In lead poisoning, heme synthesis is impaired at two enzymatic steps. Which enzymes are inhibited by lead, and what accumulates as a diagnostic marker in erythrocytes?

• A ALA synthase and porphobilinogen deaminase; PBG in urine
• B Uroporphyrinogen decarboxylase and heme oxygenase; coproporphyrin in feces
• C Coproporphyrinogen oxidase and ALA synthase; ALA in plasma
• D ALA dehydratase (ALAD) and ferrochelatase; zinc protoporphyrin (ZPP) in erythrocytes ✓

Explanation

Lead inhibits two sulfhydryl-dependent enzymes: (1) delta-ALA dehydratase (ALAD, porphobilinogen synthase) — inhibition causes ALA accumulation in urine; and (2) ferrochelatase — inhibition prevents iron incorporation into protoporphyrin IX, so zinc (as a surrogate metal) is incorporated instead, producing zinc protoporphyrin (ZPP). Elevated ZPP in erythrocytes (measured by fluorometry) is a sensitive clinical marker of lead toxicity and iron deficiency. Basophilic stippling of RBCs (due to ribosomal aggregation) is also characteristic.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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