Leucine, isoleucine and valine metabolism
The amino acids leucine, isoleucine and valine are essential amino acids for all apicomplexans as for humans. Coccidians such as Toxoplasma and Neospora possesses the pathway for degradation of branched chain amino acids leucine, isoleucine and valine, a pathway present in both animals and plants. This amino acids degradation pathway may well provide a source for acetyl-CoA for Krebs cycle in starving animals. The genomes of Neospora caninum and Toxoplasma gondii possess the genes for enzymes which catalyse the degradation of these branched chain amino acids into acetyl-CoA, (R)-methyl-malonyl-CoA and propionyl-CoA. The absence of mitochondrial pyruvate dehydrogenase complex suggests that this mitochondrial pathway may provide an alternative source of acetyl-CoA for TCA cycle in Neospora and Toxoplasma. Although propionyl-CoA, another product of this process is toxic, the 2-methylcitrate cycle can metabolise it to pyruvate. The only enzyme missing in N. caninum and T. gondii genomes is methylglutaconyl-CoA hydratase (4.2.1.18). Although the pathway is complete in Coccidia, Plasmodium species do not possess a complete pathway.
Enzyme | EC Number | Gene id |
---|---|---|
3-hydroxyisobutyrate dehydrogenase | 1.1.1.31 | NCLIV_034890 |
3-hydroxyacyl-CoA dehydrogenase | 1.1.1.35 | NCLIV_042220 |
Methylmalonate-semialdehyde dehydrogenase | 1.2.1.27 | NCLIV_055270 |
Aldehyde dehydrogenase | 1.2.1.3 | NCLIV_024060 |
Aldehyde dehydrogenase | 1.2.1.3 | NCLIV_040940 |
3-methyl-2-oxobutanoate dehydrogenase alpha chain (part of branched chain keto-acid dehydrogenase complex) | 1.2.4.4 | NCLIV_012850 |
3-methyl-2-oxobutanoate dehydrogenase alpha chain (part of branched chain keto-acid dehydrogenase complex) | 1.2.4.4 | NCLIV_016110 |
3-methyl-2-oxobutanoate dehydrogenase beta chain (part of branched chain keto-acid dehydrogenase complex) | 1.2.4.4 | NCLIV_057460 |
Isovaleryl-CoA dehydrogenase | 1.3.8.4 | NCLIV_020260 |
Butyryl-CoA dehydrogenase | 1.3.99.2 | NCLIV_048110 |
Dihydrolipoyl dehydrogenase (part of branched chain keto-acid dehydrogenase complex) | 1.8.1.4 | NCLIV_044200 |
2-methyl-acetoacetyl-CoA thiolase | 2.3.1.16 | NCLIV_033970 |
Dihydrolipoyl transacylase (part of branched chain keto-acid dehydrogenase complex) | 2.3.1.168 | NCLIV_010320 |
Acetyl-CoA C-acetyltransferase | 2.3.1.9 | NCLIV_069850 |
Leucyltransferase | 2.3.2.6 | NCLIV_022350 |
Branched-chain-amino-acid transaminase | 2.6.1.42 | NCLIV_006760 |
Branched-chain-amino-acid transaminase | 2.6.1.42 | NCLIV_023450 |
3-hydroxyisobutyryl-CoA hydrolase | 3.1.2.4 | NCLIV_000930 |
3-hydroxyisobutyryl-CoA hydrolase | 3.1.2.4 | NCLIV_048430 |
Hydroxymethylglutaryl-CoA lyase | 4.1.3.4 | NCLIV_020790 |
Enoyl-CoA hydratase | 4.2.1.17 | NCLIV_012140 |
Enoyl-CoA hydratase | 4.2.1.17 | NCLIV_017550 |
Enoyl-CoA hydratase | 4.2.1.17 | NCLIV_022740 |
Enoyl-CoA hydratase | 4.2.1.17 | NCLIV_054880 |
Methylglutaconyl-CoA hydratase | 4.2.1.18 | Missing in annotation |
Leucine-tRNA ligase | 6.1.1.4 | NCLIV_012860 |
Leucine-tRNA ligase | 6.1.1.4 | NCLIV_039310 |
Isoleucine-tRNA ligase | 6.1.1.5 | NCLIV_002610 |
Valine-tRNA ligase | 6.1.1.9 | NCLIV_007730 |
Valine-tRNA ligase | 6.1.1.9 | NCLIV_059740 |
Acetoacetate-CoA ligase | 6.2.1.16 | NCLIV_061250 |
Methylcrotonoyl-CoA carboxylase | 6.4.1.4 | NCLIV_036840 |
List of genes annotated as tRNA-Leu in N. caninum genome
List of genes annotated as tRNA-Ile in N. caninum genome
NC_LIV_tRNA_080005 | NC_LIV_tRNA_090001 | NC_LIV_tRNA_100006 | NC_LIV_tRNA_120009 |
NC_LIV_tRNA_140025 |
List of genes annotated as tRNA-Val in N. caninum genome
NC_LIV_tRNA_020002 | NC_LIV_tRNA_100021 | NC_LIV_tRNA_110006 | NC_LIV_tRNA_130001 |
NC_LIV_tRNA_130002 | NC_LIV_tRNA_130010 | NC_LIV_tRNA_140006 | NC_LIV_tRNA_140013 |
NC_LIV_tRNA_140021 |
Sources and fates of metabolites
Substrate | Source pathways | Product | Fate pathways |
---|---|---|---|
L-Leucine | Host | 3-hydroxyisovaleryl-CoA | Host? |
L-Isoleucine | Host | (R)-methylmalonyl-CoA | Host? |
L-Valine | Host | Propanoyl-CoA | 2-methylcitrate cycle |
2-oxoglutarate | Pyruvate metabolism, Tricarboxylic acid (TCA) cycle | L-Glutamate | Glutamate metabolism |
Thiamine diphosphate | Thiamine salvage | Acetyl-CoA | Pyruvate metabolism, Tricarboxylic acid (TCA) cycle, Fatty acid elongation in the cytosol, Fatty acid elongation in the ER |
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