Glycine, serine and cysteine metabolism

Toxoplasma gondii possesses the ability to synthesise glycine, serine and cysteine. Toxoplasma can synthesise serine with glycerate/glycerate-3-phosphate as the substrate. The Toxoplasma genome has 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) suggests that it can inter-convert serine into cysteine as in humans and in other animals. However, it has been suggested that Toxoplasma possesses an auxotrophic requirement for cysteine before [1]. These observations have led to the extension of glycine and serine metabolism pathway in MPMP into glycine, serine and cysteine metabolism pathway for Toxoplasma.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Glycerate dehydrogenase 1.1.1.29 TGME49_214760 Extracellular? Previous publication
Phosphoglycerate dehydrogenase 1.1.1.95 TGME49_239820 Cytosol Previous publication
Glycine dehydrogenase 1.4.4.2 Missing in annotation    
Dihydrolipoyl dehydrogenase 1.8.1.4 TGME49_206470 Mitochondrion Apiloc; Previous publication
Dihydrolipoyl dehydrogenase 1.8.1.4 TGME49_305980 Apicoplast Apiloc; Previous publication; Orthology transformation from P. falciparum
Serine hydroxymethyltransferase 2.1.2.1 TGME49_234190 Cytoskeleton Previous publication
Aminomethyltransferase 2.1.2.10 TGME49_237470 Mitochondrion Previous publication
Aminomethyltransferase 2.1.2.10 TGME49_283820    
5-aminolevulinate synthase 2.3.1.37 TGME49_258690    
Asparate transaminase 2.6.1.1 TGME49_248600 Cytosol Previous publication
Serine/pyruvate transaminase 2.6.1.51 TGME49_239530 Cytosol Previous publication
Phosphoserine transaminase 2.6.1.52 TGME49_218780 Cytosol Previous publication
Glycerate kinase 2.7.1.31 TGME49_244150 Nucleus Previous publication
3-mercaptopyruvate sulfurtransferase 2.8.1.2 TGME49_305910 Extracellular? Previous publication
Phosphoserine phosphatase 3.1.3.3 TGME49_222900    
Cystathionine beta-synthase 4.2.1.22 TGME49_259180    
Cystathionine gamma-lyase 4.4.1.1 TGME49_312930    
Serine-tRNA ligase 6.1.1.11 TGME49_251690 Apicoplast Previous publication
Serine-tRNA ligase 6.1.1.11 TGME49_271625 Apicoplast Apiloc
Glycine-tRNA ligase 6.1.1.14 TGME49_254200    
Glycine-tRNA ligase 6.1.1.14 TGME49_256990 Apicoplast Previous publication
Cysteine-tRNA ligase 6.1.1.16 TGME49_299810 Apicoplast Apiloc; Previous publication

 

List of genes annotated as tRNA-Gly in T. gondii genome

 

TGME49_002660 TGME49_002670 TGME49_028075 TGME49_046680
TGME49_055230 TGME49_057386 TGME49_077960 TGME49_088755
TGME49_088760 TGME49_088765 TGME49_088770 TGME49_094100
TGME49_101999      

 

List of genes annotated as tRNA-Ser in T. gondii genome

 

TGME49_007365 TGME49_007380 TGME49_007810 TGME49_008480
TGME49_020620 TGME49_054100 TGME49_075340 TGME49_088980
TGME49_100634 TGME49_101997 TGME49_110875 TGME49_110880
TGME49_119330      

 

List of genes annotated as tRNA-Cys in T. gondii genome

 

TGME49_057383 TGME49_082100 TGME49_082110 TGME49_082120
TGME49_100637 TGME49_105505    

 

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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?