Pyruvate metabolism

The Piroplasma pathway of Pyruvate metabolism differs from the pathway of Plasmodium falciparum and Toxoplasma gondii in many aspects. The main difference between Piroplasma and Toxoplasma is the absence of the pyruvate dehydrogenase complex. The pathway of pyruvate metabolism in Apicomplexa has five separate components.

 

  1. Pyruvate oxidation into acetyl-CoA – In Plasmodium and Toxoplasma, pyruvate oxidation is catalysed by the pyruvate dehydrogenase complex of apicoplast. This oxidation is catalysed by the pyruvate:NADP(+) oxidoreductase in Cryptosporidia. The genes coding for both the enzymes are absent in Theileria and Babesia suggesting the absence of this capability.
  2. Anaplerotic (filling up) reactions – As the intermediates of citrate cycle are used up in biosynthetic reactions, oxaloacetate will be used up and need to be replenished. The enzymes PEP carboxykinase (both Toxoplasma and Plasmodium), PEP carboxylase (Plasmodium and Cryptosporidia) and pyruvate carboxylase (Toxoplasma) catalyse synthesis of oxaloacetate. Of these, the first two do not require energy source as they break energy rich phosphoenolpyruvate, whereas last enzyme require energy in the form of ATP. PEP carboxykinase and PEP carboxylase are present in the genome of Babesia bovis, whereas PEP carboxylase is missing in the genomes of Theileria parva and Theileria annulata. The study by Kiama et al demonstrated the presence of activities of PEP carboxykinase and pyruvate carboxylase in T. parva schizont. They also observed 11-fold higher activity of pyruvate carboxylase than PEP carboxykinase [1]. The gene for pyruvate carboxylase is missing in the gene models of all three Piroplasma species. The oxaloacetate synthesised can be converted to malate with the action of malate dehydrogenase. Malate dehydrogenase is present in Plasmodium, Toxoplasma, Neospora, Cryptosporidium, Theileria and Babesia species.
  3. Acetyl-CoA synthase and acetyltransferases - Acetyl-CoA synthase, acetate-CoA ligase, acetoacetyl-CoA reductase and peptide alpha-N-acetyltransferase are the other enzymes of this pathway present in apicomplexan species. The enzyme acetyl-CoA C-acetyltransferase is present in Babesia bovis, but missing in the gene models of Theileria species.
  4. Fermentation reactions – The genes coding for the enzymes pyruvate decarboxylase, bifunctional aldehyde/alcohol dehydrogenase and alcohol dehydrogenase are present in Cryptosporidia genomes and absent in other apicomplexan genomes including those of Piroplasma species.
  5. Alanine synthesis – The enzymes alanine dehydrogenase and alanine transaminase which catalyse alanine biosynthesis from pyruvate are present in Toxoplasma gondii and Neospora caninum. This metabolic capability is absent in Plasmodium and Cryptosporidium species. Kiama et al demonstrated relatively high activity of alanine transaminase in T. parva schizont [1]. The presence of the activity of an enzyme transaminating pyruvate to alanine was also observed in Babesia rodhaini [2]. However, the gene for alanine transaminase is missing in the gene models of Piroplasma species and not added to the pathway here.

 

Enzyme EC Number Gene id
Acetoacetyl-CoA reductase 1.1.1.36 BBOV_III007020
Peptide alpha-N-acetyltransferase 2.3.1.88 BBOV_II004010
Peptide alpha-N-acetyltransferase 2.3.1.88 BBOV_III007230
Acetyl-CoA C-acetyltransferase 2.3.1.9 BBOV_I002980
Aspartate transaminase 2.6.1.1 BBOV_III010960
Pyruvate kinase 2.7.1.40 BBOV_III010130
Phosphoenolpyruvate carboxylase 4.1.1.31 BBOV_II002090
PEP carboxykinase 4.1.1.49 BBOV_I003550
Carbonic anhydrase 4.2.1.1 BBOV_III005360
Acetate-CoA ligase/Acetyl-CoA synthetase 6.2.1.1; 6.2.1.13 BBOV_II003630
PEP/Pi translocator none BBOV_IV009970

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Phosphoenolpyruvate Glycolysis Malate Host
L-Glutamate Glutamate metabolism Aspartate Glutamate metabolism
CoA CoA biosynthesis 2-oxoglutarate Tricarboxylic acid (TCA) cycle, Glutamate metabolism
Acetyl-CoA Tricarboxylic acid (TCA) cycle Acetyl-CoA Tricarboxylic acid (TCA) cycle