Thiamine Pyrophosphate and Decarboxylations

Thiamine pyrophosphate (TPP) is derived from thiamine (vitamin B 1) 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.

See also: Thiamine Pyrophosphate, Pyruvate Dehydrogenase Complex, -Ketoglutarate Dehydrogenase Complex