Metabolism
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Life-threatening acidosis in an alcoholic - and in a hunger striker given intravenous glucose
Key points from this exercise:
Thiamin, as thiamin diphosphate, is required for the oxidation of pyruvate. In thiamin deficiency there is (potentially life-threatening) acidosis due to elevated plasma concentrations of lactate and pyruvate, especially after a glucose load and moderate exercise.
Pyruvate is oxidised to acetyl CoA by a multi-enzyme complex, in which the following sequence of reactions occurs:
Pyruvate reacts with enzyme-bound thiamin diphosphate, undergoing decarboxylation to hydroxy-ethyl thiamin diphosphate.
The hydroxy-ethyl group is transferred to enzyme-bound lipoamide, forming acetyl lipoamide.
The acetyl group s transferred onto coenzyme A, forming acetyl CoA, and leaving reduced lipoamide at the active site of the enzyme.
Reduced lipoamide is reoxidised by reaction with NAD.