This include superoxide dismutase (SOD) and related model system

1. ROLE OF METAL BASED ANTI-OXIDANTS IN OUR BODY,
ESPECIALLY SUPEROXIDE DISMUTASE AND RELATED
SYSTEM
Presented by Churchil Sharma

2. INTRODUCTION
 Free radicals generated by our body by various endogenous mechanism.
The balance between free radicals and antioxidants is necessary for proper
physiological function.
If free radicals exceeds the body’s ability to regulate them results in oxidative
stress.
Antioxidant protects against oxidative stress by an interacting network of
antioxidant enzymes.
Free radicals include any species capable of independent existence that contain
one or more unpaired electron.

3. REACTIVE OXIDATIVE SPECIES
Radicals are involved in extracting electron to complete their own orbitals.
Includes HO•, HOO•, ROO• , etc.
O2 is 4 electron oxidizing agent and the product of this reaction is H2O
• O2+ e →O2
- ( by NADPH oxidase)
• O2
-+ 2 H++ e→ H2O2 (by superoxide dismutase)
• H2O2+ H++ e→ H2O+ HO• (by Fenton reaction)
• HO•+ H++ e→ H2O (by glutathione)
O2 O2
- H2O2
OH - H2O

4.  Fenton reaction: set of steps using iron that converts H2O2 to OH-
Fe 2+ + H2O2 → Fe3+ + OH- + HO•
Fe 3+ + H2O2 → Fe2+ + . OOH + H+
 The reactive species can also be generated by the myeloperoxidase enzyme in
the neutrophil cytoplasmic granules.
 Transitions metals don’t behave as free radicals but able to transport electron and
consequently to generate free radicals.
GENERATION OF ROS

5. DAMAGING ROLE OF ROS : OXIDATIVE STRESS
 Oxidative stress is the imbalance between the production of free radicals & ability
to detoxify their harmful effects through neutralisation by antioxidant.
Leads to oxidative damage to proteins, DNA & lipids which could lead to
cytotoxicity, genotoxicity and even carcinogenesis when damaging cells are
proliferate.
Occurs naturally within body & detoxified by antioxidants defence system in our
body but it is not efficient in removing all oxidative species, thus certain external
antioxidants are required.

6. DEFENCE SYSTEM OF ANTIOXIDANT & ITS MECHANISM
important in defending against free radicals.
have extra electron and can supply electron to neutralise free radicals
Antioxidants exert their effects via several basic mechanisms, which include:
1.) scavenging the species that initiate peroxidation
2.) quenching singlet oxygen,
3.)chelating metals,
4.)breaking free radical chain reactions, and
5.)reducing the concentration of O2

7. Antioxidant
natural
enzymatic
primary secondary
nonenzymatic
minerals vitamins carotenoids polyphenols
other
antioxidant
protein
non -
proteins
synthetic
CLASSIFICATION OF ANTIOXIDANTS:

8. ENZYMATIC ANTIOXIDANTS AND THEIR RELATED ACTIVITIES
Enzymatic
antioxidant Cellular location Substrate Reaction
Mn/Cu/Zn SOD Mitocondrial matrix
(Mn SOD) cytosol
(Cu/Zn SOD)
O2˙− O2˙− → H2O2
CAT Peroxisomes cytosol H2O2 2H2O2 → O2 + H2O
GSHPx Cytosol H2O2 H2O2 + GSH →
GSSG + H2O
Prx–I Cytosol H2O2 H2O2 + TrxS2 →
Trx(SH)2 + H2O

9. NON ENZYMATIC OXIDANT SCAVENGERS:
Minerals such as Cu, Zn, Mn, Fe ,Mg ,Se acts as cofactor and perform protective roles.
Vitamins such as Ascorbic acid or vitamin C & Alpha –Tocopherol.
Glutathione has antioxidant properties since thiol group in cystine moiety is a reducing
agent.

10. SUPEROXIDE DISMUTASE:
Metalloenzyme catalyses the disproportion reaction of superoxide in to water and
peroxide.
The spontaneous disproportionation of O2
- is bimolecular whereas the rates of the
enzyme-catalysed reaction are first-order.
2O2
-+2H+→O2+H2O2
Mechanism:
• Mn++ O2
−→ M(n-1)++O2
• M(n-1)++ O2
−→ Mn+(O2
2-)→ Mn++H2O2

11. STRUCTURE OF SOD
TYPE OF SOD METAL CENTRE
INVOLVED
Found
SOD1 Cu& Zn Prokaryotic cytoplasm
SOD2 Fe or Mn Mitochondria
SOD3 Ni Extracellular

12. SOD MODEL SYSTEM CATALYTIC CYCLE

13. REFERENCES:
• Rao, A. L.; Bharani, M.; Pallavi, V. Role of antioxidants and free radicals in
health and disease. Adv Pharmacol Toxicol 2006, 7, 29-38.
• Sheng, Y.; Abreu, I. A.; Cabelli, D. E.; Maroney, M. J.; Miller, A. F.;
Teixeira, M.; Valentine, J. S. Superoxide Dismutases and Superoxide
Reductases 2014,114, 3854-3918.
• Cristiana, F.; Elena, E.; Nina, Z. Superoxide Dismutase: therapeutic
targets in SOD related pathology 2014, 6, 975-988.

14. THANK YOU