Lead poisoning inhibits two specific enzymes of heme synthesis. Which two enzymes are affected, and what laboratory findings does each inhibition produce?

• A ALA synthase and ferrochelatase; elevated serum iron and elevated protoporphyrin IX
• B PBG deaminase and uroporphyrinogen III synthase; elevated PBG and coproporphyrin III
• C ALA dehydratase (ALAD) and ferrochelatase; elevated urinary ALA and elevated zinc protoporphyrin IX (ZPP) ✓
• D Ferrochelatase and uroporphyrinogen decarboxylase; elevated protoporphyrin IX and uroporphyrin

Explanation

Lead inhibits two sulfhydryl-containing enzymes in heme synthesis: (1) ALA dehydratase (ALAD, condenses two ALA molecules to PBG) — its inhibition raises urinary ALA; and (2) ferrochelatase — its inhibition prevents iron insertion into protoporphyrin IX, causing accumulation of protoporphyrin IX which chelates zinc instead of iron, producing elevated zinc protoporphyrin (ZPP). ZPP is the standard screening test for lead poisoning and iron deficiency. The resultant microcytic anemia with basophilic stippling (ribosomal aggregation from inhibited 5'-pyrimidine nucleotidase) is characteristic.

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

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