Thiamine pyrophosphate (TPP) is derived from thiamine (vitamin B1) via an ATP-dependent pyrophosphorylation. TPP is the coenzyme for all decarboxylations of -keto acids. Steps in the process are depicted in Figure 14.6, summarized below.

1. Carbanion formation on the thiazole portion of TPP.

2. Carbanion attack on the carbonyl-carbon of -keto acids to yield an addition compound. In Figure 14.6, the -keto acid is pyruvate.

3. Decarboxylation of the addition compound with the thiazole ring acting as an electron sink in forming a resonance-stabilized eneamine.

4. Protonation of the eneamine to form an active acetaldehyde called hydroxyethyl-TPP.

5. The active acetaldehyde can then be oxidized (as in the pyruvate dehydrogenase and -ketoglutarate dehydrogenase complexes) or an elimination reaction (non-oxidative) can occur. In either case, the decarboxylated compound is released, yielding free TPP.

Thus, TPP functions to form an activated aldehyde species which may or may not be subsequently oxidized.

-Ketoglutarate Dehydrogenase Complex