Arsenite poisoning inactivates the pyruvate dehydrogenase complex by reacting with which feature of the E2 component, leading to accumulation of pyruvate and lactic acidosis?

• A The vicinal sulfhydryl groups of reduced lipoamide ✓
• B The thiamine pyrophosphate cofactor bound to E1
• C The FAD prosthetic group of E3
• D The NAD+ binding site

Explanation

Trivalent arsenicals form stable ring structures with adjacent dithiols, and the disulfide form of lipoamide on E2 (dihydrolipoyl transacetylase) provides exactly such a pair of vicinal sulfhydryl groups. Lipoamide locked in the arsenite-bound state cannot shuttle the acetyl group, halting the whole complex. Thiamine pyrophosphate is attacked instead by fluoropyruvate analogs, FAD is a flavin cofactor not targeted by arsenite, and the defect is at lipoamide rather than at the NAD+ site. Dimercaprol, itself a dithiol, rescues the enzyme by competing for the arsenic.

Reference: Lehninger Principles of Biochemistry, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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