A patient taking isoniazid, pyrazinamide, and rifampicin for TB develops pellagra-like dermatitis, diarrhoea, and dementia after 3 months. The BIOCHEMICAL mechanism linking anti-TB therapy to niacin deficiency is:

• A Isoniazid inhibits pyridoxal phosphokinase, reducing PLP, which is required for kynureninase in the tryptophan-to-niacin pathway ✓
• B Rifampicin induces CYP3A4 which degrades nicotinamide
• C Isoniazid structurally similar to pyridoxine competitively inhibits tryptophan-2,3-dioxygenase (indolamine dioxygenase), blocking the kynurenine pathway from tryptophan to NAD+
• D Pyrazinamide directly inhibits NAD synthetase, blocking niacin incorporation

Explanation

Niacin (NAD+) is synthesised endogenously from tryptophan via the kynurenine pathway in a pyridoxal-5'-phosphate (PLP)-dependent manner, specifically at the kynureninase step (kynurenine → anthranilic acid and 3-hydroxykynurenine → 3-hydroxyanthranilic acid). Isoniazid depletes hepatic PLP (as explained previously) — this blocks kynureninase, impairing endogenous niacin synthesis from tryptophan. Combined with dietary deficiency, pellagra can develop. Supplementing B6 with INH prevents both neuropathy and this pellagra-like syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.