A patient on isoniazid and hydralazine develops pellagra-like dermatitis, despite adequate dietary niacin. The biochemical mechanism involves:
- A Hydralazine chelates NAD+ preventing its use as a coenzyme
- B Isoniazid-induced PLP deficiency impairs kynurenine pathway conversion of tryptophan to niacin ✓
- C Both drugs increase urinary excretion of niacin metabolites
- D Hydralazine inhibits niacin phosphoribosyltransferase
Explanation
The kynurenine pathway converts tryptophan to NAD+ (60 mg tryptophan → 1 mg niacin). The key enzyme kynureninase (and others in this pathway) requires PLP as a cofactor. Isoniazid (INH) depletes functional PLP by forming hydrazones with pyridoxal, which also competitively inhibits pyridoxal kinase. PLP deficiency impairs kynurenine aminotransferase and kynureninase activity, blocking the tryptophan → niacin pathway and causing functional niacin deficiency (secondary pellagra). Hartnup disease also impairs tryptophan absorption causing pellagra. The dermatitis, diarrhoea and dementia of pellagra are the consequence. Hydralazine also depletes PLP by a similar mechanism.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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