Glycine, serine and cysteine metabolism

The Coccidians Toxoplasma gondii and Neospora caninum possess the ability to synthesise glycine, serine and cysteine. Toxoplasma and Neospora can synthesise serine with glycerate/glycerate-3-phosphate as the substrate. The Toxoplasma and Neospora genomes have the genes for the enzymes glycerate kinase, phosphoglycerate dehydrogenase, phosphoserine transaminase and phosphoserine phosphatase which lead to the de novo biosynthesis of serine. This is consistent with the previous observation that Toxoplasma can synthesise serine, whereas Plasmodium has an auxotrophic requirement for serine from hosts [1]. The presence of genes for the enzymes cystathionine beta-synthase (4.2.1.22) and cystathionine gamma-lyase (4.4.1.1) in T. gondii and N. caninum suggests that it can inter-convert serine into cysteine as in humans and in other animals. But, it has been suggested that Toxoplasma possesses an auxotrophic requirement for cysteine before [1]. These have led to the extension of glycine and serine metabolism pathway in MPMP into glycine, serine and cysteine metabolism pathway for Toxoplasma and Neospora here.

 

Enzyme EC Number Gene id
Glycerate dehydrogenase 1.1.1.29 NCLIV_051810
Phosphoglycerate dehydrogenase 1.1.1.95 NCLIV_016450
Glycine dehydrogenase 1.4.4.2 Missing in annotation
Dihydrolipoyl dehydrogenase 1.8.1.4 NCLIV_044200
Dihydrolipoyl dehydrogenase 1.8.1.4 NCLIV_070190
Serine hydroxymethyltransferase 2.1.2.1 NCLIV_049400
Aminomethyltransferase 2.1.2.10 NCLIV_028840
Aminomethyltransferase 2.1.2.10 NCLIV_051210
5-aminolevulinate synthase 2.3.1.37 NCLIV_027820
Asparate transaminase 2.6.1.1 NCLIV_064760
Serine/pyruvate transaminase 2.6.1.51 NCLIV_016150
Phosphoserine transaminase 2.6.1.52 NCLIV_061600
Glycerate kinase 2.7.1.31 NCLIV_018750
3-mercaptopyruvate sulfurtransferase 2.8.1.2 NCLIV_070240
Phosphoserine phosphatase 3.1.3.3 NCLIV_005930
Cystathionine beta-synthase 4.2.1.22 NCLIV_027350
Cystathionine gamma-lyase 4.4.1.1 NCLIV_056280
Serine-tRNA ligase 6.1.1.11 NCLIV_035390
Serine-tRNA ligase 6.1.1.11 NCLIV_066770
Glycine-tRNA ligase 6.1.1.14 NCLIV_008470
Glycine-tRNA ligase 6.1.1.14 NCLIV_029970
Cysteine-tRNA ligase 6.1.1.16 NCLIV_060470

 

List of genes annotated as tRNA-Gly in N. caninum genome

 

NC_LIV_tRNA_010006 NC_LIV_tRNA_010008 NC_LIV_tRNA_010009 NC_LIV_tRNA_080003
NC_LIV_tRNA_080004 NC_LIV_tRNA_090007 NC_LIV_tRNA_090011 NC_LIV_tRNA_110002
NC_LIV_tRNA_140008 NC_LIV_tRNA_140016    

 

List of genes annotated as tRNA-Ser in N. caninum genome

 

NC_LIV_tRNA_020001

NC_LIV_tRNA_020003 NC_LIV_tRNA_020004 NC_LIV_tRNA_020007
NC_LIV_tRNA_040002 NC_LIV_tRNA_040007 NC_LIV_tRNA_050001 NC_LIV_tRNA_060003
NC_LIV_tRNA_110003 NC_LIV_tRNA_120012 NC_LIV_tRNA_130005  

 

List of genes annotated as tRNA-Cys in N. caninum genome

 

NC_LIV_tRNA_080007 NC_LIV_tRNA_090008 NC_LIV_tRNA_090009 NC_LIV_tRNA_110012

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
3-P-D-glycerate Glycolysis    
L-Glutamate Glutamate metabolism 2-oxoglutarate Tricarboxylic acid (TCA) cycle, Glutamate metabolism
2-oxoglutarate Pyruvate metabolism, Tricarboxylic acid (TCA) cycle L-Glutamate Glutamate metabolism
Alanine Alanine metabolism Pyruvate Glycolysis, Pyruvate metabolism, Alanine metabolism
Tetrahydrofolate Folate biosynthesis 5,10-methylene tetrahydrofolate Folate biosynthesis
Succinyl-CoA Tricarboxylic acid (TCA) cycle 5-aminolevulinate Porphyrin metabolism
L-homocysteine Methionine metabolism 2-oxobutanoate Host?
Sulfite Host? Thiosulfate Host?