Thiamine pyrophosphate-glycoaldehyde

Figure 20.21. Transketolase Mechanism. The carbanion of thiamine pyrophosphate (TPP) attacks the ketose substrate. Cleavage of a carbon-carbon bond frees the aldose product and leaves a two-carbon fragment joined to TPP. This activated glycoaldehyde intermediate attacks the aldose substrate to form a new carbon-carbon bond. The ketose product is released, freeing the TPP for the next reaction cycle.

Transketolase Reaction. Transketolase contains a tightly bound thiamine pyrophosphate as its prosthetic group. The enzyme transfers a two-carbon glycoaldehyde from a ketose donor to an aldose acceptor. The site of the addition of the two-carbon unit is the thiazole ring of TPR Transketolase is homologous to the Ej subunit of the pyruvate dehydrogenase complex (p. 478) and the reaction mechanism is similar (Figure 20.21). 

Thiamine pyrophosphate is also an important cofactor for the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism (Fignre 15-3). These reactions are important in the reversible transformation of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring of TPP that reacts with a ketose phosphate (xylnlose 5-phosphate) to canse the release of an aldose phosphate with two fewer carbons (glyceraldehyde 3-phosphate). The TPP-bonnd glycoaldehyde unit is then transferred to a different aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or fructose 6-phosphate). 

This enzyme catalyzes the reversible transfer of the hydroxyketo group of a ketose phosphate to an aldose phosphate. The cofactor thiamine pyrophosphate (TPP) is associated with the enzyme and activates the ketose (Scheme 7). Most known donor ketoses (xylulose 5-phosphate, sedoheptulose 7-phosphate, fructose 6-phosphate, L-erythrose) have a trans arrangement of hydroxy groups at C-3 and C-4 hydroxypyruvate is an exception. A range of aldehydes (such as o-glyceraldehyde 3-phosphate, D-ribose 5-phosphate, o-erythrose 4-phosphate, glycoaldehyde) are acceptors. Transketolase has been... 

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