A 35-year-old man develops painful ascending peripheral neuropathy with 'rain-drop pigmentation,' Mees' lines on nails, and Aldrich-Mees lines after a 6-week illness. Urine arsenic is 250 µg/L (normal <50). The mechanism of chronic arsenic toxicity causing peripheral neuropathy is:
- A Arsenic inhibits cytochrome oxidase causing mitochondrial uncoupling
- B Pentavalent arsenic substitutes phosphate in ATP synthesis, producing unstable ADP-arsenate
- C Trivalent arsenic binds lipoic acid, inhibiting pyruvate dehydrogenase and α-ketoglutarate dehydrogenase ✓
- D Arsenic competitively inhibits folate metabolism, causing axonal demyelination
Correct answer: C. Trivalent arsenic binds lipoic acid, inhibiting pyruvate dehydrogenase and α-ketoglutarate dehydrogenase
Explanation
Trivalent arsenic (As³⁺) has high affinity for vicinal thiol (dithiol) groups; it binds lipoic acid (a dithiol cofactor), thereby inhibiting pyruvate dehydrogenase and α-ketoglutarate dehydrogenase — both require lipoic acid. This blocks energy production and causes neuropathy. Pentavalent arsenic does cause arsenolysis (ADP-arsenate formation), but it is the trivalent form that underlies the classic peripheral neuropathy. Mees' lines result from matrix arrest during acute poisoning.
Reference: The Essentials of Forensic Medicine and Toxicology (Narayan Reddy), 34th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.