A 4-year-old boy with pica and developmental delay has Hb 9.1 g/dL, MCV 72 fL, and basophilic stippling on peripheral smear. Free erythrocyte protoporphyrin is elevated. Which enzyme step is inhibited by the toxin involved?

• A ALA synthase in the mitochondrion
• B Coproporphyrinogen oxidase
• C Uroporphyrinogen decarboxylase
• D ALA dehydratase and ferrochelatase ✓

Explanation

Lead inhibits two heme synthesis enzymes: ALA dehydratase in the cytosol and ferrochelatase, which inserts iron into protoporphyrin. Blockade at ferrochelatase leaves unincorporated protoporphyrin, raising free erythrocyte protoporphyrin, and produces ringed sideroblasts plus coarse basophilic stippling (ribosomal aggregates). Uroporphyrinogen decarboxylase is the enzyme defective in porphyria cutanea tarda, a distinct entity.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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