A farmer accidentally ingests a rodenticide containing sodium fluoroacetate (compound 1080). In the mitochondrion, fluoroacetate is converted to fluorocitrate, which accumulates and causes citrate levels to rise sharply. Fluorocitrate acts as a suicide inhibitor of which TCA cycle enzyme?
- A Citrate synthase
- B Isocitrate dehydrogenase
- C Aconitase ✓
- D Alpha-ketoglutarate dehydrogenase
Correct answer: C. Aconitase
Explanation
Fluoroacetate condenses with oxaloacetate to form fluorocitrate, a potent suicide substrate of aconitase, blocking the conversion of citrate to isocitrate. The result is citrate accumulation with failure of the cycle beyond the first step. Citrate synthase is not blocked; it keeps forming citrate, which is why citrate rises. Isocitrate and alpha-ketoglutarate dehydrogenases act downstream and are not the direct targets.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.