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.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
6-phosphogluconate dehydrogenase 1.1.1.44 TGME49_242600    
6-phosphogluconate dehydrogenase 1.1.1.44 TGME49_307850 Cytosol Previous publication
Glucose-6P dehydrogenase 1.1.1.49 TGME49_294200 Extracellular? Previous publication
Bifunctional glucose-6P dehydrogenase/6-phosphoglucolactonase 1.1.1.49; 3.1.1.31 TGME49_278830 Cytoplasm-nuclear Previous publication
Transketolase 2.2.1.1 TGME49_318310 Nucleus Previous publication
Transaldolase 2.2.1.2 TGME49_229360 Cytosol Previous publication
Ribokinase 2.7.1.15 TGME49_305030 Nucleus Previous publication
Ribosephosphate pyrophosphokinase 2.7.6.1 TGME49_220100 Nucleus Previous publication
Ribosephosphate pyrophosphokinase 2.7.6.1 TGME49_284580    
ADP-ribose diphosphatase 3.6.1.13 TGME49_282190    
Deoxyribose-phosphate aldolase 4.1.2.4 TGME49_270650 Cytosol Previous publication
Deoxyribose-phosphate aldolase 4.1.2.4 TGME49_318750    
Ribulose-phosphate 3-epimerase 5.1.3.1 TGME49_247670 Extracellular? Previous publication
Ribosephosphate isomerase 5.3.1.6 TGME49_239310 Cytosol Previous publication
Phosphoglucomutase 5.4.2.2 TGME49_285980 Cytosol; Apical Apiloc; Previous publication
Phosphoglucomutase 5.4.2.2 TGME49_318580 Cytosol; Mitochondrion Apiloc; Previous publication

 

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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