TPP cofactor: pyruvate dehydrogenase (PDH)
- Links glycolysis to the TCA (tricarboxylic acid) cycle
- Thiamine pyrophosphate = the carbanion chemistry PDH needs to decarboxylate pyruvate → acetyl-CoA
- Without it pyruvate dead-ends as lactate
- Deficiency (thiamine/B1) → lactic acidosis and Wernicke encephalopathy
- Wet beriberi; Wernicke when brain glucose can't enter the cycle
Drugs with this mechanism (1)
- Thiamine pyrophosphate — Active thiamine coenzyme required for carbohydrate metabolism; deficiency impairs energy production and contributes to Wernicke encephalopathy.
Self-check
- What product does PDH make from pyruvate with TPP?
Acetyl-CoA. - Where does pyruvate end up without this cofactor?
Lactate.
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