free radicals and antioxidant system.ppt

1. FREE RADICALS AND
ANTIOXIDANT SYSTEM

2. FREE RADICALS
 A molecule or a
molecular species that
contain one or more
unpaired electrons ,
and is capable of
independent existence

3. characterisitcs
 Highly reactive
 Very short half life
 Can generate new radicals by chain
reaction
 Cause damage to biomolecules, cells
and tissues

4. ROS (reactive oxygen species)
Free radicals
superoxide, O2
· -
hydroxyl radical, OH ·
peroxyl, ROO ·
alkoxyl, RO ·
hydroperoxyl, HO2
·
Particals, which are not
free radicals
hydrogen peroxide, H2O2
(Fenton´s reaction)
hypochlorous acid, HClO
ozone, O3
singlet oxygen, 1O2

5. RNS (reactive nitrogen
species)
Free radicals
nitrogen(II) oxide, NO .
nitrogen(IV) oxide, NO2
.
Particals, which are not free
radicals
nitrosyl, NO+
nitrous acid, HONO
nitogen(III) oxide, N2O3
peroxynitrite, ONOO -
alkylperoxinitrite, ROONO

6. Sources
 Cellular metabolism
 Leakage of electron transport chain
 Production of H2O2 and O2ˉ by oxidase
enzyme
 Due to chain reaction of membrane lipid
peroxidation
 Peroxisomal generation of O2 and H2O2
 During the synthesis of prostaglandins

7.  Production of nitric oxide from arginine
 During the course of phagocytosis
 In the oxidation of heme to bile pigments
 As a result of auto-oxidation

8.  Environmental effects
 As a result of drug metabolism
 Due to damages caused by ionized
radiations on tissues
 Photolysis of O2 by light
 Photoexcitation of organic molecules
 Cigarette smoke contains free radicals, and
trace metals that generate OHˉ
 Alcohol, promoting lipid peroxidation

9. Benificial effect of free radicals

10. Harmful effect of free radicals
 Free radicals beget free radicals
 Proteins
 cause oxidation of sulfhydryl groups, and
modification of certain aminoacids
 may damage proteins by fragmentation,
cross-linking and aggregation
 loss of biological activity of proteins

11.  Lipids
 Induces peroxidation of membrane lipids
on three stages
 Initiation phase
 Propagation phase
 Termination phase
 Malondialdehyde (MDA) is a marker

12.  Carbohydrates
 Oxidation of monosaccharides can produce
H2O2 and oxoaldehydes
 linkage of carbohydrates to proteins
increases the susceptibility of proteins to
the attack by free radicals

13.  Nucleic acids
 may cause DNA strand breaks,
fragmentation of bases and deoxyribose

14. Antioxidant
O-
2, 1O2, .OH, H2O2,
Cu, Fe. R•, RO•, ROO •
R•, RO•,
ROO•,
1O2, O-
2,
-OH, H2O2,
Cu, Fe
Prooxidant Jail
Are you ready to fight the attack of prooxidants?

15. Antioxidants in biological
system
 A substance that significantly delays or
inhibits oxidation of a substrate

17. Classification of antioxidants
 Antioxidants in relation to lipid
peroxidation
 Preventive antioxidants
 Catalase,
 Glutathione peroxidase
 Chain breaking antioxidants
 Superoxide dismutase
 Vitamin E
 Uric acid

18. 2O2·- H2O2 O2 + H2O
2GSH GSSG + 2H2O
NADP+
NADPH + H+
Superoxide dismutase
2H+
Catalase
Glutathione Oxidase
Glutathione Reductase
NADP+ Reductase
Superoxide dismutase

19. Functions of GSH-dependent
Enzymes
L-OH
H2O GSSG NADPH
L-OOH
H2O2
GSH NADP+
X.
GSX
X-Mercapturic Acid
GSH Px
GSH-TR
GSH--Rx

20.  Antioxidants according to their location
 Plasma antioxidants
 β-carotene, Ascorbic acid
 Bilirubin, uric acid, ceruloplasmin, transferrin
 Cell membrane antioxidants
 α-tocopherol
 Intracellular antioxidants
 superoxide dismutase
 Catalase
 Glutathione peroxidase

21.  Antioxidants according to their nature
and action
 Enzymatic antioxidants
 Superoxide dismutase, catalase
 Non-enzymatic antioxidants
 Nutrients
 Caratenoids, ascorbic acid, α-tocopherols
 Metabolic
 Ceruloplasmin, albumin, bilirubin,transferrin, ferritin,
uric acid