A 35-year-old woman on long-term isoniazid therapy develops peripheral neuropathy, cheilosis, and confusion. Urinary xanthurenic acid is elevated after a tryptophan load test. What is the biochemical basis of isoniazid-induced vitamin B6 deficiency?

• A Isoniazid inhibits pyridoxal kinase, preventing phosphorylation of pyridoxal to PLP
• B Isoniazid induces CYP3A4, which hydroxylates and inactivates PLP in the liver
• C Isoniazid blocks intestinal absorption of pyridoxine at the enterocyte
• D Isoniazid forms a hydrazone with pyridoxal-5'-phosphate (PLP), inactivating it and increasing urinary excretion ✓

Explanation

Isoniazid (INH) contains a hydrazide group that condenses with the aldehyde group of pyridoxal-5'-phosphate to form an inactive hydrazone complex. This traps and inactivates PLP and also promotes its renal excretion. Since PLP is the active coenzyme for numerous transaminases, decarboxylases (including DOPA decarboxylase), and glycogen phosphorylase, its depletion causes peripheral neuropathy, seborrheic dermatitis, and altered serotonin/catecholamine synthesis. The xanthurenic acid test reflects defective kynureninase activity (PLP-dependent), confirming B6 depletion.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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