Trivalent arsenic (arsenite) poisoning leads to accumulation of pyruvate and alpha-ketoglutarate in tissues. The molecular basis is:
- A Competitive inhibition of NAD+ binding sites on dehydrogenases
- B Inhibition of lipoamide-containing enzymes by binding vicinal sulfhydryl groups ✓
- C Irreversible inhibition of cytochrome oxidase
- D Chelation of the iron-sulfur clusters of aconitase
Correct answer: B. Inhibition of lipoamide-containing enzymes by binding vicinal sulfhydryl groups
Explanation
Arsenite binds vicinal dithiols of reduced lipoamide in the dihydrolipoyl moieties of both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes, inactivating them. Substrates upstream accumulate, explaining the elevated pyruvate and alpha-ketoglutarate. Cytochrome oxidase is the target of cyanide and carbon monoxide, and aconitase iron-sulfur disruption is the mechanism of fluoroacetate-related toxicity, not arsenite.
Reference: Harper's Illustrated Biochemistry, 31st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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