Pellagra from niacin deficiency causes dermatitis, diarrhoea, and dementia (3 Ds). Niacin can be synthesised endogenously from tryptophan. A patient on isoniazid therapy develops pellagra despite normal dietary tryptophan intake. The mechanism is:

• A Isoniazid forms a hydrazone with pyridoxal phosphate, depleting B6 needed for tryptophan-to-niacin conversion ✓
• B Isoniazid inhibits tryptophan hydroxylase preventing niacin synthesis
• C Isoniazid induces hepatic NAD+ oxidase, increasing NAD degradation
• D Isoniazid depletes niacin by using it as a cofactor for acetylation reactions

Explanation

Isoniazid (INH) is structurally similar to pyridoxine and inhibits pyridoxine kinase; it also reacts with pyridoxal phosphate (PLP) to form an inactive hydrazone, depleting active B6. PLP is required as a cofactor for kynureninase (and kynurenine aminotransferase), which are enzymes in the tryptophan → niacin pathway. Without PLP, tryptophan cannot be converted to niacin, causing secondary pellagra. This is why prophylactic pyridoxine supplementation is given with high-dose or long-term INH therapy. Carcinoid syndrome similarly causes pellagra because tryptophan is diverted to serotonin synthesis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.