Superoxide Dismutase

Superoxide Dismutase (SOD)
Comprehensive Notes for CSIR-NET, GATE, SLET, JAM

Introduction & Discovery

Superoxide Dismutase (SOD) is a crucial antioxidant enzyme that protects living cells from damaging superoxide radicals (O₂*) by converting them into less harmful oxygen (O₂) and hydrogen peroxide (H₂O₂), with different isoforms (Cu/Zn-SOD, Mn-SOD, Fe-SOD, EC-SOD) localized in various cell compartments (cytosol, mitochondria, extracellular space) and relying on metal cofactors like copper, zinc, iron, or manganese.

• Superoxide dismutase (SOD, EC 1.15.1.1) is a metalloenzyme that catalyzes the dismutation of superoxide radical (O₂⁻).
• Reaction: 2O₂⁻ + 2H⁺ → O₂ + H₂O₂
• Discovered in 1969 by McCord and Fridovich while studying erythrocuprein.
• First and most important antioxidant enzyme identified in aerobic organisms.
• Acts as first-line defense against reactive oxygen species (ROS).

Types and Isoforms of SOD

Type	Metal Cofactor	Location (Humans/Eukaryotes)	Structure	Distribution
Cu/Zn-SOD (SOD1)	Cu (catalytic) + Zn (structural)	Cytosol, nucleus, mitochondrial IMS	Dimer	Most eukaryotes
Mn-SOD (SOD2)	Mn	Mitochondria	Tetramer	Eukaryotic mitochondria, many bacteria
Extracellular SOD (SOD3)	Cu + Zn	Extracellular space	Tetramer	Mammals (extracellular)
Fe-SOD	Fe	Chloroplasts (plants), prokaryotes	Dimer/Tetramer	Prokaryotes, plant chloroplasts
Ni-SOD	Ni	Some bacteria (e.g., Streptomyces)	Hexamer	Rare, prokaryotic

Plants: Contain Fe-SOD (chloroplast), Mn-SOD (mitochondria/peroxisomes), Cu/Zn-SOD (cytosol, chloroplast, peroxisomes).

Structure

• Cu/Zn-SOD: Greek key β-barrel fold, highly conserved, electrostatic guidance channel.
• Mn/Fe-SOD: α-helical fold, homologous to each other but distinct from Cu/Zn-SOD.
• Active site metal cycles between two oxidation states.

Catalytic Mechanism

• Ping-pong (half-reaction) mechanism.
• Step 1: M⁽ⁿ⁺¹⁾⁺ + O₂⁻ → Mⁿ⁺ + O₂
• Step 2: Mⁿ⁺ + O₂⁻ + 2H⁺ → M⁽ⁿ⁺¹⁾⁺ + H₂O₂
• Rate is diffusion-limited (~10⁹ M⁻¹s⁻¹) – one of the fastest enzymes.

Biological Significance

• Primary defense against superoxide generated in respiration, photosynthesis, and stress.
• H₂O₂ produced is detoxified by catalase and peroxidases.
• In plants: Crucial for tolerance to drought, salinity, heavy metals, chilling, ozone.
• Also acts in ROS signaling (apoptosis, immune response).

Role in Diseases

High-weightage topic in exams:

• ALS (Amyotrophic Lateral Sclerosis): ~20% familial ALS caused by SOD1 mutations (gain-of-toxic function).
• Down syndrome: Trisomy 21 → overexpression of SOD1 → oxidative imbalance.
• Cancer, diabetes, Parkinson’s, Alzheimer’s, cardiovascular diseases.
• SOD mimetics (e.g., tempol, EUK-8, EUK-134) under research as therapeutics.

Inhibitors & Assay

• Cyanide: Inhibits Cu/Zn-SOD (does not inhibit Mn-SOD).
• Azide & H₂O₂: Inhibit Cu/Zn-SOD.
• Assay: Xanthine–xanthine oxidase system + NBT or cytochrome c reduction (indirect).

Exam-Oriented Key Points

• First antioxidant enzyme discovered (1969).
• Reaction: 2O₂⁻ + 2H⁺ → H₂O₂ + O₂
• SOD1 → Cytosolic, Cu/Zn; SOD2 → Mitochondrial, Mn; SOD3 → Extracellular, Cu/Zn.
• Mutation in SOD1 → Familial ALS.
• Rate near diffusion limit.
• Cyanide inhibits only Cu/Zn-SOD.
• No Nobel Prize for its discovery (often asked in trivia).

Test Your Knowledge on SOD

1. Who discovered superoxide dismutase?

A. Watson and Crick
B. McCord and Fridovich
C. Sanger and Pauling
D. Krebs and Calvin

Answer

B. McCord and Fridovich

2. Which isoform of SOD is located primarily in the mitochondria of eukaryotes?

A. SOD1 (Cu/Zn-SOD)
B. SOD2 (Mn-SOD)
C. SOD3 (ecSOD)
D. Fe-SOD

Answer

B. SOD2 (Mn-SOD)

3. The reaction catalyzed by SOD is:

A. O₂⁻ + H₂O₂ → O₂ + OH⁻
B. 2O₂⁻ + 2H⁺ → O₂ + H₂O₂
C. H₂O₂ → H₂O + ½O₂
D. 2H₂O₂ → 2H₂O + O₂

Answer

B. 2O₂⁻ + 2H⁺ → O₂ + H₂O₂

4. Mutations in which SOD gene are associated with familial Amyotrophic Lateral Sclerosis (ALS)?

A. SOD2
B. SOD1
C. SOD3
D. Fe-SOD

Answer

B. SOD1

5. Which inhibitor specifically inhibits Cu/Zn-SOD but not Mn-SOD?

A. Azide
B. Cyanide
C. Fluoride
D. Iodoacetate

Answer

B. Cyanide

6. The catalytic rate of SOD is approximately:

A. 10³ M⁻¹s⁻¹
B. 10⁶ M⁻¹s⁻¹
C. 10⁹ M⁻¹s⁻¹
D. 10¹² M⁻¹s⁻¹

Answer

C. 10⁹ M⁻¹s⁻¹

7. The following metal ions found in Superoxide Dismutase:

A. Zn(II) and Ni(II)
B. Zn(II) and Cu(II)
C. Cu(II) and Fe(II)
D. Cu(II) and Fe(III)

Answer

B. Zn(II) and Cu(II)

8. Which metal cofactors are characteristic of cytosolic and mitochondrial SOD isoforms respectively?

A. Fe for cytosol, Cu/Zn for mitochondria
B. Cu/Zn for cytosol, Mn for mitochondria
C. Mn for cytosol, Cu/Zn for mitochondria
D. Zn for both cytosol and mitochondria

Answer

B. Cu/Zn for cytosol, Mn for mitochondria

Use these notes and quiz for quick revision before CSIR-NET, GATE (Life Sciences/Biotechnology), JAM, SLET, and other competitive exams.