Pentose phosphate cycle

Pentose phosphate cycle, also called as phosphogluconate pathway and hexose monophosphate shunt is important for Toxoplasma gondii and organisms in general for three functions.

1. To recycle the reducing equivalents such as NADPH for other reductive metabolic pathways (e.g. fatty acid biosynthesis, isoprenoids biosynthesis, nitrogen metabolism, shikimate biosynthesis etc).
2. To produce ribose-5-phosphate for synthesis of PRPP, an essential substrate in pyrimidine biosynthesis.
3. To synthesise erythrose-4-phosphate an essential substrate in shikimate biosynthesis. The end product of this pathway, chorismate is important for folate biosynthesis. It is also important for the biosynthesis of aromatic amino acids, a capability which is absent in all apicomplexans.

The pathway can be divided into two phases, oxidative phase and non-oxidative phase. The first three enzymes of the pathway form the oxidative phase, where NADPH is generated and ribulose-5-phosphate is produced. All the downstream enzymes form part of second non-oxidative phase, where ribose-5-phpshate and ultimately PRPP and erythrose-4-phosphate are generated.

Pentose phosphate cycle is present in both Plasmodium falciparum and T. gondii. The pathway here is same as the pathway in MPMP. The enzyme transaldolase is missing in the P. falciparum genome, but reconstructed in MPMP pentose phosphate cycle due to biochemical evidence of functional pathway in P. falciparum [1, 2]. The differential expression of genes for the enzymes of this pathway in different time points or stages [2] also suggests the significance of different products of this pathway in various metabolic processes as mentioned above.  The gene for the enzyme transladolase is annotated to be present in T. gondii genome.

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Sources and fates of metabolites