Which element interferes with the PDH complex?

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

Answer: (A)

The PDH complex converts pyruvate from glycolysis into acetyl-CoA to feed the TCA cycle, and its activity relies on the lipoic acid-containing arm of the E2 subunit. Arsenic, particularly in its inorganic form, targets this area by binding to the sulfhydryl groups of the lipoamide cofactor. This covalent interaction blocks the transfer of the acetyl group, effectively shutting down PDH (and related dehydrogenases that use the same lipoyl cofactor). With PDH inhibited, pyruvate accumulates and is shunted to lactate, leading to impaired energy production and potential lactic acidosis. The other elements tend to disrupt different processes—lead mainly affects heme synthesis, mercury reacts broadly with thiol groups and can impair multiple enzymes, and cadmium has other toxic targets—whereas arsenic’s interference with the lipoyl arm of PDH is the classic mechanism affecting this complex.