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SUPEROXIDE DISMUTASE
• Superoxide anion hydrogen peroxide + Dioxygen
• O2
- radicals are produced by respiration or photosynthesis
H2O and 2H+
OXIDATIVE
STRESS
Diabetes Mellitus Hypertension
Ischemic
Disease
Cancer
Neurodegenerative disease
Types of Superoxide Dismutase
Name of the enzyme type Action and presence Co-factor
present
• Cu-Zn superoxide
dismutase (SOD1)
Cu, Zn superoxide dismutase and
intermembrane space of the
mitochondria
Copper (Cu)
• manganese superoxide
dismutase (SOD2)
mitochondrial matrix Manganese (Mn)
• extracellular Cu-Zn
superoxide dismutase
(SOD3)
extracellular Cu, Zn superoxide
dismutase
Copper (Cu)
• Dimer of identical subunits (homodimer)
• Active sites face away from each other
• 151 amino acid residues in each subunit
• Copper ion acts as an electron transfer center in the active site
• Zinc ion serves as a structural scaffold and a contributes to the positive
charge of the active site attracting the O2-.
Cu 2+
Cu 1+
1. Superoxide binds to the
Cu2+SOD complex
2. electron from the superoxide is
transferred to reduced Cu2+, producing
Cu1+SOD and O2
3. Another
superoxide radical is
reduced by Cu1+ and
reacted with 2H+
giving H2O2
O2
-
O2
H2O2
2H+ and
O2
-
The redox potential of Mn-SOD with Mn3+/2+ lies between E°’ values of the
oxidation of superoxide to oxygen and the reduction of superoxide to
hydrogen peroxide.
Titania nanosheets : co-
immobilization
• Titania nanosheets – HRP and SOD
• Poly-diallyldimethylammonium chloride (PDADMAC) and poly-styrene
sulfonate (PSS)
• Polyelectrolyte-based sequential adsorption technique
electrostatic forces
polyelectrolytes
Carrier
1) Enzyme mimic : imitating the
function of natural enzymes
2) Manganese porphyrin SOD
mimics with a manganese metal
center surrounded by a porphyrin
ring.
3) Increased biodistribution
4) Alkyl chains were lengthened for
increased lipophilicity
5) Addition of oxygen to lengthy
alkyl chains for reduced toxicity
6) BuOE encapsulated in
mesoporous silica nanoparticles
7) Lipid-coated mesoporous silica
nanoparticles
Bacterial Sources : Caulobacter , Haemophilus, Pseudomonas, and
Escherichia coli
Eukaryotic sources : filamentous fungi and algae.
Recombinant biotechnology
Disadvantages
i. Deficient in metal co-factor
ii. In-vitro remetallization of the apoenzyme required
iii. Codon bias
iv. Glycosylation
SOD production from filamentous fungi :
Purified by fractional acetone precipitation followed by gel filtration
chromatography on a Sephadex G-75 column, ion-exchange chromatography
on DEAE (diethylaminoethyl) cellulose-52 and Mono Q columns, and
desalting on RP C18 column.
1. 50-L Fermentor was charged with 15L of beer waste yeast suspension and 15L of
nutrient solution.
2. Induction : 2% ethanol , air pressure increase (1 to 6 Bar) , H2O2
3. Aeration : 0.9 vvm at 28°C for 7h.
4. Centrifugation and Yeast cake is autolyse by addition of ethyl acetate
5. Purified chromatographically on carboxymethyl (CM) and lyophilized
6. SOD activity of 7.05×105 units
7. Specific activity of 8700 units/mg protein
• ion-exchange chromatography on Q-Sepharose, gel filtration on Superdex-75, and
immunoaffinity chromatography using anti-MnSOD antibody immobilized on
Sepharose
Suntory Ltd. (Japan) patented process
Current uses :
1) Cosmetic and manufacturing of other supplementary products to protect
from free radical damage
2) Prolong the survival period of organs for transplantation, laundry
ingredients to remove Amadori and Maillard products
3) Biosensors to detect superoxide anions (O2
-)
4) Bovine derived SOD commonly called as ORGOTEIN is available
commercially to treat inflammation and radiation induced side effects
Therapeutic Potentials Of Superoxide
Dismutase
i. May regulate cancer progression and can be used as a novel target
ii. Oxidative stress , proinflammatory response and apoptosis can be reduced in
CF cells
iii. Removal of O2
- and peroxynitrite (SOD mimetic) can help in the prevention of
cellular energetic failure & tissue damage related with ischemia and perfusion
iv. inhibitory agent of neutrophil-mediated inflammation
v. Neurodegenerative diseases
vi. Diabetes milletus
References
• Therapeutic potentials of superoxide dismutase
Review Article : H. Younus
• Industrial Production of Superoxide Dismutase (SOD): A Mini Review
Rajesh Kanna Gopal and Sanniyasi Elumalai
• Sarah L. Schlichte, Svetlana Romanova, and Matthew C. Zimmerman
Nanoformulation of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, prevents its acute hypotensive response
• Co-Immobilization of Superoxide Dismutase with Catalase on Soft Microparticles Formed by Self-Assembly of Amphiphilic
Poly(Aspartic Acid)
• Enas N.Danial Maha I. Alkhaaf
Co-immobilisation of superoxide dismutase and catalase using an in vitro encapsulation protocol
• James D. Crapo, Brian J. Day, and Irwin Fridovich.
Development of Manganic Porphyrin Mimetics of Superoxide Dismutase Activity
• Sarah L. Schlichte, Svetlana Romanova, [...], and Matthew C. Zimmerman
Nanoformulation of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, prevents its acute hypotensive response

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Superoxide dismutase

  • 2. • Superoxide anion hydrogen peroxide + Dioxygen • O2 - radicals are produced by respiration or photosynthesis H2O and 2H+ OXIDATIVE STRESS Diabetes Mellitus Hypertension Ischemic Disease Cancer Neurodegenerative disease
  • 3. Types of Superoxide Dismutase Name of the enzyme type Action and presence Co-factor present • Cu-Zn superoxide dismutase (SOD1) Cu, Zn superoxide dismutase and intermembrane space of the mitochondria Copper (Cu) • manganese superoxide dismutase (SOD2) mitochondrial matrix Manganese (Mn) • extracellular Cu-Zn superoxide dismutase (SOD3) extracellular Cu, Zn superoxide dismutase Copper (Cu) • Dimer of identical subunits (homodimer) • Active sites face away from each other • 151 amino acid residues in each subunit • Copper ion acts as an electron transfer center in the active site • Zinc ion serves as a structural scaffold and a contributes to the positive charge of the active site attracting the O2-.
  • 4. Cu 2+ Cu 1+ 1. Superoxide binds to the Cu2+SOD complex 2. electron from the superoxide is transferred to reduced Cu2+, producing Cu1+SOD and O2 3. Another superoxide radical is reduced by Cu1+ and reacted with 2H+ giving H2O2 O2 - O2 H2O2 2H+ and O2 -
  • 5. The redox potential of Mn-SOD with Mn3+/2+ lies between E°’ values of the oxidation of superoxide to oxygen and the reduction of superoxide to hydrogen peroxide.
  • 6.
  • 7. Titania nanosheets : co- immobilization • Titania nanosheets – HRP and SOD • Poly-diallyldimethylammonium chloride (PDADMAC) and poly-styrene sulfonate (PSS) • Polyelectrolyte-based sequential adsorption technique electrostatic forces polyelectrolytes Carrier
  • 8. 1) Enzyme mimic : imitating the function of natural enzymes 2) Manganese porphyrin SOD mimics with a manganese metal center surrounded by a porphyrin ring. 3) Increased biodistribution 4) Alkyl chains were lengthened for increased lipophilicity 5) Addition of oxygen to lengthy alkyl chains for reduced toxicity 6) BuOE encapsulated in mesoporous silica nanoparticles 7) Lipid-coated mesoporous silica nanoparticles
  • 9. Bacterial Sources : Caulobacter , Haemophilus, Pseudomonas, and Escherichia coli Eukaryotic sources : filamentous fungi and algae. Recombinant biotechnology Disadvantages i. Deficient in metal co-factor ii. In-vitro remetallization of the apoenzyme required iii. Codon bias iv. Glycosylation SOD production from filamentous fungi : Purified by fractional acetone precipitation followed by gel filtration chromatography on a Sephadex G-75 column, ion-exchange chromatography on DEAE (diethylaminoethyl) cellulose-52 and Mono Q columns, and desalting on RP C18 column.
  • 10. 1. 50-L Fermentor was charged with 15L of beer waste yeast suspension and 15L of nutrient solution. 2. Induction : 2% ethanol , air pressure increase (1 to 6 Bar) , H2O2 3. Aeration : 0.9 vvm at 28°C for 7h. 4. Centrifugation and Yeast cake is autolyse by addition of ethyl acetate 5. Purified chromatographically on carboxymethyl (CM) and lyophilized 6. SOD activity of 7.05×105 units 7. Specific activity of 8700 units/mg protein • ion-exchange chromatography on Q-Sepharose, gel filtration on Superdex-75, and immunoaffinity chromatography using anti-MnSOD antibody immobilized on Sepharose Suntory Ltd. (Japan) patented process
  • 11.
  • 12.
  • 13. Current uses : 1) Cosmetic and manufacturing of other supplementary products to protect from free radical damage 2) Prolong the survival period of organs for transplantation, laundry ingredients to remove Amadori and Maillard products 3) Biosensors to detect superoxide anions (O2 -) 4) Bovine derived SOD commonly called as ORGOTEIN is available commercially to treat inflammation and radiation induced side effects
  • 14. Therapeutic Potentials Of Superoxide Dismutase i. May regulate cancer progression and can be used as a novel target ii. Oxidative stress , proinflammatory response and apoptosis can be reduced in CF cells iii. Removal of O2 - and peroxynitrite (SOD mimetic) can help in the prevention of cellular energetic failure & tissue damage related with ischemia and perfusion iv. inhibitory agent of neutrophil-mediated inflammation v. Neurodegenerative diseases vi. Diabetes milletus
  • 15. References • Therapeutic potentials of superoxide dismutase Review Article : H. Younus • Industrial Production of Superoxide Dismutase (SOD): A Mini Review Rajesh Kanna Gopal and Sanniyasi Elumalai • Sarah L. Schlichte, Svetlana Romanova, and Matthew C. Zimmerman Nanoformulation of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, prevents its acute hypotensive response • Co-Immobilization of Superoxide Dismutase with Catalase on Soft Microparticles Formed by Self-Assembly of Amphiphilic Poly(Aspartic Acid) • Enas N.Danial Maha I. Alkhaaf Co-immobilisation of superoxide dismutase and catalase using an in vitro encapsulation protocol • James D. Crapo, Brian J. Day, and Irwin Fridovich. Development of Manganic Porphyrin Mimetics of Superoxide Dismutase Activity • Sarah L. Schlichte, Svetlana Romanova, [...], and Matthew C. Zimmerman Nanoformulation of the superoxide dismutase mimic, MnTnBuOE-2-PyP5+, prevents its acute hypotensive response