A 55-year-old man treated for tuberculosis develops anemia with MCV 102 fL. Bone marrow shows erythroid hyperplasia with ring sideroblasts. Which enzyme step is blocked by the offending drug?

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

Explanation

Isoniazid interferes with pyridoxine (vitamin B6) function, and B6 is the cofactor for ALA synthase, the first and rate-limiting step of heme synthesis. Blockade causes iron to accumulate in mitochondria, forming ring sideroblasts. Ferrochelatase inhibition is the lead poisoning mechanism, ALA dehydratase blockade also occurs in lead toxicity, and uroporphyrinogen decarboxylase defects cause porphyria cutanea tarda, none of which match this drug exposure.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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