate
15
Q
describe chronic granulomatous disease (CGD)
A
- hereditary NADPH oxidase deficiency
- recurrent severe infections by bacteria (pneumonia) or fungi (aspergillus)
- Less ROS, RNOS and HOCL
