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

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Propanoyl-CoA Leucine, isoleucine and valine metabolism Succinate Tricarboxylic acid (TCA) cycle