A 45-year-old with suspected lead poisoning has basophilic stippling on peripheral smear and urinary ALA elevated to 60 µg/dL. The mechanism by which lead inhibits haem synthesis is:
- A Inhibition of ALA synthase — reducing initial substrate formation
- B Inhibition of uroporphyrinogen decarboxylase — causing accumulation of uroporphyrinogen III
- C Inhibition of ALA dehydratase and ferrochelatase — blocking porphobilinogen formation and iron insertion ✓
- D Competitive inhibition of porphobilinogen deaminase — reducing haem B chain
Correct answer: C. Inhibition of ALA dehydratase and ferrochelatase — blocking porphobilinogen formation and iron insertion
Explanation
Lead primarily inhibits two enzymes: (1) ALA dehydratase (porphobilinogen synthase), causing ALA accumulation — the most sensitive indicator; and (2) ferrochelatase (haem synthase), blocking incorporation of iron into protoporphyrin IX. Result: elevated urinary ALA, elevated free erythrocyte protoporphyrin (FEP), and microcytic hypochromic anaemia. Basophilic stippling results from lead-induced inhibition of pyrimidine-5′-nucleotidase preventing ribosomal RNA degradation.
Reference: The Essentials of Forensic Medicine and Toxicology (Narayan Reddy), 34th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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