Lead poisoning inhibits two enzymes in heme synthesis: delta-aminolevulinate dehydratase (ALAD) and ferrochelatase. The resulting accumulation of protoporphyrin IX (measured as erythrocyte protoporphyrin or EP/ZPP) is used as a screening test. Which laboratory finding is specifically caused by ALAD inhibition?
- A Elevated urinary coproporphyrin III
- B Elevated urinary ALA with normal PBG ✓
- C Ringed sideroblasts in bone marrow
- D Elevated erythrocyte protoporphyrin (ZPP)
Explanation
ALAD (delta-aminolevulinate dehydratase) condenses 2 ALA → porphobilinogen (PBG). Lead's inhibition of ALAD causes upstream ALA accumulation — urine ALA is elevated. Since PBG synthesis is blocked, urine PBG is normal or low (distinguishing lead poisoning from acute porphyria where both ALA and PBG are elevated). Ferrochelatase inhibition (also by lead) blocks heme production, causing protoporphyrin IX to accumulate and chelate zinc instead of iron → zinc protoporphyrin (ZPP, erythrocyte protoporphyrin — option D). Ringed sideroblasts (option C) are characteristic of sideroblastic anemia from lead poisoning via ALA synthase in mitochondria but are a histological rather than biochemical finding specific to ALAD inhibition.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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