WEEK 7- FREE RADICALS Flashcards
What are free radicals
- to be stable must have paired electrons
- will create a chained reaction
endogenous reaction
- Metabolic processes requiring oxygen produce ROS e.g. oxidative phosphorylation in mitochondria (high energy diets) - Enzymatic oxidation - Exercising - Inflammation - Obesity
exogenous reaction
- Radiation
- Smoking
- Dietary components: which?
- Cooking by-products
- Air – water pollution
- Exposure to pesticides solvents, environmental toxins, drugs
- Ion metal transition
Antioxidant defence system
Two main principles of antioxidant activity:
1- Chain breaking mechanisms by donating electrons to the free radicals.
2- Removal of ROS/reactive nitrogen species by quenching the chain initiating catalyst.
Mechanisms include: electron donation, metal ions chelation, radical scavenger, hydrogen donor, peroxide decomposer, singlet oxygen quenchers, enzyme inhibitors, synergist, metal chelators, gene expression regulation.
There are two systems in the antioxidant defense: enzymatic and non-enzymatic, with both including endogenous and exogenous components.
non-enzymatic antioxidant system
Non-enzymatic antioxidant system:
- Vitamin E: removes free radical intermediates and prevents propagation reaction to continue. Produces oxidised alpha tocopheryl radicals that can be recycled through reduction by other antioxidants (ascorbate, retinol, ubiquinol) to its active form.
- Ascorbic acid: is maintained in reduced form by reaction with glutathione. Reduces and that neutralises ROS: e.g. hydrogen peroxide. Also a substrate for the antioxidant enzyme ascorbate peroxidase
- Glutathione: most important cellular antioxidant, maintains the redox status the cells. Formed from cellular cysteine. Thiol group in cysteine is a reducing agent. Kept in reduced form in cells by glutathione reductase. Reacts directly with oxidants and reduces metabolites.
- Bilirubin, albumin, and thiols are hydrophilic radical and vitamin E and ubiquinol are lypophillic radical scavengers.
- Uric acid = 50% of antioxidant ability of plasma.
- Melatonin crosses cell membranes and BBB. Once oxidised cannot be reduced to its former state because forms end - products with free radicals. ( = “suicidal antioxidant”)
Enzymatic antioxidant system
- Products of gene expression
- Superoxide dismutase converts superoxide (e.g. from oxidative phosphorylation) to hydrogen peroxide.
- SOD1: Cu and Zn dependent - SOD2: Mn dependent
- SOD3: Fe dependent
- Catalase converts hydrogen peroxide to water and oxygen. Present in every organ, but especially in liver.
- Glutathione enzyme system: reductases, peroxidases (= GPX - Se dependent) and S-transferases.
- GPX has four different isoenzymes: catalyses the breakdown of hydrogen peroxides and hydro-peroxides
non-enzymatic
Plasma constituents: bilirubin, uric acid, melatonin, albumin, glutathione
Food constituents:
– Vitaminsandminerals
• Electrons donors
• Co-factors in the
enzymatic system
– Phytochemicals:lycopene,B- carotene, flavonoids, epicatechins, resveratrol etc.
• Mild electron donors
• Act as signals for gene transcription of antioxidant enzymes
enzymatic
Gene products that function as enzymes:
- Catalases, superoxide dismutase, glutathione
peroxidase, hemoxygenase etc…
- Deactivate or lyse free radicals. E.g.: conversion to water and oxygen
- Require co-factors for function: zinc, copper, iron, manganese, selenium
enzymatic antioxidant defense system up-regulation
- Nrf2 is a transcription factor that signals the expression of genes for antioxidant enzymes
- Nrf2 is activated when there is an increase in free radicals (e.g ROS) in the cell, and by certain phytochemicals
- When activated, it moves to the nucleus when it binds to the antioxidant response element, where it promotes the expression of antioxidant enzymes
- more in slides
antioxidanat capacity
Defines the synergistic work between the endogenous and the exogenous, enzymatic and non-enzymatic antioxidant systems in keeping free radicals in equilibrium
Redox homeostasis
= balance between pro and antioxidants
