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
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
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.