• 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:

1. Losing or gaining electron (filling or emptying the outer shell)

2. 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.

TYPES: ENDOGENOUS AND EXOGENOUS FREE RADICALS

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.

O2

e-

O2-

e-, 2H+

H2O2

e-, H+

OH-e-, H+

H2OH2OSuperoxide Hydrogen

peroxideHydroxyl radical

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

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.

ANTIOXIDANT TYPES

According to their locationa) 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)

According to their nature and action

a) 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

ENZYMATIC ANTIOXIDANTS1. Superoxide

Dismutase (SOD): Firstly ,SOD catalyses the conversion of O2 to H2O2 and H2O

2. Catalase: then it converts H2O2 to H2O and O2

3. Glutathione Peroxidase: it reduces H2O2 to H2O

• Then oxidized glutathione reduced by glutathione reductase

O2•¯ H2O2 H2O + O2

Catalase

GSH Peroxidase

and reductase

SOD

• 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

1. the lipid-soluble vitamins; vit E and vit A or beta carotene

2. the water soluble vit C

3. Glutathione(GSH), a tripeptide molecule.

enzymatic and nonenzymatic antioxidants are working together.

ANTIOXIDANT VITAMINS (antioxidants taken with diet)

Vitamin E

(alpha tocopherol)

Breaks lipid peroxidation

Scavenges lipid peroxide O2 and OH

Fat soluble

Beta carotene Prevent oxidation of vit A

Scavenges OH O2 and peroxy radicals

Fat soluble

Vitamin C

(ascorbic acid)

Scavenges OH O2 and peroxy radicals

Neutralize oxidants

Water soluble

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 terminal antioxidantantioxidant) *endogen*

• Uric acid (high levels act as prooxidant) *endogen*

• Drugs

DIETARY SOURCES

EXCESSIVE ANTIOXIDANTS

• Antioxidants that are reducing agents can also act as pro-oxidants (oksidasyon hizlandirici) when got excessive with supplements