Inorganic arsenic poisoning produces symptoms resembling severe thiamine deficiency. Both conditions impair the pyruvate dehydrogenase complex because arsenite:

• A Covalently modifies the sulfhydryl groups of lipoic acid bound to the E2 subunit ✓
• B Competitively inhibits binding of thiamine pyrophosphate to the E1 subunit
• C Irreversibly inhibits the FAD containing E3 subunit
• D Chelates the calcium required for the regulatory kinase

Explanation

Arsenite forms a stable bidentate adduct with the two vicinal sulfhydryl groups of reduced lipoamide on the E2 (transacetylase) subunit, preventing lipoic acid from acting as the swinging carrier of acyl groups between active sites. Thiamine deficiency starves the same complex of TPP, the prosthetic group of E1, hence the similar clinical picture of lactic acidosis and neurological dysfunction. FAD on E3 and NAD+ regeneration are not the primary targets of trivalent arsenicals.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.