Question

5. Look at the transaldolase mechanism in the Pentose Phosphate Pathway. What role does the Schiff base play in this mechanism?

Answer 1

Pentose phosphate pathway is a source of NADPH, in all organsims, to use in reductive biosynthesis. It has 2 phases: Oxidative generation of NADPH and the nonoxidative interconversion of sugars.

NADPH is generated in the oxidative phase, when glucose 6-phosphate is oxidized to ribose 5-phosphate.

In the nonoxidative phase, there is catalysis of interconversion of 3, 4, 5, 6 and seven-carbon sugars in a series of nonoxidative reactions that results in the synthesis of five-carbon sugars for nucleotide biosynthesis.

In the pathway (Please refer the pathway), there is a transketolase and a transaldolase mechanism, both of which are distinct yet similar in many ways.

In the transketolase pathway, 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 then attacks the aldose substrate to form a new carbon-carbon bond. The ketose product is released, freeing the TPP for the next reaction cycle.

In the Transaldolase pathway, the reaction begins with the formation of a Schiff base between a lysine residue in transaldolase and the ketose substrate. Protonation of the Schiff base leads to release of the aldose product, leaving a three-carbon fragment attached to the lysine residue. This intermediate adds to the aldose substrate to form a new carbon-carbon bond. The reaction cycle is completed by release of the ketose product from the lysine side chain.

Here, the ketose product is released by hydrolysis of the Schiff base. The nitrogen atom of the protonated Schiff base plays the same role in transaldolase as the thiazole-ring nitrogen atom does in transketolase.