A 48-year-old man with chronic alcoholism receives an intravenous dextrose infusion and develops tachycardia, confusion and ophthalmoplegia. His plasma pyruvate and lactate are elevated. The vitamin whose deficiency explains his decompensation acts as a cofactor for which two enzymes central to this deterioration?
- A Pyruvate carboxylase and acetyl-CoA carboxylase
- B Succinyl-CoA synthetase and citrate synthase
- C Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase ✓
- D Complex I and Complex IV
Explanation
Thiamine pyrophosphate is the decarboxylation cofactor shared by pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase (and transketolase). In thiamine deficiency, a glucose load floods these two complexes with substrate they cannot process, so pyruvate rises, lactate rises, and vulnerable brain regions fail, giving the Wernicke picture. Giving thiamine before dextrose prevents this. Biotin-dependent carboxylases involve vitamins unrelated to this presentation.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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