Pentose phosphate cycle

Pentose phosphate cycle, also called as phosphogluconate pathway and hexose monophosphate shunt is important for Neospora caninum 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 Plasmodium falciparum, Toxoplasma gondii and N. caninum. The pathway here is same as the pathway for T. gondii.

 

Enzyme EC Number Gene id
6-phosphogluconate dehydrogenase 1.1.1.44 NCLIV_017630
6-phosphogluconate dehydrogenase 1.1.1.44 NCLIV_060600
Glucose-6P dehydrogenase 1.1.1.49 NCLIV_000940
Glucose-6P dehydrogenase 1.1.1.49 NCLIV_068740
Bifunctional glucose-6P dehydrogenase/6-phosphoglucolactonase 1.1.1.49; 3.1.1.31 NCLIV_067180
Transketolase 2.2.1.1 NCLIV_011210
Transaldolase 2.2.1.2 NCLIV_030290
Ribokinase 2.7.1.15 NCLIV_001280
Ribosephosphate pyrophosphokinase 2.7.6.1 NCLIV_012230
Ribosephosphate pyrophosphokinase 2.7.6.1 NCLIV_015140
ADP-ribose diphosphatase 3.6.1.13 NCLIV_023800
Deoxyribose-phosphate aldolase 4.1.2.4 NCLIV_010810
Deoxyribose-phosphate aldolase 4.1.2.4 NCLIV_036120
Ribulose-phosphate 3-epimerase 5.1.3.1 NCLIV_065340
Ribosephosphate isomerase 5.3.1.6 NCLIV_015970
Phosphoglucomutase 5.4.2.2 NCLIV_010960
Phosphoglucomutase 5.4.2.2 NCLIV_014450

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
D-Glucose-6P Glycolysis D-Erythrose-4P Shikimate biosynthesis
D-Glyceraldehyde-3P Glycolysis D-Glyceraldehyde-3P Glycolysis
D-Fructose-6P Glycolysis D-Fructose-6P Glycolysis
D-Ribose-1P Purine metabolism PRPP Purine metabolism, Pyrimidine metabolism, Nicotinate and nicotinamide metabolism