Which of the following is the biochemical basis for the pathogenic effect of diphtheria toxin on host cells?

Explanation

## Mechanism of Diphtheria Toxin Action ### Structure and Function of Diphtheria Toxin **Key Point:** Diphtheria toxin is a two-chain A–B exotoxin. The A (catalytic) chain catalyzes ADP-ribosylation of elongation factor 2 (EF-2), a critical ribosomal protein required for translocation during protein synthesis. ### Step-by-Step Mechanism 1. **Binding:** B chain binds to heparin-binding EGF-like growth factor (HB-EGF) receptor on host cell 2. **Internalization:** Receptor-mediated endocytosis 3. **Translocation:** Acidic endosomal pH triggers conformational change; A chain enters cytoplasm 4. **Catalytic Action:** A chain catalyzes ADP-ribosylation of diphthamide residue on EF-2 5. **Result:** EF-2 inactivation → inhibition of ribosomal translocation → **protein synthesis halts** ### Consequence of EF-2 Inactivation | Effect | Outcome | |--------|----------| | **Protein synthesis cessation** | Cell death within hours | | **Tissue necrosis** | Local pseudomembrane formation | | **Systemic toxicity** | Myocarditis, neuritis, renal failure | | **Lethal dose** | ~0.1 μg/kg body weight | **Mnemonic:** **ADP-Ribosylation of EF-2** — **ARE** toxins (diphtheria, Pseudomonas exotoxin A, *Vibrio cholerae* toxin all modify host proteins via ADP-ribosylation or similar mechanisms). **High-Yield:** This is the most frequently tested mechanism in NEET PG. The key detail is **ADP-ribosylation of EF-2**, not just "protein synthesis inhibition." ### Why Not the Other Options? - **Peptidoglycan synthesis:** Diphtheria toxin acts on host cells, not bacterial cells. It does not inhibit bacterial cell wall synthesis. - **Apoptosis via caspases:** While cell death occurs, it is due to protein synthesis cessation, not caspase-mediated apoptosis. - **Membrane pores:** Diphtheria toxin does not form ion channels or pores; it is a catalytic toxin, not a pore-forming toxin.