Expansion
Unpaired electrons attacking lipids, proteins and DNA
Expansion
Sources
- Normal metabolism: leakage from the electron transport chain
- Inflammation: the neutrophil respiratory burst, using NADPH oxidase and myeloperoxidase
- Ionising radiation, ultraviolet light
- Drug metabolism: paracetamol (NAPQI), carbon tetrachloride
- Transition metals: iron and copper, through the Fenton reaction
- Reperfusion after ischaemia
Three targets
- Lipids: lipid peroxidation of membranes, a self-propagating chain reaction
- Proteins: cross linking, misfolding, loss of enzyme function
- DNA: strand breaks and base modification, causing mutation and malignancy
Defences
- Enzymes: superoxide dismutase, catalase, glutathione peroxidase (which needs selenium)
- Antioxidants: vitamins C and E, glutathione, beta carotene
- Metal binding proteins: transferrin, ferritin, caeruloplasmin, which keep iron and copper unavailable
“Free radicals explain the toxicity of paracetamol, the damage of reperfusion, and the mutagenicity of radiation.”
Chronic granulomatous disease demonstrates the other side: failure of NADPH oxidase means neutrophils cannot generate the burst, so catalase positive organisms survive and cause recurrent abscesses.