Subject thiamin diphosphate

The role of thiamin diphosphate in pymvate dehydrogenase means that, in deficiency, there is impaired conversion of pymvate to acetyl GoA, and hence impaired entry of pymvate into the citric acid cycle. Especially in subjects on a relatively high carbohydrate diet, this results in increased plasma concentrations oflactate and pymvate, which may lead to life-threateninglactic acidosis. 

The decarboxylation and oxidation of pyruvate to form acetyl CoA requires the coenzyme thiamin diphosphate, which is formed from vitamin (section 11.6.2). In thiamin deficiency, this reaction is impaired, and deficient subjects are unable to metabolize glucose normally. Especially after a test dose of glucose or moderate exercise they develop high blood concentrations of pyruvate and lactate. In some cases this may be severe enough to result in life-threatening acidosis. 

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