A farmer is brought to hospital after accidental ingestion of a rodenticide containing sodium fluoroacetate ('1080'). Metabolic analysis of his blood shows massive accumulation of citrate. Fluoroacetate causes this pattern because its metabolite inhibits which TCA cycle enzyme?
- A Alpha-ketoglutarate dehydrogenase
- B Aconitase ✓
- C Succinate dehydrogenase
- D Citrate synthase
Correct answer: B. Aconitase
Explanation
Fluoroacetate is converted to fluoroacetyl-CoA, condenses with oxaloacetate to form fluorocitrate, and fluorocitrate is a potent inhibitor of aconitase, the enzyme converting citrate to isocitrate. Citrate therefore accumulates. Citrate synthase is upstream of the block and remains active, so its product piles up rather than falling. This is the classic example of a 'suicide substrate' acting through a toxic metabolite.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.