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Free radical and antioxidants
- 2. Learning Objectives • What is respiratory burst? • What is free radical and ROS? • How free radicals are generated? • What are the types of free radicals? • Examples of free radicals. • Properties of free radicals. • Effects of free radicals. • What is Anti oxidants? • Types of Anti oxidants. • Functions of Antioxidants. • Oxidative stress • Effects of oxidative stress on health. • Diagnostic stress markers • Stress busters.
- 3. We know oxygen is required for metabolism and health But do we required in these forms for health?
- 4. Electron Transport Chains Two types Mitochondrial Electron Transport Chain Microsomal Electron Transport Chain Phosphorylating Non-phosphorylating Participate in ATP formation Participate in Hydroxylation and desaturation NAD-FAD-Fe+2 NADPH- Cyt-P450 Reduced Fe(II) CytP450 complex react with O2 to form 1. H2O 2. O’ added to Organic substrate - [O’ + H+ OH]
- 5. What is Respiratory burst? Rapid release of ROS, Super oxide anion, O2’, H2O2 Normally They are utilised for immunological defence, cell signalling and fertilization in Animal Essential for degradation of internalized bacteria/ pathogen [innate immunity] RB increases 10 to 20 fold oxygen consumption NADPH oxidase generate SO from oxygen in phagocytes Phagocytic cell use this for killing Bacteria, Toxin
- 6. Glucose NADPH NADP+ + H+ NADPH oxidase Respiratory Burst Phagocytes HMP Shunt SOD MPO Respiratory Burst – Bactericidal activity MPO – Myeloperoxidase in polymorphs Cl e-
- 7. BUT Leading cause of death • Heart disease – 32 to 45% • Cancer – 23 to 30% • Strokes – 07 to 10% • Renal diseases – 20 to 40% • Lung disease, Pneumonia, Asthma, • Diabetes mellitus, Liver disease, • Neurodegenerative disease [PD, AD, MS] >90% disease incidences involve FREE RADICAL DAMAGE
- 8. What is stable atom? An Atom having octet electronic configuration in their outer most orbit Inert Gases
- 9. What is free radicals? An atom having unpaired electron in outer most orbit
- 10. What is free radicals? • Any molecule having one or more unpaired electrons • Highly unstable and chemically reactive • Free radicals – ROBBERS • They are Deficient in energy • They attack and snatch energy from the other cells to satisfy themselves
- 11. What are the types? • Free Radicals are Mainly of three types • Reactive oxygen species [ROS] • Reactive Nitrogen species [RNS] • Reactive metabolites and intermediates
- 12. Examples of free radicals Reactive oxygen species Reactive Nitrogen species Super oxide O2 - Nitric oxide NO’ Hydrogen peroxide H2O2 Peroxy nitrite ONOO’ Hydroxyl radical OH- Singlet Oxygen -O2 Reactive metabolite Hydroperoxyl radical HOO- Lipid peroxide radical ROO-
- 13. Source of free radicals Endogenous Exogenous Immune cell activation Air and Water pollution Lipid peroxidation Tobacco smoking Arginine metabolite, Oxidation of Heme Alcohol consumption Mental stress Exposure to heavy metal toxins Infection, Inflammation Drugs and medication Ischemia Radiation and UV light Cancer
- 14. How free radicals are generated? Most free radicals in biological system are derivatives of Oxygen [ROS] Derivatives of Nitrogen [RNS], Reactive metabolites or intermediates Fenton Reaction Fe/ Cu
- 15. Properties of free radicals 1. Unstable 2. Highly reactive 3. Having very short life 4. Generates new free radicals by chain reaction 5. Cause damage to biomolecules, cell and tissue • Have two fold job, When in balanced state -helpful When [loose balance] unbalanced-damage cell Functions of free radicals
- 16. Harmful effects of free radicals 1. Damage bio-membrane [lipid peroxidation] 2. Protein oxidation loss of protein function. 3. Damage to Glycation effect on receptors and signalling 4. DNA damage mutation and cancer
- 18. What is Anti-oxidants? Definition: Compounds that inhibit oxidation and prevent the ill effect of free radicals. Free Radical Anti-oxidant A Compound that donate electron to free radical and make them stable
- 19. Types of Anti-oxidants Glutathione peroxidase Vitamin E Selenium Glutathione Catalase Vitamin C Zinc Uric acid Superoxide dismutase Beta Carotenoids Copper Bilirubin peroxidase Vitamin A Iron Ceruloplasmin Lactoferrin Alpha lipoic acid Transferrin Heptoglobin Enzymes Vitamins Minerals Metabolites
- 20. Types based on action of Anti-oxidants 1. Scavenging or Primary Anti-oxidants Vitamin E, Vitamin C, Carotenoids, Uric acid, Polyphenols, Flavanoids 2. Preventive or Secondary Anti-oxidant SOD, Peroxidase, Catalase, Lactoferrin, Carotenoids, 3. Repair Anti-oxidants Glutathione,
- 21. Functions of Anti-oxidants 1. Boost immune system 2. Protect against the effect of carcinogen 3. Neutralize ROS 4. Protect from oxidative damage to genetic material [DNA]
- 22. Oxidative stress Lungs Asthma Chronic bronchitis Kidneys Glomerulonephritis Chronic Renal failure Brain Depression, Stroke Memory loss, AD, PD Bone Rheumatism Arthritis Eyes Cataract Retinal disease Heart & blood vessels Hypertension Arteriosclerosis Ischemia, Cardiomyopathy Aging Cancer DM Inflammation
- 23. Oxidative stress markers. • Direct markers • Lipid peroxidation [LPO] • Thiobarbituric acid reactive substances [TBARS], Malondialdehyde [MDA] • Isoprostane • Protein carbonyl [PC] Indirect Markers • SOD • Catalase • Glutathione reductase • Glutathione peroxidase • Glutathione s transferase • Vitamin -E, C, A
Editor's Notes
- Coloured fruits and vegetables contains lots of antioxidants. Beta- carotene, Lycopene, Lutein, Ascorbic acid and selenium, Zinc.
- Oxygen is required for oxidation of food and generation of energy. Electrons released during the process of oxidation ultimately accepted by Oxygen. Four electrons as required to convert O2 to H2O [Reduction of oxygen]. Some times incomplete reduction of oxygen results in Oxygen free radical [ROS]. This may be due to leak of electrons from ETC or excessive oxygen.
- Major consumer of oxygen in our body are Electron Transport chain in mitochondria which generates ATP. 2. Microsomal Electron Transport chain which helps in disinfecting the cell and detoxifying debris from the cell.
- Respiratory burst - The increase in cell metabolism and oxygen consumption, which is coupled with the release of reactive oxygen species (ROS). Phagocytic cell have master this mechanism for their benefit. Mitochondria some times use excess oxygen but can partially reduce them leading to ROS formation.
- Normal bactericidal effect of cell, Detoxication of ingested drugs and toxic chemicals, Fragmentation of worn-out proteins.
- Free radicals are normally produced in human body as one of the defence mechanisms. Their balance is maintained by antioxidants. But, when production of Free radical increases beyond the neutralizing capacity of antioxidants; oxidative stress result. Oxidative stress is the mother of almost all diseases like CHD, DM, Cancer, Respiratory diseases, Cataract, Male infertility, Parkinson’s, Alzheimer's disease. Aging is also associated with oxidative stress.
- In nature, except inert gases, no element have completely paired electronic configuration. This is the reason we get millions of chemical compounds. When two or more elements come together to share their electrons in order to complete octet in their outermost valence shell they become stable. As far as outer most valence shell has unpaired electrons it is unstable and called free radical.
- Free radical means atom having unpaired electron. ROS does not always means the same because H2O2 and singlet oxygen [O2] do not contain unpaired electron but they are reactive.
- Every one/atom wants to settle/ stabilise. It may be by beg, borrow or steal technique. Free radical do the same.
- The Fenton reaction describes the formation of hydroxide (OH−) and hydroxyl radical by a reaction between Iron (II) (Fe2+) and hydrogen peroxide (H2O2). Haber–Weiss reaction is where hydroxyl and hydroxide ions are generated from the reaction of H2O2 and superoxide ion ( O 2 • − ) catalysed by iron. Fenton reaction, generation of the superoxide radical and the hydroxyl radical involve iron and copper.
- Free radicals try to snatch electron from fatty acid of cell membrane. The next fatty acid will get oxidised in sequence causing chain reaction.
- Free radicals try to snatch electron from fatty acid of cell membrane. The next fatty acid will get oxidised in sequence causing chain reaction. Glycation of carbohydrate result on adversely on signalling and receptor function. Damage caused on nucleic acid cause mutation and carcinogenesis. Fatty acid oxidation increases malondialdehyde and cojugated diene. Lipid peroxidation is identified as basis of pathogenesis. Lipid hydroperoxide and cytotoxic and cause extensive damage to enzyme and embrane. Effect on protein is of three type 1. fragmentation 2. Aggregation 3. Proteolytic digestion. Fragmentation cause change in protein structure and immunological reactions. [Auto immunity]
- Antioxidants – They scavenge free radical there by reduce or inhibit oxidation. They are naturally produced in our body. Also we consume then in our diet.
- Antioxidants may be classified based on their biochemical nature as 1. Enzymes 2. Vitamins 3. Minerals 4. Metabolites Alternatively they are classed base on their presence in the cell as 1. Plasma antioxidants 2. membrane bound antioxidants 3. Intracellular antioxidants.
- Based on their biological activity antioxidants may be classified as; 1. Primary antioxidants or Scavenger - The primary antioxidants, also called chain-breaking antioxidants, as they are able to react directly with free radicals by transforming them to more stable, non-radical products. They function as free radical terminators. 2. Secondary or Preventive antioxidants- The secondary or preventive antioxidants work indirectly on limiting lipid oxidation. Several mechanisms including the chelation of transition metals, singlet-oxygen quenching and oxygen scavenging can be exhibited by secondary antioxidants. They act as inhibitors of free radical oxidation reactions. 3. Repair antioxidants- they manage to repair the damage caused by free radical. Example DNA repair, Glutathione
- Increased production of free radicals or decreased activity f antioxidant system leads to Oxidative stress. It is involved in many pathological conditions. CVDs, Atherosclerosis, hypertension, Asthma are well known examples.