The function of pyruvate decarboxylase is two-fold: 1) the conversion of pyruvate to hydroxyethyl-TPP with the elimination of a carbon dioxide molecule, and 2) to transfer the hydroxyethyl group attatched to TPP to the lipoamide from the E2 component of the pyruvate dehydrogenase complex, dihydrolipoyl transacetylase. This transfer ultimately brings pyruvate decarboxylase back to its native form, ready to catalyze the next reaction. This reaction takes place in the mitochondrial matrix.
The importance of the prosthetic group, thiamine pyrophosphate (TPP), is key to the reaction mechanism. TPP is not only the prosthetic group of pyruvate decarboxylase, but it is also at the center of the active site. The carbon atom between the sulfur and nitrogen atoms of the thiazole ring in TPP acts as a carbanion which readily binds the pyruvate. This intermediate is converted to a more stable form by the decarboxylation of pyruvate. The result is hydroxyethyl-TPP.
Pyruvate + Thiamine PyroPhosphate (TPP) -----> Hydroxyethyl-TPP + CO2
The next step is to regenerate the native form of TPP. The hydroxyethyl-TPP is oxidized by the disulfide group of lipoamide from dihydrolipoyl transacetylase(E2). The acetyl group is transferred from the TPP component of pyruvate decarboxylase to the lipoamide component of E2, yielding acetyllipoamide. The TPP from pyruvate decarboxylase is then returned to its native form.
Hydroxyethyl-TPP + Lipoamide -----> Thiamine Pyrophosphate + Acetyllipoamide
A disease related to the deficiency of TPP (Vitamin B1) is called beriberi. This deficiency inhibits the ability of pyruvate decarboxylase to oxidize pyruvate. The lack of energy being produced in nervous tissues leads to brain damage.