Tricarboxylic acid (TCA) cycle
Tricarboxylic acid cycle also called citrate cycle and Krebs cycle is the third step in aerobic respiration. In eukaryotes, this process takes place in the mitochondrial matrix. It utilises acetyl-CoA from pyruvate oxidation or fatty acid/protein degradation as substrate. In addition, each cycle utilises 2 H2O molecules and generates CO2 and coenzyme-A. This is a cycle of eight enzymes catalysing nine reactions where oxaloacetate, which reacts with acetyl-CoA in the first step, is replenished in the last step. The reverse of this cycle called reverse or reductive Krebs cycle also occurs in some bacteria which utilises CO2 and H2O to synthesise carbon compounds.
Genes for all the enzymes of this pathway are present in the Neospora caninum genome as in Toxoplasma gondii. Almost all of these enzymes are targeted to mitochondrion (either experimentally or bioinformatics predictions) in T. gondii [1, 2]. The only enzyme which is present in T. gondii and N. caninum and absent in Plasmodium falciparum is 22.214.171.124. Although the pyruvate dehydrogenase complex is present in the apicoplast in apicomplexans such as N. caninum, P. falciparum and T. gondii , the presence of complete pathways which catalyse generation of acetyl-CoA from fatty acids (fatty acid recycling and degradation) and branched chain amino acids (leucine, isoleucine and valine metabolism) suggests possible sources of acetyl-coA for Krebs cycle. This also suggests possible role of Krebs cycle in energy generation in at least some life cycle stages of T. gondii and N. caninum. The presence of anaplerotic enzymes which replenish oxaloacetate such as pyruvate carboxylase and PEP carboxykinase (pyruvate metabolism) suggests that Krebs cycle also has role in biosynthetic pathways. For more details on any available experimental evidence in Apicomplexa, refer to the TCA cycle pathway page for T. gondii.
|Enzyme||EC Number||Gene id|
|Isocitrate dehydrogenase (ICDH2)||126.96.36.199||NCLIV_056480|
|Malate dehydrogenase (Quinone)||188.8.131.52 (Entry changed to 184.108.40.206)||NCLIV_040970|
|Oxoglutarate dehydrogenase E1 subunit (part of oxoglutarate dehydrogenase complex)||220.127.116.11||NCLIV_018800|
|Dihydrolipoamide dehydrogenase (part of oxoglutarate dehydrogenase complex)||18.104.22.168||NCLIV_044200|
|Dihydrolipoamide S-succinyl transferase (part of oxoglutarate dehydrogenase complex)||22.214.171.124||NCLIV_061040|
|Amino acid transporter||none||NCLIV_043960|
|Mitochondrial carrier protein||none||NCLIV_065050|
Sources and fates of metabolites
|Substrate||Source pathways||Product||Fate pathways|
|CoA||Pantothenate and CoA biosynthesis||Malate||Host|
|Glutamate||Glutamate metabolism||Acetyl-CoA||Pyruvate metabolism, Tricarboxylic acid (TCA) cycle, Fatty acid elongation in the cytosol, Fatty acid elongation in the ER|