The pyruvate metabolism pathway for Neospora caninum is same as the pathway for Toxoplasma gondii. The pathway of pyruvate metabolism in T. gondii and N. caninum has four separate components, of which the first three are present in Plasmodium falciparum.
- Pyruvate oxidation into acetyl-CoA – There are two isoforms of the enzyme pyruvate kinase in P. falciparum, T. gondii and N. caninum, one of which targets to apicoplast. In addition, the phosphoenolpyruvate/phosphate transporter is also localised to apicoplast membrane, which transports PEP to apicoplast. The pyruvate dehydrogenase complex is also present in apicoplast suggesting that oxidation of pyruvate to acetyl-CoA takes place in apicoplast .
- 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 (Toxoplasma, Neospora and Plasmodium), PEP carboxylase (Plasmodium) and pyruvate carboxylase (Toxoplasma and Neospora) 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. The enzymes aspartate transaminase and malate dehydrogenase present in Plasmodium, Neospora and Toxoplasma can convert oxaloacetate into 2-oxoglutarate and malate respectively which are intermediates of citrate cycle.
- Acetyl-CoA synthase and acetyltransferases - Acetyl-CoA synthase, acetate-CoA ligase, acetyl-CoA C-acetyltransferase, acetoacetyl-CoA reductase and peptide alpha-N-acetyltransferase are the other enzymes of this pathway present in both Coccidia and Plasmodium species.
- Alanine synthesis – The enzymes alanine dehydrogenase and alanine transaminase which catalyse alanine biosynthesis from pyruvate in a single step are present in T. gondii and N. caninum. It is a metabolic capability unique to these Coccidians and absent in other apicomplexans. The only difference between T. gondii and N. caninum in this branch of the pathway is the copy number variation of alanine dehydrogenase enzyme (2 in T. gondii and 3 in N. caninum).
|Enzyme||EC Number||Gene id|
|Pyruvate dehydrogenase E1 beta subunit (part of pyruvate dehydrogenase complex)||126.96.36.199||NCLIV_034990|
|Pyruvate dehydrogenase E1 alpha subunit (part of pyruvate dehydrogenase complex)||188.8.131.52||NCLIV_062940|
|Dihydrolipoyl dehydrogenase (part of pyruvate dehydrogenase complex)||184.108.40.206||NCLIV_070190|
|Dihydrolipoamide S-acetyltransferase (part of pyruvate dehydrogenase complex)||220.127.116.11||NCLIV_044290|
|Acetate-CoA ligase/Acetyl-CoA synthetase||18.104.22.168; 22.214.171.124||NCLIV_032540|
|Acetate-CoA ligase/Acetyl-CoA synthetase||126.96.36.199; 188.8.131.52||NCLIV_039400|
Sources and fates of metabolites
|Substrate||Source pathways||Product||Fate pathways|
|Pyruvate||Glycolysis||2-oxoglutarate||Tricarboxylic acid (TCA) cycle, Glutamate metabolism|
|L-Glutamate||Glutamate metabolism||Aspartate||Aspartate and asparagin metabolism|
|Acetyl-CoA||Tricarboxylic acid (TCA) cycle, Fatty acid recycling and degradation, Leucine, isoleucine and valine metabolism||Acetyl-CoA||Fatty acid elongation in the cytosol, Fatty acid elongation in the ER, Fatty acid biosynthesis in the Apicoplast|