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 Cryptosporidium muris genome. The TCA cycle is absent in other Cryptosporidium species such as Cryptosporidium parvum and Cryptosporidium hominis. Comparison of C. muris pathway to the TCA cycle of Toxoplasma gondii shows that C. muris possess one isoform of citrate synthase (2.3.3.1) as opposed to 3 isoenzymes in T. gondii (two with 2.3.3.1 and other with 2.3.3.8 annotations).

 

Enzyme EC Number Gene id
Malate dehydrogenase 1.1.1.37 CMU_006400
Isocitrate dehydrogenase 1.1.1.42 CMU_033490
Malalte:quinone oxidoreductase 1.1.5.4 CMU_024300
Oxoglutarate dehydrogenase E1 subunit 1.2.4.2 CMU_035820
Succinate dehydrogenase 1.3.5.1 CMU_014010
Succinate dehydrogenase 1.3.99.1 CMU_043190
Dihydrolipoamide dehydrogenase 1.8.1.4 CMU_023430
Dihydrolipoamide S-succinyl transferase 2.3.1.61 CMU_020490
Citrate (si)-synthase 2.3.3.1 CMU_028110
Fumarate hydratase 4.2.1.2 CMU_026970
Aconitate hydratase 4.2.1.3 CMU_018780
Succinate-CoA ligase 6.2.1.4 CMU_040940
Succinate-CoA ligase 6.2.1.5 CMU_032980
Mitochondrial carrier protein none CMU_025080
Acetyl-CoA transporter none CMU_027760
Oxoglutarate/malate translocator none CMU_035290

 

Open in a new window

 

 

Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
CoA CoA biosynthesis Malate Host
    Acetyl-CoA Pyruvate metabolism, Fatty acid elongation in the cytosol, Fatty acid elongation in the ER