A patient on long-term isoniazid (INH) therapy develops peripheral neuropathy. The mechanism involves which vitamin?

• A Isoniazid inhibits folate dihydroreductase, causing megaloblastic neuropathy
• B Isoniazid chelates cobalamin (B12) in the gut, reducing B12 absorption and causing subacute combined degeneration
• C Isoniazid impairs thiamine (B1) phosphorylation, inhibiting pyruvate dehydrogenase and causing lactic acidosis neuropathy
• D Isoniazid forms a hydrazone with pyridoxal phosphate (vitamin B6), depleting functional PLP and impairing PLP-dependent enzyme activity including synthesis of GABA and sphingolipid ✓

Explanation

Isoniazid (INH) is a structural analogue of pyridoxine (B6). It reacts with pyridoxal phosphate (PLP) to form pharmacologically inactive hydrazone complexes, effectively depleting cellular PLP. PLP is an essential cofactor for over 100 enzyme reactions, including amino acid transamination (GABA synthesis from glutamate), serine racemase, sphingolipid synthesis (serine palmitoyltransferase), and aminolevulinate synthase. INH-induced B6 depletion in peripheral nerves causes neuropathy. Pyridoxine supplementation (10–50 mg/day) is given prophylactically, especially in slow acetylators and malnourished patients.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.