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Antioxidant Enzymes and

Human HealthBy

Muhammad Z. Naji

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• An antioxidant is a molecule that inhibits the oxidation of other molecules.

• Oxidation is a chemical reaction that can produce free radicals, leading to chain reactions that may damage cells.

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Free radicalsFree radicals• Is a highly reactive compounds form

during normal metabolic functions and may be introduced from the environment.

• These molecules are unstable because of lone pair of electrons make it become highly reactive.

• They react with cellular molecules such as proteins, lipids and carbohydrates, and denature them. RISK

• As a result of this, vital cellular structures As a result of this, vital cellular structures and functions are lost and resulting a and functions are lost and resulting a pathological conditions.pathological conditions.

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• The main role of antioxidant enzymes are stabilizing, or deactivating free radicals before they attack cellular components.

• They act by reducing the energy of the free radicals by giving up some electrons to become stable

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• Many studies shows causes by more than sixty different health conditions, including the aging process, cancer,diabetes, Alzheimer’s disease, strokes, heart attacks and atherosclerosis.

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Free radicals and their scavengers

• Free radicals are electrically charged molecules, i.e., they have an unpaired electron, which causes them to seek out and capture electrons from other substances in order to neutralize themselves.

• Oxygen is a highly reactive atom that is capable of becoming part of potentially damaging molecules commonly called free radical or reactive oxygen species (ROS).

About 5% or more of the inhaled O2 is converted to ROS such as superoxide,hydrogen peroxide, and hydroxyl radicals by univalent reduction of O2.

• This antioxidant system includes :-• antioxidant enzymes:- (SOD, and reductase,

etc.),• nutrient-derived antioxidants:- (ascorbic acid,

tocopherols and tocotrienols, carotenoids),• metal binding proteins:- (ferritin, lactoferrin,

albumin, and ceruloplasmin) • and numerous other antioxidant phytonutrients

present in a wide variety of plant foods

• Reactive Oxygen Species:-Reactive oxygen species (ROS) is a term that encompasses all highly reactive, oxygencontaining molecules, including free radicals

• Types of ROS includethe hydroxyl radical, the superoxide anion radical, hydrogen peroxide, singlet oxygen, nitric oxide radical, hypochlorite radical, and various lipid peroxides

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Pathways of ROS generation:-Pathways of ROS generation:-• A consequence of normal aerobic metabolism: A consequence of normal aerobic metabolism:

approximately 90% of the oxygen utilized by approximately 90% of the oxygen utilized by the cell is consumed by the mitochondrial the cell is consumed by the mitochondrial electron transport system.electron transport system.

• Oxidative burst from phagocytes (white blood Oxidative burst from phagocytes (white blood cells) as part of the mechanism by which cells) as part of the mechanism by which bacteria and viruses are killed, and by which bacteria and viruses are killed, and by which foreign proteins (antigens) are denatured.foreign proteins (antigens) are denatured.

• Xenobiotic metabolism, i.e., detoxification of Xenobiotic metabolism, i.e., detoxification of toxic substances.toxic substances.

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Consequences of generation of ROS

• O2 can behave like a radical (a diradical) owing to presence of two unpaired electrons of parallel spin Its electronic structure result in formation of water by reduction with four electrons, i.e.:

O2 + 4H+ + 4e- 2H2O

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• O2 undergoes reduction, several reactive• intermediates are formed, such as

superoxide (O2-), hydrogen peroxide (H2O2),

and the• extremely reactive hydroxy radical (°OH):

collectively termed as the reactive oxygen• species, the process can be represented as:

Finally, for the production of reactive hydroxy radical ºOH, except during abnormal exposure to ionization radiation,generation of ºOH in vivo requires the presence of trace amount of H2O2 and Fe2+ salt formsºOH, as given following reaction :

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Antioxidant protection systemTo protect the cells and organ systems of the

body against reactive oxygen species (ROS), humans have evolved a highly complex antioxidant protection system. It involves a variety of components, both endogenous and exogenous in origin,

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A.A. Endogenous AntioxidantsEndogenous Antioxidants

BilirubinBilirubin Thiols, e.g., glutathione, lipoic acid, N-acetyl Thiols, e.g., glutathione, lipoic acid, N-acetyl

ysteineysteine NADPH and NADHNADPH and NADH Ubiquinone (coenzyme Q10)Ubiquinone (coenzyme Q10) Uric acidUric acid Enzymes:Enzymes:- copper/zinc and manganese-dependent - copper/zinc and manganese-dependent

superoxide dismutasesuperoxide dismutase- iron-dependent catalase- iron-dependent catalase- selenium-dependent glutathione peroxidase- selenium-dependent glutathione peroxidase

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b. Dietary Antioxidants Vitamin C Vitamin E Beta carotene and other carotenoids and oxycarotenoids, e.g., lycopene and lutein Polyphenols, e.g., flavonoids, flavones, flavonol’s, and Proanthocyanidinsc. Metal Binding Proteins Albumin (copper) Ceruloplasmin (copper) Metallothionein (copper) Ferritin (iron) Myoglobin (iron) Transferrin (iron)

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Defence mechanisms against free radical-induced Defence mechanisms against free radical-induced oxidative damage include the following:oxidative damage include the following:i.i.catalytic removal of free radicals and reactive catalytic removal of free radicals and reactive species by factors such as CAT, SOD, GPx and species by factors such as CAT, SOD, GPx and thiol-specific antioxidants;thiol-specific antioxidants;

ii. ii. binding of proteins (e.g., transferrin, binding of proteins (e.g., transferrin, metallothionein, haptoglobins, caeroplasmin) tometallothionein, haptoglobins, caeroplasmin) topro-oxidant metal ions, such as iron and copper;pro-oxidant metal ions, such as iron and copper;

iii. iii. protection against macromolecular damage by protection against macromolecular damage by proteins such as stress or heat shock proteins; proteins such as stress or heat shock proteins;

iviv. reduction of free radicals by electron donors, . reduction of free radicals by electron donors, such as GSH, vitamin E (such as GSH, vitamin E (α- α- tocopherol), vitamin C tocopherol), vitamin C (ascorbic acid), bilirubin, and uric acid(ascorbic acid), bilirubin, and uric acid

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