2. • The oxygen is needed for each living organism
for survival .but oxygen is toxic as well.
According to Salvemini oxygen is double edge
sword :it is vital for life but leads to formation
of toxic by products such as superoxide (o-
2)
anion. oxygen more prone to produce
superoxide radicals because molecular oxygen
contain two unpaired electrons with parallel
spins
Free radicals

3. • These unpaired electrons reside in separate
orbitals unless their spins are opposed.
Reduction of o2 by direct insertion of a pair of
electrons,e-
,into its partially filled orbitals is
not possible without inversion of one
electronic spin and such inversion of spin is a
slow process

4. hence electrons are added molecular oxygen as
single electron molecule when oxygen
molecule takes up one electron,by univalent
reduction,it becomes ”superoxide” anion O-2.
O2 + e-
O2
‑

5. Ionizing radiation (x-rays and UV) can lyse
water, leading to the formation of hydroxyl
radicals. Transition metal ions, including Cu+
,
Co2+
, Ni2+
and Fe2+
can react nonenzymically with
oxygen or hydrogen peroxide, again leading to
the formation of hydroxyl radicals.
There Are Multiple Sources of Oxygen
radicals in the Body

6. Peroxidation (auto-oxidation) of lipid exposed to
oxygen is responsible not only for deterioration of
foods (rancidity), but also for damage to tissues in
vivo, where it may be a cause of cancer,
inflammatory diseases, atherosclerosis, and aging.
The deleterious effects ae considered to be caused
by free radicals (ROO*
, RO*
, OH*
) produced
LIPID PEROXIDATION IS A
SOURCE OF FREE RADICALS

7. During peroxide formation from fatty acid
containing methylene-interrupted double
bonds, that is, those found in the naturally
occurring polyunsaturated fatty acids. Lipid
peroxidation is a chain reaction providing a
continuous supply of free radicals that initiate
future peroxidation and thus has potentially
devastating effects. The whole process can be
depicted as follows:

8. 1. Initiation:
ROOH + Metal(n)+
→ ROO*
+ Metal(n-1)+
+ H+
X*
+ RH→ R*
+ XH
2. Propagation:
R*
+ O2 → ROO*
ROO*
+ RH → ROOH + R*,
etc
3. Termination:
ROO*
+ ROO*
→ ROOR + O2
ROO*
+ R*
→ ROOR
R*
+ R*
→ RR

9. Free radicals are highly reactive molecular
species with an unpaired electron; they persist
for only a very short time (of the order of 10-9
to 10-12
sec) before they collide with another
molecule and either abstract or donate an
electron in order to achieve stability.
Free Radical Reactions Are Self-
Perpetuating Chain Reactions

10. Free radicals are formed in the body under
normal conditions. They cause damage to
nucleic acids, proteins, and lipids in cell
membranes and plasma lipoproteins. This can
cause cancer, atherosclerosis and coronary
artery disease, and autoimmune diseases.
BIOMEDICAL IMPORTANCE

12. • Interaction between antioxidants in the lipid phase
(cell membranes) and the aqueous phase (cytosol).
• (R•, free radical; PUFA-OO•, peroxyl radical of
polyunsaturated fatty acid in membrane phospholipid;
PUFA-OOH, hydroxyperoxy polyunsaturated fatty acid
in membrane phospholipid, released into the cytosol as
hydroxyperoxy polyunsaturated fatty acid by the action
of phospholipase A2; PUFA-OH, hydroxy
polyunsaturated fatty acid; Toc-OH vitamin E [
-tocopherol]; TocO•, tocopheroxyl radical; Se, selenium;
GSH,

13. • reduced glutathione; GS-SG, oxidized
glutathione, which is reduced to GSH after
reaction with NADPH, catalyzed by glutathione
reductase; PUFA-H, polyunsaturated fatty acid.)

14. • Antioxidant and Pro-Oxidant Roles of Vitamin C
• Antioxidant roles:
• Ascorbate + O2
–
H2O2 + monodehydroascorbate;
catalaseand peroxidases catalyze the reaction: 2H2O2
2H2O + O2Ascorbate + OH H2O + monodehydroascorbate

15. • Pro-oxidant roles:
– Ascorbate + O2 O2– + monodehydroascorbate
Ascorbate + Cu2+ Cu++
monodehydroasacorbate
Cu+
+ H2O2 Cu2+
+ OH–
+ OH

16. In so doing, they generate a new radical from the
molecule with which they collided. The most
damaging radicals in biological systems are
oxygen radicals especially superoxide, O2 -,
hydroxyl, OH., and perhydroxyl, O2H., Tissue
damage caused by oxygen radicals in often called
oxidative damage, and factors that protect against
oxygen radical damage are known as
antioxidants.

17. • superoxide dismutase:this enzyme is present In
both cytosol and mitochondria.It can destroy
superoxide anionsO-
2
• 2H+
+2O-
2
superoxidedismutase
H2O2+O2
Scavengers of free radicals

18. • The enzyme is present in all major aerobic
tissues protecting aerobic organisms against
the potential toxic effects of superoxide anion
O-
2 .

19. • Catalase
• This enzyme having high Km value situated
close to aerobic dehydrogenases , like liver
peroxisomes, can destroy H2o2 formed in the
tissues to O2.
• H2o2+H2O2 CATALASE 2H2O+O2

20. • Glutathuone Peroxidase:
• When H2O2 level is less than optimum requird
forhydrogenperoxidatio by catalase,the selenium
containing enzyme Glutathione peroxidase can
destroyH2O2with reduced gluthion(G-SH),having low
Km,present in cytosole and mitochondria
• H2O2+2G-SH G-S-S-G + 2H2O
• Reduced glutathione oxidized glutathione