A 52-year-old alcoholic man presents with bilateral pretibial edema, weakness, and cardiomegaly. ECG shows sinus tachycardia. He has no proteinuria. Which thiamine-dependent enzyme deficiency underlies the cardiovascular manifestations of wet beriberi?
- A Transketolase deficiency causing impaired pentose phosphate pathway and NADPH generation
- B Alpha-ketoglutarate dehydrogenase deficiency causing TCA cycle block and GABA accumulation
- C Pyruvate dehydrogenase deficiency causing pyruvate accumulation, impaired acetyl-CoA generation, and energy failure in cardiomyocytes ✓
- D Branched-chain keto acid dehydrogenase deficiency causing lactic acidosis
Explanation
Thiamine (TPP) is essential for pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA for the TCA cycle. In wet beriberi, PDH deficiency blocks aerobic ATP generation in the high-demand myocardium and peripheral vasculature. Pyruvate accumulates and is converted to lactate (lactic acidosis). Cardiomyocytes, unable to generate sufficient ATP, dilate (high-output heart failure with peripheral vasodilation). Transketolase deficiency (also TPP-dependent) causes neurological features (Wernicke encephalopathy) while PDH deficiency primarily underlies the cardiovascular and neurological crisis of beriberi.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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