TPP is used as a coenzyme for all decarboxylations of -keto acids. It is derived from thiamine (Vitamin B1) by transfer of a pyrophosphate group from ATP to thiamine, yielding TPP and AMP.

Mechanism of action - TPP contains two heterocyclic rings, a substituted pyrimidine and a thiazole. The latter is the reactive moiety - specifically, the rather acidic carbon between the sulfur and the nitrogen. this carbon forms a carbanion (step 1 in Figure 14.6), which in turn, can attack the carbonyl carbon of -keto acids, such as pyruvate, giving an addition compound (step 2 in Figure 14.6). This compound undergoes nonoxidative decarboxylation (step 3 in Figure 14.6), with the thiazole ring acting as an electron sink in forming a resonance-stabilized ene-amine. Protonation (step 4 in Figure 14.6) gives a species called active acetaldehyde, or, more accurately, hydroxyethyl-TPP.

In the fermentation of glucose to ethanol in yeast (step 5 in Figure 14.6), this intermediate undergoes an elimination reaction to yield acetaldehyde and the TPP carbanion. In the pyruvate dehydrogenase reaction (not shown), the activated two-carbon fragment is simultaneously oxidized and transferred to another enzyme, as discussed in the section on lipoic acid. Thus, in general terms, TPP functions in the generation of an activated aldehyde species, which may or may not undergo oxidation as it is transferred to an acceptor.

Some enzymes that use TPP include pyruvate decarboxylase, pyruvate dehydrogenase, branched chain -keto acid dehydrogenase, -keto glutarate dehydrogenase, transketolase.

Thiamine Pyrophosphate and Decarboxylations, Lipoic Acid, Ethanol Fermentation, Pyruvate Dehydrogenase, Pyruvate Decarboxylase, Acetaldehyde, Ketoglutarate Dehydrogenase

1. -Keto Acid Complexes - A Review

2. Thiamine Metabolism