A 40-year-old woman on long-term isoniazid and hydralazine therapy develops a peripheral neuropathy with sensory loss and burning pain. Her symptoms partially respond to pyridoxine. What is the precise biochemical mechanism by which these drugs cause pyridoxine (B6) deficiency?
- A Both drugs form hydrazones with pyridoxal phosphate (PLP), inactivating it and markedly increasing urinary excretion of vitamin B6 ✓
- B Isoniazid inhibits pyridoxal kinase, preventing phosphorylation of pyridoxine to PLP
- C Hydralazine competitively inhibits PLP-dependent aminotransferases by occupying their active sites
- D Both drugs block intestinal absorption of pyridoxine by inhibiting the PLP transporter
Explanation
Isoniazid and hydralazine both contain hydrazide/hydrazine moieties that react with the aldehyde group of pyridoxal phosphate (PLP) to form stable Schiff base (hydrazone) adducts. These adducts are pharmacologically inactive and rapidly excreted in urine, drastically depleting functional PLP. Since PLP is the active cofactor for over 100 enzymes including amino acid decarboxylases and aminotransferases, its depletion causes peripheral neuropathy, pellagra-like symptoms, and hypochromic anemia. Prophylactic pyridoxine (25–50 mg/day) is co-prescribed to prevent this complication.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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