Glutamate metabolism

Glutamate and glutamine are non-essential amino acids in both Toxoplasma gondii and Plasmodium falciparum as in humans. Both organisms possess NAD+-specific (1.4.1.2) and NADP+-specific (1.4.1.4, 2 isoforms in P. falciparum and 1 in T. gondii) glutamate dehydrogenases that catalyse reversible conversion of glutamate to 2-oxoglutarate. The metabolic pathway in MPMP (http://sites.huji.ac.il/malaria/maps/glutamatemetpath.html) is extended here for Toxoplasma as it possesses the capability to de novo synthesise proline from glutamate as in humans [1]. The genes for all the enzymes involved in this process are present in T. gondii gene models. The genes encoding the enzymes glutamate 5-kinase and glutamyl phosphate reductase are absent in P. falciparum genome.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Glutamate-5-semialdehyde dehydrogenase 1.2.1.41 TGME49_270550 Cytosol Previous publication
Glutamate dehydrogenase 1.4.1.2 TGME49_249390 Mitochondrion Previous publication
Glutamate dehydrogenase 1.4.1.4 TGME49_293180 Cytosol Previous publication
Pyrroline-5-carboxylate reductase 1.5.1.2 TGME49_236070 Extracellular? Previous publication
Pyrroline-5-carboxylate reductase 1.5.1.2 TGME49_271610 Apicoplast Previous publication
Glutaminyl-peptide cyclotransferase 2.3.2.5 TGME49_258020    
Aspartate transaminase 2.6.1.1 TGME49_248600 Cytosol Previous publication
Hexosephosphate aminotransferase 2.6.1.16 TGME49_231350 Apicoplast Previous publication
Glutamate 5-kinase 2.7.2.11 TGME49_265010    
Glutamyl-tRNA synthetase 6.1.1.17 TGME49_241870    
Glutamyl-tRNA synthetase 6.1.1.17 TGME49_263870 Cytosol Previous publication
Glutaminyl-tRNA synthetase 6.1.1.18 TGME49_217460 Cytosol; Mitochondrion Apiloc; Previous publication
L-glutamate ammonia ligase 6.3.1.2 TGME49_273490 Cytosol Previous publication
gamma-Glutamylcysteine synthetase 6.3.2.2 TGME49_232590    
Carbamoyl-phosphate synthase Glu synthesizing 6.3.5.5 TGME49_215260 Cytosol Previous publication
Glutamyl-tRNA(Gln) amidotransferase 6.3.5.7 TGME49_233838    

 

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

 

TGME49_002320 TGME49_014360 TGME49_018480 TGME49_034622
TGME49_061550 TGME49_068440 TGME49_068450 TGME49_071891
TGME49_111190 TGME49_111200    

 

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

 

TGME49_034617 TGME49_067110 TGME49_072220 TGME49_075820
TGME49_102030 TGME49_105170 TGME49_115200  

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
D-Fructose-6P Glycolysis Oxaloacetate Pyruvate metabolism, Tricarboxylic acid (TCA) cycle
    2-oxoglutarate Tricarboxylic acid (TCA) cycle
    gamma-glutamylcysteine Redox metabolism
    Glucosamine-6P Aminosugars metabolism
    Carbamoyl-P Pyrimidine metabolism
    L-Proline Proline metabolism