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 2.3.3.8. Although the pyruvate dehydrogenase complex is present in the apicoplast in apicomplexans such as N. caninum, P. falciparum and T. gondii [3], 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.

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Sources and fates of metabolites