A 4-year-old boy living in an old house with flaking paint has abdominal colic, constipation, and a peripheral smear showing coarse basophilic stippling. Lead inhibits two enzymes of heme synthesis. Inhibition of which enzyme directly prevents incorporation of iron into the porphyrin ring?

• A ALA dehydratase
• B Uroporphyrinogen decarboxylase
• C ALA synthase
• D Ferrochelatase (heme synthase) ✓

Explanation

Ferrochelatase catalyzes insertion of ferrous iron into protoporphyrin IX in the mitochondrion. Lead inhibits it along with ALA dehydratase, producing sideroblastic erythropoiesis, basophilic stippling, and a raised free erythrocyte protoporphyrin. ALA dehydratase inhibition instead causes accumulation of delta-aminolevulinic acid, responsible for the neurotoxic and abdominal effects, which is why option A is tempting but answers a different step. Uroporphyrinogen decarboxylase is the enzyme deficient in porphyria cutanea tarda.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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