WHAT ARE FREE RADICALS? • The most important structural feature of an atom for determining behaviour is the number of electrons in the outer shell. • A substance that has a full outer shell tends not to enter in chemical reactions
“Free radicals are atoms or groups of atoms with one or more odd (unpaired) number of electrons.” • Unpaired electrons cause radicals to be highly reactive. • Even though have unpaired electrons, metals (such as Fe,Cu…) and their ions or complexes with unpaired electrons are not radicals but they help formation of free radicals with catalyse the reactions. • Free radicals may have positive, negative or zero charge.They can be organic or inorganic.
HOW THEY FUNCTION? Atoms always want to be stable. They can do that with 2 ways: • Losing or gaining electron (filling or emptying the outer shell) • Sharing electrons by bounding with other atoms Normally bonds don’t split in a way that leaves molecule with unpaired electron But when weak bond split, free raicals are formed. Free radicals are very unstable and react quickly with other compound to gain electron so they can be stable.
Probably the most well-known free radical, oxygen is the basis for development of most free radicals in the body. Inherently, oxygen is an unstable molecule. Oxygen derived free radicals and H202 are referred to as reactive oxygen species (ROS) Oxygen centered free radicals contain two unpaired electrons in the outer shell.
ENDOGENOUS FREE RADICALS • The most important free radicals in the body are the radical derivatives of oxygen known as reactive oxygen species. • Oxygen derivatives: Superoxide (O2-) Peroxide (H2O2) Hydroxyl Radical (OH.) Single oxygen,(O2 ) nitric oxides • Carbon centered free radicals that arise from attack of an oxidizing radical on an organic molecule. • Hydrogen centered radivals result from attack of the Hydrogen • Sulfur centered radical produce oxidation of glutathione.
e- e-, 2H+ e-, H+ e-, H+ O2 O2- H2O2 OH- H2O H2O Hydrogen peroxide Hydroxyl radical Superoxide
EXOGENOUS FREE RADICALS • Drugs • Radiation • Tobacco Smoking • Inorganic Particles ( asbestos , silica…) • Gases • UV light
FUNCTIONS OF FREE RADICALS • Some free radicals arise normally during metabolism. • Sometimes the immune system produce them to neutralize viruses and bacteria. • Normally body can handle free radicals but if antioxidants are unavailable or if the free radical production excessive damage can occur. • The free radical damage accumulates with age and lead to many age- related diseases.
Free radicals can affect tissues,oxidize lipids proteins and disturb DNA code • Thus they can lead to oxidative stress
Antioxidants • In the aerobic environment, the most dangerous product are the species of reactive oxygen. • The role of antioxidants is to prevent reactive oxygen species’ damage and related diseases • They protect other chemicals of the body from damaging oxidation reactions by binding together with free radicals and other reactive oxygen species (H202,O2)
During this reaction the antioxidant sacrifices itself by becoming oxidized. • However, antioxidant is not unlimited.One antioxidant molecule can only react with one free radical or other ROS • Therefore, we need to get antioxidant resources constantly.
According to their location Plasma antioxidants: ascorbic acid (Vitamin C), bilirubin, uric acid, transferrin, ceruloplasmin, β-carotene; b) Cell membrane antioxidants: α-tocopherol (Vitamin E) c) Intracellular antioxidants: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) ANTIOXIDANT TYPES
According to their nature and action • Enzymatic antioxidants: • SOD, catalase, GPx, glutathione reductase b) Non-enzymatic antioxidants: • Nutrient antioxidants: • β-carotene, α-tocopherol, ascorbic acid, • Metabolic antioxidants: • bilirubin, uric acid, ceruloplasmin, ferritin, transferrin, albumin, glutathione
Superoxide Dismutase (SOD): Firstly ,SOD catalyses the conversion of O2 to H2O2 and H2O Catalase: then it converts H2O2 to H2O and O2 Glutathione Peroxidase: it reduces H2O2 to H2O ENZYMATIC ANTIOXIDANTS
GSH Peroxidase and reductase • Then oxidized glutathione reduced by glutathione reductase O2•¯ H2O2 H2O + O2 SOD Catalase
These enzymes repair DNA, turn the proteins previous form and break down oxidized lipids • These enzymes also require trace metal cofactors for maximal efficiency, including selenium for glutathione peroxidase; copper,zinc or manganase for SOD; and iron for catalase
THE NONENZYMATIC ANTIOXIDANTS • This includes • the lipid-soluble vitamins; vit E and vit A or beta carotene • the water soluble vit C • Glutathione(GSH), a tripeptide molecule. enzymatic and nonenzymatic antioxidants are working together.
OTHER ANTIOXIDANTS • Glutathione(GSH) • CoQ10 (Coenzyme Q10) • Selenium • Albumin • Plasma Proteins ( ceruloplasmin and transferrin) • Melatonin ( once oxidized cannot be reduced to former state thus referred to as terminal antioxidant) *endogen* • Uric acid (high levels act as prooxidant) *endogen* • Drugs
EXCESSIVE ANTIOXIDANTS • Antioxidants that are reducing agents can also act as pro-oxidants (oksidasyon hizlandirici) when got excessive with supplements