2-Methylcitrate cycle
Many organisms can provide carbon source in the form of acetyl-CoA for fatty acid biosynthesis via the tricarboxylic acid (citrate) shuttle (TCA cycle). Mitochondrial pyruvate dehydrogenase is absent and the complex is localised to the apicoplast in apicomplexans such as Plasmodium, Toxoplasma and Neospora. This suggests that the TCA cycle depends on other oxidation/degradation pathways rather than glycolysis derived pyruvate for acetyl-CoA. The enzymes for the complete Leucine, isoleucine and valine degradation pathway are present in Toxoplasma gondii and Neospora caninum genomes. The degradation of isoleucine and valine leads to the production of propionyl-CoA, which is toxic and inhibits cell growth [1]. The methyl-citrate cycle, a pathway present in bacteria and fungi can metabolise propionyl-CoA into pyruvate which can be used as a source of carbon [2]. The genes for the enzymes catalysing this 2-methylcitrate cycle is present in N. caninum as in T. gondii [3].
Enzyme | EC Number | Gene id |
---|---|---|
2-methylcitrate synthase | 2.3.3.5 | NCLIV_024780 |
2-methylisocitrate lyase | 4.1.3.30 | NCLIV_000780 |
aconitate hydratase | 4.2.1.3 | NCLIV_046260 |
2-methylcitrate dehydratase | 4.2.1.79 | NCLIV_013410 |
Pyruvate carboxylase | 6.4.1.1 | NCLIV_028990 |
Sources and fates of metabolites
Substrate | Source pathways | Product | Fate pathways |
---|---|---|---|
Propanoyl-CoA | Leucine, isoleucine and valine metabolism | Succinate | Tricarboxylic acid (TCA) cycle |
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