A 45-year-old man with chronic alcoholism presents with confusion, ataxia, and ophthalmoplegia. Blood shows elevated pyruvate and lactate along with raised alpha-ketoglutarate. Impaired activity of which TCA cycle enzyme best explains the elevated alpha-ketoglutarate?
- A Succinate dehydrogenase
- B Alpha-ketoglutarate dehydrogenase ✓
- C Citrate synthase
- D Malate dehydrogenase
Correct answer: B. Alpha-ketoglutarate dehydrogenase
Explanation
Thiamine pyrophosphate is a required cofactor of alpha-ketoglutarate dehydrogenase, whose structure mirrors the pyruvate dehydrogenase complex. Thiamine deficiency in alcoholism cripples both complexes, so pyruvate and alpha-ketoglutarate accumulate and are partly diverted to lactate, matching the laboratory pattern. Succinate dehydrogenase needs FAD, citrate synthase needs no vitamin cofactor, and neither explains raised alpha-ketoglutarate.
Reference: Lippincott Illustrated Reviews: Biochemistry, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.