Oxidative Stress Flashcards
What is oxidative stress
A cellular state where increased generation of free radicals is in excess of available antioxidant defences
What are free radicals?
Are molecules with one or more unpaired electrons, are highly unstable and reactive
What are two categories of free radicals?
Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS)
Name 6 examples of free radicals
Superoxide radical Hydroxyl radical Hydrogen peroxide Hypochlorous acid Nitric oxide radical Peroxynitrite
Name five examples of endogenous sources of free radicals
Aerobic respiration Fatty acid oxidation P450 metabolism Phagocytosis Arginine metabolism
Where is >95% of all oxygen metabolised during aerobic respiration?
In complex IV of the mitochondrial electron transport chain
What 2 sites in the mitochondrial electron transport chain have been identified as potential sources for electron leakage?
Complexes I and III
How is phagocytosis a source for free radicals?
During phagocytosis, there is a large increase in O2 uptake by neutrophils and most types of tissue macrophages through activation of an oxidase that reduces oxygen to a superoxide (oxidative burst)
What are some examples of exogenous sources of free radicals?
Air pollution Radiation Cigarette smoke UV exposure Alcohol consumption Anti-cancer drugs Exposure to heavy metals (mercury, lead, cadmium)
What damage do UVB rays cause?
Can induce both direct and indirect effects including DNA damage, oxidative stress, inflammation, premature ageing of skin
What damage do UVA rays cause?
Can lead to generation of free radicals
How does oxidative DNA damage occur?
Can be the result of either a direct (eg sugar, phosphate, purine/pyrimidine bases) and/or indirect attack to DNA (eg radiolysis of H2O, rise of intracellular calcium)
What are some diseases associated with DNA damage?
Arthritis Heart disease Ageing GI disorders Multiple sclerosis Cancer Neurological diseases
What proteins are most at risk of oxidative protein damage?
Those with cysteine and methionine residues, due to their sulphur content
What diseases are associated with protein oxidative damage?
Neurodegenerative diseases Muscular dystrophy Rheumatoid arthritis Respiratory distress syndrome Cataract formation
What does oxidative lipid damage primarily affect?
Membrane associated polyunsaturated fatty acids and cholesterol, induces widespread membrane damage
What diseases are associated with oxidative lipid damage?
CV diseases
Neurological diseases
Rheumatoid arthritis
Cancer
What are antioxidants?
Are the first line of defence against free radical-induced cellular damage
What are the 2 categories of antioxidants and name examples
Enzymatic (eg Superoxide Dismutase, catalase, glutathione peroxidase)
Non-enzymatic (eg Vitamins E and C, selenium, glutathione)
