Exposure to which element disrupts the PDH complex?

Exposure to which element disrupts the PDH complex?

• A. Arsenic
• B. Mercury
• C. Lead
• D. Cadmium

Answer: (A)

PDH relies on a lipoamide cofactor on the E2 subunit to shuttle the acetyl group from pyruvate to CoA. Arsenic, especially inorganic arsenite, binds strongly to sulfhydryl groups and targets the reduced lipoamide arm, forming stable As–S bonds. This locks the lipoamide in a nonfunctional state and prevents reoxidation, effectively halting the transfer of the acetyl group and stopping pyruvate oxidation. The result is impaired acetyl-CoA formation and reduced NADH production, compromising cellular energy production. Other metals can cause toxicity through various targets, but arsenic uniquely disrupts PDH via this lipoamide interaction, making it the correct element in this context.

PDH relies on a lipoamide cofactor on the E2 subunit to shuttle the acetyl group from pyruvate to CoA. Arsenic, especially inorganic arsenite, binds strongly to sulfhydryl groups and targets the reduced lipoamide arm, forming stable As–S bonds. This locks the lipoamide in a nonfunctional state and prevents reoxidation, effectively halting the transfer of the acetyl group and stopping pyruvate oxidation. The result is impaired acetyl-CoA formation and reduced NADH production, compromising cellular energy production. Other metals can cause toxicity through various targets, but arsenic uniquely disrupts PDH via this lipoamide interaction, making it the correct element in this context.