Free Radicals Flashcards
4 types of free radical reactions
Hydrogen abstraction
Addition
Termination
Disproportionation
How are ROS produced endogenously (5)
Respiratory chain Immune system activity Cytochrome P450s Auto-oxidation of biomolecules Enzymes with free radicals as intermediates
Exogenous ROS production (5)
UV radiation Environmental pollutants Tobacco smoke Pesticides Drugs
Why are most radicals called ROS?
As they are derived from oxygen
Respiratory chain and ROS (3)
Most of oxygen uptake is utilised by ETC
oxidation of nutrients feeds electrons into chain
Leakage of free radicals is a by-product if this process
Name the key points of leakage in the ETC (3)
Complex I
Ubiquinone-complex III
Complex IV
Define free radicals (2)
Unstable molecules with unpaired electrons
Free radicals are highly reactive and will react with other molecules in order to stabilise them
Examples ROS free radicals (6)
Superoxide Hydroxyl Hydroperoxyl Peroxyl Carbonate Carbon dioxide
Examples of ROS non-radicals (5)
Hydrogen peroxide Ozone Peroxynitrite Peroxynitrous acid Organic peroxides
Mitochondria is the richest sources of which ROS?(2)
Superoxide
Hydrogen peroxide
Which macronutrient is most vulnerable for ROS mediated injury?
Lipids
Why are PUFA attractive targets for ROS?
Electron density of double bonds
Effects of lipid peroxidation
Damage to cell and organelle membranes
Effects of ROS on protein (4)
Changes in : 3D protein structure Enzyme active sites Receptor binding sites Transport functions
ROS injury on nucleic acids (DNA) (3)
May cause strand scission
This is cleaving of sugar-phosphate backbone
May alter bases
What can un-repaired DNA damage lead to (2)
Mutation
This is the molecular basis of cancer
What causes oxygen toxicity?(3)
The formation of ROS
Through endogenous processes
Additional environmental burden increases exposure
What are antioxidants?
Molecules which produce termination reactions with free radicals
3 classes of antioxidants
Scavenging antioxidants
Antioxidant enzymes
Proteins with non-enzymatic AOX properties
What scavenging antioxidants?(3)
Molecules which react with ROS to form stable products
They end chain reaction in biological systems
They are converted to non-AOX species
Where are scavenging antioxidants located?(2)
Biological fluids
Cells and organelle membranes
Water soluble scavenging antioxidants (2)
Ascorbic acid
Uric acid
Fat soluble antioxidants (5)
Carotenoids Tocopherols Polyphenols Flavonoids Anthocyanins
Which type of scavenging antioxidants is more important in health?
Fat soluble
Where are fat soluble antioxidants found?(3)
Membranes
Lipoproteins in circulation
Adipose tissue
Which type of scavenging antioxidant can be stored?
Fat soluble
How is uric acid formed?
From the metabolism of purine
Consequences of high levels of uric acid?(2)
Gout
Kidney stones
Examples of polyphenols (2)
Tannins
Gallic acid
Examples of flavonoids (2)
Catechins
Resveratrol
What are antioxidant enzymes?
Enzymes which exist to remove ROS
What do most antioxidant enzymes have at catalytic centre?
Metal ions
Metals associated with antioxidant enzymes (4)
Copper
Zinc
Manganese
Selenium
What happens to the majority of DNA damage
It is repaired
What can un-repaired DNA damage lead to (2)
Mutation
This is the molecular basis of cancer
Examples of antioxidant enzymes (2)
Superoxide dismutase
Catalase
The role of superoxide dismutase (2)
Catalyses the conversion of superoxide radials to hydrogen peroxide
Critical in quenching ROS formed in respiration
Isoforms of superoxide dismutase (3)
Copper
Zinc
Manganese
Role of catalase
Converts hydrogen peroxide to water and oxygen
Where is catalase located?
Peroxisomes
What is glutathione?
Tripeptide
Which AAs does glutathione consist of?
Glutamate
Glycine
Cysteine
Explain the glutathione system (4)
Reduced glutathione (GSH) is the substrate for glutathione peroxidase
GPx uses selenium to reduce hydrogen peroxide
GSH is oxidised in process to oxidised glutathione
Which can be regenerated by glutathione reductase
Albumin is the most _____ blood plasma protein. It accounts for ____ of protein in circulation
Abundant
60%
Where is albumin produced?
Liver
How does albumin reduce oxidation?
It contains several AAs that can react with free radicals
Free forms of which metals can cause free radical generation?(2)
Iron
Copper
How can free radical generation of free irons be prevented?
Binding to protein
Which proteins can free irons bind to in order to prevent free radical generation?(4)
Ferritin
Lactoferrin
Transferrin
Ceruloplasmin
What are the two forms of periodontal disease?
Gingivitis (50% of population) Destructive periodontitis (10-15% of population)
How does periodontitis increase risk factors for CVD?(3)
Increases:
Leukocytes
Clotting factors
Pro-inflammatory cytokines
What is periodontal disease initiated by?
Bacteria
Salivary antioxidants (3)
Uric acid
Ascorbic acid
Albumin
Gingival crevicular fluid antioxidant
Glutathione
The immune system and ROS (4)
Respiratory burst involves greater oxygen uptake by cell
And faster glucose utilisation to generate NADPH
NAPDH oxidase generates superoxide
Which breaks down to form longer-acting oxidants
How are free radical detected?
Through their effects in biological systems
ROS injury on proteins (3)
Causes proteins to:
Cross-link
Aggregate
Fragment
Examples of AAs targets for free radical attack (4)
Cysteine
Methionine
Phenylalanine
Tyrosine
Conditions where ROS plays a major role in disease (4)
Cancer
CHD
COPD
Type 1 diabetes
Conditions where ROS contributes to the progression of condition (3)
Periodontitis
Ageing
Neurodegeneration
Potential negative effects of antioxidant supplements (5)
High dose may be excreted with no benefit
High dose may lead to pro-oxidant effect
Metabolism of the antioxidant may prevent benefit
Supplementation dose may not reach target tissue
High concentrations may enhance disease progression through non-ROS related mechanisms
What can the immune system use free radicals for?
Destroy pathogens
Immune system produces free radicals via ______ _____
Respiratory burst
