A 32-year-old woman on long-term isoniazid therapy develops peripheral neuropathy with glove-and-stocking sensory loss. The biochemical mechanism by which isoniazid causes this deficiency involves:
- A Isoniazid forms a hydrazone with pyridoxal phosphate (PLP), inactivating it and increasing urinary excretion of PLP-hydrazine complexes ✓
- B Isoniazid competitively inhibits dihydrofolate reductase, impairing folate activation
- C Isoniazid depletes niacin by inhibiting tryptophan conversion to NAD+
- D Isoniazid chelates magnesium required for PLP-dependent enzyme activation
Explanation
Isoniazid is a hydrazide that forms a covalent Schiff base (hydrazone) with the aldehyde group of pyridoxal phosphate (PLP), the active form of vitamin B6. This complex is pharmacologically inactive and excreted in urine, functionally depleting PLP. Since PLP is the cofactor for transaminases, decarboxylases (including DOPA decarboxylase for neurotransmitter synthesis), and cystathionine beta-synthase, its deficiency explains both the peripheral neuropathy and occasionally elevated homocysteine. Prophylactic pyridoxine (25-50 mg/day) is co-administered with high-dose or prolonged isoniazid therapy.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.