Oxygen toxicity Flashcards
Explain oxygen’s reactivity?
Favour reduction single electron
2 unpaired electrons
Highly reactive
Explain reactive oxygen species (ROS)?
Highly reactive oxygen containing compounds Free radicals- single unpaired electron in orbital
OR
Compounds readily converted to oxygen free radicals in cell
Compounds contribute to ageing, homeostasis and some cancers.
What do ROS cause?
Ageing
Homeostasis
Cancers
Name 3 exogenous sources of ROS?
UV radiation
Tobacco
Drugs
Name 2 endogenous sources of ROS?
NADPH
Electron transport chain
What is the most potent ROS?
Hydroxyl radical
Formation of radicals
Oxygen reduced by single electron form superoxide
Superoxide further reduced form hydrogen peroxide
Hydrogen peroxide reduces produce hydroxyl free radical
Further reduced produce water
Is hydrogen peroxide a radical, soluble?
Not radical but is ROS
Easily converted hydroxyl radical (OH-)
Lipid soluble- cause damage away site of formation
What catalyses the formation of hydroxyl radical from hydrogen peroxide?
Fe2+, Cu2+
What processes changes hydrogen peroxide into hydroxyl radical?
Fenton reaction- iron dependent
Donate single electron
Haber Weiss also forms hydroxyl radical
Write Fenton reaction?
Write Haber-Weiss equation?
Write Haber-Weiss cycle?
4 Reactions combine to produce OH. and consume H2O2
What is the most potent ROS?
Hydroxyl radical
Initiator chain reactions form lipid peroxides
Why is hydroxyl radical dangerous?
Lipid soluble- cause damage away from site formation and damage lipid barriers
What is a respiratory burst?
Immune system defense against bacteria
Sudden release ROS by immune cells during phagocytosis (neutro, macro, monocytes)
What is the process of respiratory burst?
Immune cells use NADPH oxidase to reduce oxygen to superoxide
Superoxide released
Superoxide further reduced hydrogen peroxide
Reduced again to hydroxyl radical- generate ROS
Neutrophils and monocytes use myeloperoxidase combine H202 with Cl- produces hypochlorite
H202+Cl- forms H20 + Cl-
What is function of hypochlorite?
Damage bacterial cell membranes
Destroy bacteria
What occurs if absence of NADPH oxidase?
Prevent formation ROS
Cause chronic granulomatous disease
Build up of pathogens in phagocytes
Can engulf not kill
Lead skin infections
How is the body protected against oxygen toxicity?
Antioxidant enzymes
Antioxidant vitamins
Cellular compartmentalisation
How do antioxidant enzymes protect body?
Superoxide dismutase
Convert superoxide to hydrogen peroxide (non-toxic) and oxygen
Catalase
Catalyses conversion hydrogen peroxide to water and oxygen
Protect white blood cells against own resp burst
Glutathione Peroxidase
Catalyses reduction hydrogen peroxide to water and disulphide
What enzyme protects white blood cell against own respiratory burst?
Catalase
How do antioxidant vitamins protect the body?
Vit E- found liver
- free radical scavenger
- protect against lipid peroxidation
- terminate free radical propagation in
membranes
Vit C- ascorbic acid
- react with superoxide and hydroxyl
radical
- regenerates reduced vit E
How does cellular compartmentalisation protect the body?
Resp burst only in phagosomes
Harmful chemicals can’t exit and damage healthy tissue
What do free radicals damage? and result?
Proteins, lipids, carbohydrates, nucleic acid
Membranes of: cell, nuc, mito, ER
Cell membrane damage- increased permeability membrane- influx Ca, H20, Na
Changes electrical gradient- cell function
Damage DNA- strand break and mutations
What are diseases associated with free radical damage?
Emphysema
Parkinson’s
Diabetes
Acute renal failure
