The document discusses antioxidants and their role in human health. It defines antioxidants as molecules that inhibit the oxidation of other molecules and prevent free radical damage. Free radicals are unstable molecules that can damage cells, but antioxidant enzymes work to stabilize free radicals. Many health conditions are linked to oxidative stress caused by free radicals, including aging, cancer, diabetes and neurodegenerative diseases. The body has both endogenous and dietary antioxidant systems to protect against free radical damage through catalytic removal of radicals and protection of macromolecules.

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Antioxidant
Enzymes and
Human Health
By
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 andAs a result of this, vital cellular structures and
functions are lost and resulting a pathologicalfunctions are lost and resulting a pathological
conditions.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.

8. • 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).

9. 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.

10. • 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

11. • Reactive Oxygen Species:-
Reactive oxygen species (ROS) is a term
that encompasses all highly reactive, oxygen
containing molecules, including free radicals
• Types of ROS include
the 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 byapproximately 90% of the oxygen utilized by
the cell is consumed by the mitochondrialthe cell is consumed by the mitochondrial
electron transport system.electron transport system.
• Oxidative burst from phagocytes (white bloodOxidative burst from phagocytes (white blood
cells) as part of the mechanism by whichcells) as part of the mechanism by which
bacteria and viruses are killed, and by whichbacteria and viruses are killed, and by which
foreign proteins (antigens) are denatured.foreign proteins (antigens) are denatured.
• Xenobiotic metabolism, i.e., detoxification ofXenobiotic 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:

15. 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 forms
ºOH, as given following reaction :

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Antioxidant protection system
To 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 ysteineThiols, e.g., glutathione, lipoic acid, N-acetyl ysteine
 NADPH and NADHNADPH and NADH
 Ubiquinone (coenzyme Q10)Ubiquinone (coenzyme Q10)
 Uric acidUric acid
 Enzymes:Enzymes:
- copper/zinc and manganese-dependent superoxide- copper/zinc and manganese-dependent superoxide
dismutasedismutase
- 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
Proanthocyanidins
c. Metal Binding Proteins
 Albumin (copper)
 Ceruloplasmin (copper)
 Metallothionein (copper)
 Ferritin (iron)
 Myoglobin (iron)
 Transferrin (iron)

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Defence mechanisms against free radical-inducedDefence mechanisms against free radical-induced
oxidative damage include the following:oxidative damage include the following:
i.i.catalytic removal of free radicals and reactivecatalytic removal of free radicals and reactive
species by factors such as CAT, SOD, GPx and thiol-species by factors such as CAT, SOD, GPx and thiol-
specific antioxidants;specific antioxidants;
ii.ii. binding of proteins (e.g., transferrin,binding of proteins (e.g., transferrin,
metallothionein, haptoglobins, caeroplasmin) tometallothionein, haptoglobins, caeroplasmin) to
pro-oxidant metal ions, such as iron and copper;pro-oxidant metal ions, such as iron and copper;
iii.iii. protection against macromolecular damage byprotection 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, such. reduction of free radicals by electron donors, such
as GSH, vitamin E (as GSH, vitamin E (α-α- tocopherol), vitamin C (ascorbictocopherol), vitamin C (ascorbic
acid), bilirubin, and uric acidacid), bilirubin, and uric acid

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