3. • There are two types of antioxidants:
exogenous and endogenous.
• Exogenous antioxidants are antioxidants we
get from our diet and endogenous
antioxidants are made by our bodies.
• Endogenous antioxidants repair free radical
damage on the inside by initiating cell
regeneration.
• Exogenous antioxidants repair some free
radical damage from the outside on in by
stimulating cell regeneration.
4.
5.
6. • Endogenous antioxidants, which are products
of the body’s metabolism categorized based on
their activity- enzymatic and non-enzymatic
antioxidants.
• Enzymatic antioxidants work by breaking
down and removing free radicals.
• The antioxidant enzymes convert dangerous
oxidative products to hydrogen peroxide (H2O2)
and then to water, in a multi-step process in
presence of cofactors such as copper, zinc,
manganese, and iron.
Endogenous Antioxidants
7. • Non-enzymatic antioxidants work by
interrupting free radical chain reactions.
• The non-enzymatic substances taking part in
the first line of defence belong to preventive
antioxidants and in blood plasma are
represented by ceruloplasmin, ferritin,
transferrin and albumin.
• These proteins inhibit the formation of new
reactive species by binding transition metal
ions (e.g. iron and copper).
8. ANTIOXIDANT DEFENCE
• The exposure of cells, tissues and the extracellular
matrix to the harmful effects of free radicals causes a
cascade of reactions and induces activation of multiple
internal defence mechanisms, which provide
elimination of free radicals and their derivatives.
• These mechanisms are: -
• preventive - being the first line of defence, preventing
reactions of free radicals and their derivatives with
biological substances in the body
• repairing - involving interruption into a radical oxidation
reaction,
• inactivating the products of free radical reaction and their derivatives-
by repairing or eliminating structural damage
9. first line defence antioxidants
[ENZYMATIC DEFENCE]
• These are a collection of antioxidants that act to
suppress or prevent the formation of free radicals or
reactive species in cells.
• They are very fast in neutralizing any molecule with the
potential of developing into a free radical or any free
radical with the ability to induce the production of other
radicals.
Superoxide dismutase (SOD)- catalyzes the
disproportionation reaction of superoxide anion to
hydrogen peroxide and molecular oxygen.
Catalase (CAT), Glutathione Peroxidase (GPx),
glutathione reductase (GR) and Peroxiredoxins (Prxs) -
neutralize hydrogen peroxide, yielding water (catalase
glutathione peroxidase) and oxygen molecule (catalase).
10. second line defence antioxidants
[NON ENZYMATIC DEFENCE]
• This group of antioxidants is often referred to as
scavenging antioxidants.
• They scavenge active radicals to inhibit chain initiation
and break chain propagation reactions.
• They neutralize or scavenge free radicals by donating
electron to them, and in the process become free
radicals themselves but of lesser damaging effects.
• These ‘new radicals’ are easily neutralized and made
completely harmless by other antioxidants in this group.
• Most antioxidants including ascorbic acid, uric
acid, glutathione, which are hydrophilic and alpha
tocopherol (vitamin E) and ubiquinol which are lipophilic
belong to this category.
11. Third line defense antioxidants
• This category of antioxidants only comes into play
after free radical damage has occurred.
• They are de novo enzymes which repair the damage
caused by free radicals to biomolecules and
reconstitute the damaged cell membrane.
• They are a group of enzymes for repair of
damaged DNA, protein and lipids.
• They also do a sort of ‘clean up duty’, they recognize,
breakdown and remove oxidized or damaged proteins,
DNA and lipids, to prevent their accumulation which
can be toxic to body tissues.
• Common examples include The DNA repair
enzyme systems (polymerases, glycosylases and
nucleases), proteolytic enzymes (proteinases,
proteases and peptidases) which are located both in
cytosol and mitochondria of mammalian cells.
12. Fourth line defense antioxidants
• The action of these ‘antioxidants’ basically
involves an adaptation mechanism in which they
utilize the signals required for free radicals
production and reaction to prevent the
formation or reaction of such free radicals.
• The signal generated from the free radical
formed induces the formation and transport of
an appropriate antioxidant to the right site.
15. Superoxide dismutase
• Superoxide dismutase (SOD) is the first detoxification
enzyme and most powerful antioxidant in the cell.
• It is an important endogenous antioxidant enzyme that
acts as a component of first line defense system
against reactive oxygen species (ROS).
• It catalyzes the dismutation of two molecules of
superoxide anion (∗O2) to hydrogen peroxide (H2O2)
and molecular oxygen (O2), consequently rendering
the potentially harmful superoxide anion less
hazardous.
16. • SOD is a metalloenzyme and hence, requires a metal
cofactor for its activity.
• On the basis of the type of metal ion required as
cofactor by SOD, various forms of the enzyme exist.
• The metal ions which are normally bound by SOD are
iron (Fe), zinc (Zn) copper (Cu) and manganese (Mn).
• In this regards, SODs are classified into three forms :
(i) Fe-SOD which is commonly found in prokaryotes and
chloroplasts of some plants
(ii) Mn-SOD which is present in prokaryotes and
mitochondria of eukaryotes and
(iii) Cu/Zn-SOD is predominant in eukaryotes and more
distributed, localized basically in cytosol but also found
in chloroplasts and peroxisomes
17. • SOD is used in cosmetics and personal care
products as an anti-aging ingredient and
antioxidant due to its ability to reduce free radical
damage to the skin, therefore preventing
wrinkles, fine lines, and age spots, and it also
helps with wound healing, softens scar tissue,
protects against UV rays, and reduces other signs
of aging.
• SOD is used therapeutically in
CANCER,DIABETES,ISCHEMIA,
NEURODEGENERATIVE DISORDERS, CYSTIC
FIBROSIS, INFLAMMATORY DISORDERS
USES -SOD
18. CATALASE
• Catalase (CAT) is a 240 kilodalton (kDa) tetrameric
protein with four similar subunits.
• Each polypeptide subunit is 60 kDa in weight and
contains a single ferriprotoporphyrin.
• CAT is a common antioxidant enzyme present almost
in all living tissues that utilize oxygen.
• The enzyme uses either iron or manganese as a
cofactor and catalyzes the degradation or reduction of
hydrogen peroxide (H2O2) to water and molecular
oxygen, consequently completing the detoxification
process imitated by SOD.
19. • CAT is highly efficient- it can breaks down millions of
hydrogen peroxide molecules in one second.
• The activity of CAT takes place in two steps.
A molecule of hydrogen peroxide oxidizes the heme to
an oxyferryl species.A porphyrin cation radical is
generated when one oxidation equivalent is removed
from iron and one from the porphyrin ring.
A second hydrogen peroxide molecule acts as a reducing
agent to regenerate the resting state enzyme, producing
a molecule of oxygen and water.
Enzyme[porphyrin Fe(III)] + H2O2 Enzyme
[porphyrin Fe(IV)-O] + H2O (compound)
Enzyme[porphyrin Fe(IV)-O] + H2O2 Enzyme
[porphyrin Fe(III)] + H2O + O2 (free enzyme)
20. Uses-Catalase
Cancer therapy
Catalase assists to regulate production of
cytokines, protect oxidative injury, and repress
replication of SARS-CoV-2
Diabetes, Alzheimer’s disease, Parkinson’s
disease
21. Glutathione Peroxidases
• Glutathione Peroxidase (GPx) is an
important intracellular enzyme that
breakdown hydrogen peroxides (H2O2) to
water and lipid peroxides to their
corresponding alcohols mainly in the
mitochondria and sometimes in the cytosol.
22. • Most times, its activity depends on a micronutrient
cofactor known as selenium. For this reason, GPX is
often referred to as a selenocysteine peroxidase.
• The enzyme plays a more crucial role of inhibiting lipid
peroxidation process, and therefore protects cells
from oxidative stress.
• According to Morón and Cortázar, there are at least
eight GPx enzymes in human, GPx1–GPx8.
• GPx-1 is a crucial antioxidant enzyme involved in
preventing the harmful accumulation of intracellular
hydrogen peroxide.
• It is present in all cells, found in cytosolic,
mitochondrial, and, in some cells, in peroxisomal
compartments.
23.
24. USES-GPx
• Combination of certain antioxidants like
glutathione, vitamin C and E, selenium and
glutathione peroxidase are very powerful in
helping the body fight against the free
radicals.
• GSH ensures that the red blood cells remain
intact and protect the white blood cells (which
are responsible for immunity).
25. Glutathione
(Non enzymatic endogenous antioxidant)
• Glutathione is a tripeptide which is composed of
cysteine, glutamic acid, and glycine.
• GSH has two structural characteristic: γ-glutamyl
linkage and sulfhydryl (-SH) group.
• GSH is known for its multiple physiological functions as
an antioxidant against ROS and free radicals in
detoxification of xenobiotic compounds
• Glutathione, in thiol reduced form (GSH), turns itself
into disulfide oxidized form (GSSG) with creating
disulfide bridge with another glutathione molecule
while playing role in detoxification of these molecules
by reacting with hydrogen peroxides or lipid peroxides,
with the reaction catalyzed by the GPx enzyme.
26. • The endogenously produced hydrogen peroxide is
reduced by GSH in the presence of selenium-
dependent GSH peroxidase.
• As a result, GSH is oxidized to GSSG, which in turn is
reduced back to GSH by GSSG reductase at the
expense of NADPH, forming a redox cycle.
• Organic peroxides can be reduced by either GSH
peroxidase or GSH S-transferase.
• Severe oxidative stress may overcome the ability of
the cell to reduce GSSG to GSH, leading to
accumulation of GSSG within the cytosol.
• To protect the cell from a shift in the redox
equilibrium, GSSG can be actively exported out of the
cell or react with a protein sulfhydryl (PSH) group,
leading to the formation of a mixed disulfide(PSSG).
• Thus, severe oxidative stress depletes cellular GSH
27.
28. GSH serves several vital functions,
1)detoxifying electrophiles
2) maintaining the essential thiol status of
proteins by preventing oxidation of -SH groups
or by reducing disulfide bonds induced by
oxidant stress
3) scavenging free radicals
4)providing a reservoir for cysteine
5) modulating critical cellular processes such as
DNA synthesis,microtubular-related
processes, and immune function
29. Uses-Glutathione
• Reduces cell damage in alcoholic and non
alcoholic fatty liver disease
• Improves insulin resistance in older individuals
• Increases mobility for people with peripheral
artery disease