Oxidative Stress and Antioxidants Flashcards
What are free radicals
Any atom, molecule or ion that contains one or more unpaired electrons and is capable of independent existance
What are the species in the Reactive Oxygen Species group
Superoxide
Hydrogen peroxide
Hydroxyl radicals
Name some endogenous sources of biological radicals
Electron transport chain
Peroxidases
Nitric oxide synthases
NADPH oxidases
Name some exogenous sources of biological oxidants
Radiation
Pollutants
Drugs
Toxins
How are free radicals produced
Produced by ionising radiation
What are the types of damage caused by ROS
DNA - can react with either base (mispairing and mutation) or sugar (strand break and possible mutation on repair)
Proteins - reacts with side chains (change in protein structrue) or with protein backbone (cause fragmentation and degradation)
Lipids - lipid peroxidation (process significant in aetiology of atherosclerosis)
What specific residue can a ROS react with and why is this important
Can react with cysteine residue by taking away an electron
Leads to inappropriate disulphide bond formation causing misfolding, crosslinking and protein dysfunction
What type of RBC can form as a result of oxidative stress
Heinz bodies due to precipiated cross-linked Hb
How does an ROS react with a lipid in the lipid membrane
ROS reacts with polyunsaturated fatty acid forming lipid radical
This reacts with oxygen to form lipid peroxyl radical which reacts with nearby fatty acids to cause a chain reaction
Hydrophobic environment of bilayer disrupted and membrane integrity eventually fails
What defence mechanisms are in place to defend against ROS
Superoxide dismutase/catalase
Glutathione
Free radical scavengers
How does superoxide dismutase/catalase defend against ROS
Superoxide dismutase catalyses conversion of superoxide to hydrogen peroxide and oxygen
Catalase breaks down hydrogen peroxide to molecular oxygen and water
How does glutathione defend against ROS damage
GSH is a tripeptide, synthesised as an antioxidant
Thiol group of Cys residue in GSH donates an electron to the ROS and reacts with another GSH to form a disulphide bond (GSSG) - reaction catalysed by glutathione peroxidase (requires selenium)
Oxidised glutathione (GSSG) reduced back by glutathione reductase which catalyses transfer of electrons from NADPH to the disulphide bond of GSSG
How do free radical scavangers defend against ROS damage and what are they
They are Vitamins C and E, along with carotenoid, flavenoid, melatonin
They reduce ROS damage by donating a hydrogen atom and electron to free radicals in nonenzymatic reaction
Vit E is lipid solube, protects against lipid peroxidation
Vit C regenerates reduced form of Vit E
What is oxidative stress
Where the production of ROS is excessive or the levels of antioxidants are low so cells cannot cope with the ROS
What is the respiratory burst
Where there is a rapid production and release of ROS to destory bacteria or fungal cells
Done by cells of immune system like neutrophils and monocytes
Is produced by NADPH oxidase (membrane-bound complex) which is present in membrane of phagosomes and it transfers electrons from NADPH across membrane to molecular oxygen to generate superoxide
Superoxide combines with Cl- forming hypochlorite, and combines with nitric oxide to form peroxynitrite. Both then destory the pathogen
