Reactive Oxygen species ROS + Anti-oxidants Dr. Naif Karadsheh
Oxygen Toxicity & Free Radicals Biradical O 2 Radical O 2 Non-Radical Radical H 2 O 2 OH ROS
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
Reactive Oxygen species (ROS) Generated by : Normal metabolism Environmental factors
Reactive Oxygen species (ROS)
Some Of The Diseases Associated With ROS Injury : Atherosclerosis Respiratory Disease (Emphysema /Bronchitis ) Parkinson s disease Cancer Diabetes Liver Damage Motor neuron disease Aging
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
Oxygen Toxicity and free radicals
Generation of the hydroxyl radical OH
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
Oxygenases : Mono oxygenases (hydroxylases) Dioxygenases Thromboxanes PG leukotrienes Sources of ROS in the cell
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
The main biological targets of ROS Poly Unsaturated Fatty Acids (PUFA) Proteins DNA
Free Radical Mediated Cellular Injury
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
Chain reaction is set via lipid radicals in producing lipohydroperoxides Degradation of peroxidized lipids generating harmful products
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 )
Secondary Antioxidants : A. Dietry : 1. Vitamins Vitamin E ( tocopherol) Vitamin C β-carotenes 2. Other dietary- FLAVENOIDS
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 )
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
Possible Functions of Flavenoids : Inhibition of ROS production e.g. X.O (xanthin oxidase) Free radical scavenger Chelate Fe & Cu Maintenance of Vit E
Flavenoids
Some Flavenoids : Catechins : strawberries, green & black tea Kaempferol : brussel sprouts & apple
Some Flavenoids Quercetin : beans, onions, apples and fruits skin Epicatechin : Cocoa, red wine
Endogenous Antioxidants : Uric acid GSH Melatonin Bilibubin Lipoic acid Ubiquinone (Co, Q10 )
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
Vitamin E : Most widely distributed antioxidant Sole physiological role is to quench free radical reactions.
Fig 21.15. 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.
Compartmentization of free-radical defenses
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