A patient on isoniazid therapy develops microcytic anemia with ringed sideroblasts on bone marrow examination. Isoniazid interferes with the function of pyridoxal phosphate (PLP) as a cofactor for which enzyme in heme biosynthesis?
- A ALA synthase (delta-aminolevulinic acid synthase) ✓
- B ALAD (delta-aminolevulinic acid dehydratase)
- C Ferrochelatase
- D Heme oxygenase
Correct answer: A. ALA synthase (delta-aminolevulinic acid synthase)
Explanation
PLP is an essential cofactor for ALA synthase, the rate-limiting enzyme in heme biosynthesis that condenses glycine and succinyl-CoA to form delta-aminolevulinic acid. Isoniazid depletes PLP, impairing heme synthesis and causing sideroblastic anemia. Ferrochelatase inserts iron into protoporphyrin and is inhibited by lead. ALAD is also inhibited by lead. Heme oxygenase degrades heme to biliverdin.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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