Glyoxalase metabolism

The pathway map below for Toxoplasma gondii is same as the MPMP metabolic pathway of glyoxalase metabolism for Plasmodium falciparum. The orthologs of all the enzymes of this pathway in P. falciparum are also present in T. gondii. In P. falciparum, D-lactate is produced in addition to L-lactate (glycolysis). The stereo-specificity of lactate dehydrogenase suggests the possibility of D-lactate being produced from methylglyoxal. In glycolysis, one of the intermediates is glycerone phosphate (dihydroxyacetone phosphate). The conversion of it to methylglyoxal, a toxic product can take place either spontaneously or by the action of enzyme methylglyoxal synthase in various organisms. In P. falciparum, there are no genes for methylglyoxal synthase identified and no enzymatic activity was experimentally detected. This suggests that this reaction takes place spontaneously. The genes for glyoxalase-I and glyoxalase-II are present in P. falciparum genome and their activities are also experimentally detected with parasite having 2-3 fold higher specific activities. The presence of different kinetic properties between enzymes from parasite material and from that of erythrocytes was also observed [1]. The genes for glyoxalase I and II were identified in T. gondii genome. It suggests the presence of this pathway and production of D-lactate from methylglyoxal in T. gondii.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Aldehyde reductase 1.1.1.21 TGME49_208040    
Aldehyde reductase 1.1.1.21 TGME49_270100    
Hydroxyacylglutathione hydrolase (Glyoxalase II) 3.1.2.6 TGME49_281630 Mitochondrion Previous publication
Lactoylglutathione lyase (Glyoxalase I) 4.4.1.5 TGME49_248400 Cytoplasm-nuclear Previous publication

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Glycerone-P Glycolysis D-Lactate Host
    Propane-1,2-diol Host
Glutathione Redox metabolism Glutathione Redox metabolism