A 30-year-old man on antitubercular therapy develops microcytic hypochromic anemia. Bone marrow shows ringed sideroblasts. Reticulocyte count is low. Which heme biosynthetic step is impaired?

• A Conversion of porphobilinogen to hydroxymethylbilane in the cytosol
• B Condensation of glycine and succinyl-CoA to delta-aminolevulinic acid in mitochondria ✓
• C Decarboxylation of uroporphyrinogen III to coproporphyrinogen III
• D Insertion of ferrous iron into protoporphyrin IX

Explanation

Isoniazid induces functional pyridoxine deficiency, and ALA synthase, the first and rate-limiting mitochondrial enzyme of heme synthesis, requires pyridoxal phosphate to condense glycine with succinyl-CoA. Its impairment causes iron accumulation around mitochondria, producing ringed sideroblasts. Ferrochelatase block (option D) causes lead poisoning, where basophilic stippling and elevated protoporphyrin distinguish it clinically.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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