Antioxidant Enzymes

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Antioxidant Enzymes: Basics - Oxidative Stress Busters

  • Oxidative stress: Imbalance between pro-oxidants (ROS/RNS) and antioxidant defenses.
  • Reactive Oxygen Species (ROS): Highly reactive molecules, e.g., superoxide radical ($O_2^{\cdot-}$), hydroxyl radical ($\cdot OH$), hydrogen peroxide ($H_2O_2$).
  • Cellular damage: ROS attack lipids (peroxidation), proteins (denaturation), and DNA (mutations).
  • Antioxidant enzymes: Endogenous defense system; neutralize ROS to protect cellular integrity.
    • Key examples: Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx). Oxidative Stress, ROS, and Antioxidant Defense

⭐ The primary defense against superoxide radicals ($O_2^{\cdot-}$) is Superoxide Dismutase (SOD), converting them to $H_2O_2$ and $O_2$.

Antioxidant Enzymes: SOD - Superoxide Slayer

  • Full Name: Superoxide Dismutase.
  • Core Function: Neutralizes highly reactive superoxide radicals ($O_2^{\cdot-}$), preventing oxidative damage.
  • Reaction: $2O_2^{\cdot-} + 2H^+ \rightarrow H_2O_2 + O_2$.
  • Key Isoenzymes & Locations:
    • SOD1 (Cu/Zn-SOD): Cytosol. 📌 Cu/Zn in Cytosol.
    • SOD2 (Mn-SOD): Mitochondrial matrix. 📌 Mn in Mitochondria.
    • SOD3 (EC-SOD): Extracellular space.
  • Significance: Critical first-line enzymatic defense against $O_2^{\cdot-}$ toxicity. SOD isoenzymes and superoxide dismutation reaction

⭐ Mutations in the gene for SOD1 (Cu/Zn-SOD) are associated with familial Amyotrophic Lateral Sclerosis (fALS).

Antioxidant Enzymes: Catalase - Peroxide Pacifier

  • Function: Neutralizes hydrogen peroxide ($H_2O_2$) into water and oxygen.
    • Reaction: $2 H_2O_2 \rightarrow 2 H_2O + O_2$
  • Location: Predominantly in peroxisomes; also cytoplasm, mitochondria.
  • Structure: Tetrameric; each subunit contains a heme (iron protoporphyrin IX) prosthetic group.
  • High turnover number: Extremely efficient in detoxification.
  • Clinical Significance:
    • Acatalesemia (Takatsuki disease): Rare genetic deficiency; leads to ↑ risk of oral ulcerations, progressive gangrene.
    • Protects cells from oxidative damage by $H_2O_2$. Mn-catalase crystal, hexameric assembly, and active site

⭐ Catalase has one of the highest turnover numbers of all enzymes, decomposing millions of $H_2O_2$ molecules per second per active site at its optimum pH (around 7.0).

Antioxidant Enzymes: Glutathione System - Detox Dynamo Duo

Critical enzymatic defense neutralizing $H_2O_2$ and lipid peroxides (ROOH), protecting cells from oxidative damage.

  • Glutathione (GSH):
    • Tripeptide ($\gamma$-Glu-Cys-Gly); major water-soluble antioxidant and cellular reductant.
    • Cysteine's sulfhydryl (-SH) group donates reducing equivalents.
  • Glutathione Peroxidase (GPx):
    • Selenium-dependent enzyme (contains selenocysteine).
    • Catalyzes: $2GSH + H_2O_2 \rightarrow GSSG + 2H_2O$; also reduces organic peroxides (ROOH to ROH).
    • Forms oxidized Glutathione Disulfide (GSSG).
  • Glutathione Reductase (GR):
    • FAD-dependent flavoenzyme (FAD from Vit B2 - Riboflavin).
    • Regenerates active GSH from GSSG: $GSSG + NADPH + H^+ \rightarrow 2GSH + NADP^+$.
    • Requires NADPH, mainly from Hexose Monophosphate (HMP) Shunt.

Glutathione antioxidant pathway diagram

⭐ G6PD deficiency causes ↓NADPH, impairing GR's GSH regeneration. This increases RBC susceptibility to oxidative hemolysis, especially with oxidant drugs like primaquine. (📌 G6PD for GSH)

  • SOD1 mutations: Linked to Amyotrophic Lateral Sclerosis (ALS).
  • Catalase deficiency (Acatalasemia): Rare; may cause oral ulcers (Takahara's disease).
  • GPx dysfunction: Selenium deficiency impairs activity; linked to Keshan disease (cardiomyopathy).
  • GR dysfunction: Riboflavin (B2) deficiency reduces activity; impacts glutathione recycling.
  • G6PD deficiency: ↓NADPH → ↓reduced glutathione → hemolytic anemia on oxidant exposure.

⭐ G6PD deficiency is the most common human enzyme defect, predisposing to drug-induced hemolytic anemia.

High‑Yield Points - ⚡ Biggest Takeaways

  • Superoxide Dismutase (SOD): Mn-SOD (mitochondrial) & Cu/Zn-SOD (cytosolic) convert superoxide (O₂⁻) to H₂O₂.
  • Catalase: Peroxisomal enzyme; degrades H₂O₂ to H₂O + O₂. High in liver, erythrocytes.
  • Glutathione Peroxidase (GPx): Selenium-dependent; reduces H₂O₂ and lipid peroxides using GSH.
  • Glutathione Reductase (GR): Regenerates GSH from GSSG using NADPH (from HMP shunt).
  • Deficiencies in these enzymes ↑ oxidative stress, leading to cellular damage and disease.

Practice Questions: Antioxidant Enzymes

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Which of the following disorders presents with repeated catalase positive infections?

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Flashcards: Antioxidant Enzymes

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Ferroptosis is triggered when there are low levels of _____.

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Ferroptosis is triggered when there are low levels of _____.

reduced glutathione

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