Reactive Oxygen species ROS + Anti-oxidants. Dr. Naif Karadsheh

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1 Reactive Oxygen species ROS + Anti-oxidants Dr. Naif Karadsheh

2 Oxygen Toxicity & Free Radicals Biradical O 2 Radical O 2 Non-Radical Radical H 2 O 2 OH ROS

3 O 2 Metabolism and Toxicity O 2 Consumption >90% R.C ATP Oxidases Oxygenases Incorporate Oxygen Transfer e- to O 2 & reduced to H 2 O or H 2 O 2 Mono Di 3-5% of consumed O 2 ROS

4 Reactive Oxygen species (ROS) Generated by : Normal metabolism Environmental factors

5 Reactive Oxygen species (ROS)

6 Some Of The Diseases Associated With ROS Injury : Atherosclerosis Respiratory Disease (Emphysema /Bronchitis ) Parkinson s disease Cancer Diabetes Liver Damage Motor neuron disease Aging

7 ROS and Cellular Damage Causes of diseases Contribute to complication of many chronic disease. Proteins, lipids, nucleic acids & Carbohydrates are affected. Most susuptible amino acids Pro, his, arg, Cys, Met..of a.a fragmentation of proteins aggregation proteolytic digestion. Membrane lipids DNA damage e.g strands break

8 Oxygen Toxicity and free radicals

9 Generation of the hydroxyl radical OH

10 Oxidases Sources of ROS in the cell e - + O 2..H 2 O or H 2 O 2 Most oxidases H 2 O 2 Fenton reaction: H 2 O 2 OH Oxidases are confined to sites equipped with protective enzymes

11 Oxygenases : Mono oxygenases (hydroxylases) Dioxygenases Thromboxanes PG leukotrienes Sources of ROS in the cell

12 Coenzymes Q in R.C. Sources of ROS in the cell Respiratory Burst (during phagocytosis,hocl ) O 2, H 2 O 2, OH, NO Ionizing Radiation OH

13 The main biological targets of ROS Poly Unsaturated Fatty Acids (PUFA) Proteins DNA

14 Free Radical Mediated Cellular Injury

15 PUFA PUFA attack LH + OH L + H 2 O lipid free radical LH + O 2 LOO Peroxyl radical PUFA LH+ LOO LOOH + L Lipohydroperoxide another lipid free radical

16 Chain reaction is set via lipid radicals in producing lipohydroperoxides Degradation of peroxidized lipids generating harmful products

17 Cellular Defense Against O 2 Toxicity Primary Antioxidants-antioxidant Enzymes SOD Catalase GSH peroxidase GSH reductase High concentration in liver, adrenal glands & kidney (high content of peroxisomes & mitochondria )

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21 Secondary Antioxidants : A. Dietry : 1. Vitamins Vitamin E ( tocopherol) Vitamin C β-carotenes 2. Other dietary- FLAVENOIDS

22 B. Endogenous antioxidants. C. Repair Mechanism of DNA, oxidized fatty acids & membrane lipids and oxidized amino acids. D. Compartmentation (e,g peroxisomes, ferritin of Fe +2, etc )

23 Flavenoids (polyphenolic Compounds Green tea Chocolate Vegetables as onion, tomatos brocli. Colored fruits as Grapes,blue berries Fruits skin Red wine Flavenoids e.g. quercetin

24 Possible Functions of Flavenoids : Inhibition of ROS production e.g. X.O (xanthin oxidase) Free radical scavenger Chelate Fe & Cu Maintenance of Vit E

25 Flavenoids

26 Some Flavenoids : Catechins : strawberries, green & black tea Kaempferol : brussel sprouts & apple

27 Some Flavenoids Quercetin : beans, onions, apples and fruits skin Epicatechin : Cocoa, red wine

28 Endogenous Antioxidants : Uric acid GSH Melatonin Bilibubin Lipoic acid Ubiquinone (Co, Q10 )

29 Vitamin antioxidants Chain breaking antioxidants terminate free radical lipid peroxidation by : Vitamin E donates single e Cartenoids accept e from lipid Peroxy radicals Vitamin C accepts single e from O 2, H 2 O 2, OH,HOCl, and peroxyl radicals Vitamin C regenerate the reduced form of Vitamin E

30 Vitamin E : Most widely distributed antioxidant Sole physiological role is to quench free radical reactions.

31 Fig Vitamin E Vitamin E terminates free radical lipid peroxidation by donating single electrons to form stable, fully oxidized tocopheryl quinone. Of the eight or more different tocopherols that comprise vitamin E, α-tocopherol, shown here, is the most common in the diet.

32 Compartmentization of free-radical defenses

33 Compartmentization of free-radical defenses Highest activities are in : Liver, adrenal gland & kidney High content of mitochondria, Peroxisomes and Cyt P450 Enzymes in smooth ER SOD and GSH peroxidase are present as isoenzymes

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