Pentose phosphate cycle

Pentose phosphate cycle, also called as phosphogluconate pathway and hexose monophosphate shunt is important 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. Complete pentose phosphate cycle is present in both Plasmodium falciparum and Toxoplasma gondii.

 

This pathway is required for the recycling of reducing equivalents in Theileria and Babesia and therefore the oxidative phase of this pathway is present. Theileria and Babesia synthesise pyrimidine de novo and therefore this pathway is required for the generation of PRPP. The shikimate biosynthetic pathway present in P. falciparum and T. gondii is absent in Theileria and Babesia and therefore the non-oxidative phase involved in the generation of erythrose 4-phosphate is absent.

 

Enzyme EC Number Gene id
6-phosphogluconate dehydrogenase 1.1.1.44 TA19350
Bifunctional glucose-6P dehydrogenase/6-phosphoglucolactonase 1.1.1.49; 3.1.1.31 TA05220
Ribosephosphate pyrophosphokinase 2.7.6.1 TA16730
ADP-ribose diphosphatase 3.6.1.13 TA10150
Ribosephosphate isomerase 5.3.1.6 TA18725

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
D-Glucose-6P Glycolysis PRPP Pyrimidine metabolism