A 4-year-old child living in an old house with peeling paint is found to have hemoglobin 8.5 g/dL, MCV 70 fL, and prominent basophilic stippling on peripheral smear. Blood lead level is markedly elevated. Lead impairs heme synthesis chiefly by inhibiting which two enzymes?
- A ALA synthase and ALA dehydratase
- B Ferrochelatase and uroporphyrinogen decarboxylase
- C ALA dehydratase and ferrochelatase ✓
- D Coproporphyrinogen oxidase and ALA synthase
Correct answer: C. ALA dehydratase and ferrochelatase
Explanation
Lead blocks two enzymes in the heme pathway: ALA dehydratase, which condenses ALA into porphobilinogen, and ferrochelatase, which inserts iron into protoporphyrin IX. Inhibition causes elevated ALA and free erythrocyte protoporphyrin, plus basophilic stippling from ribosomal RNA degradation. Uroporphyrinogen decarboxylase is the enzyme inhibited in porphyria cutanea tarda, and ALA synthase is not directly inhibited by lead.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.