Methionine metabolism

Methionine, an essential amino acid in humans is also essential to all apicomplexans and need to be salvaged from the host. The methionine metabolism pathway in Toxoplasma gondii is essential for providing two important substrates of other pathways. Homocysteine is essential for cysteine biosynthesis from serine (glycine, serine and cysteine metabolism) and S-adenosylmethionine plays an important role as the methyl group donor in various reactions (Examples of adenosylmethionine-dependent methyltransferases in Toxoplasma gondii genome).

 

A metabolic capability that is present in Plasmodium falciparum and absent in T. gondii is the synthesis of polyamines such as spermine and spermidine. This has been incorporated with methionine metabolism in MPMP. In addition to the absence of genes coding for the enzymes ornithine decarboxylase, arginine decarboxylase and spermine/spermidine synthase, the enzymes ornithine decarboxylase and arginine decarboxylase were not experimentally detected. It has been demonstrated that T. gondii can synthesise putrescine from host spermine in a backward reaction. It was also shown that arginine from the host can be metabolised to ornithine and carbamoyl phosphate [1]. Polyamine oxidase and spermidine N-acetyltransferase (SAT), spermine/spermidine N-acetyltransferase (SSAT) enzymes are present in T. gondii and Neospora caninum genomes. Other enzymes biochemically shown to be involved in arginine and spermine metabolism such as arginine deiminase and ornithine carbamoyltransferase are not yet identified in the genome. The enzyme [methionine synthase]-reductase, present in T. gondii genome, is absent in P. falciparum.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
[methionine synthase] reductase 1.16.1.8 TGME49_249320 Nucleus Previous publication
S-adenosyl-methyltransferase 2.1.1.- TGME49_215510    
S-adenosyl-methyltransferase 2.1.1.- TGME49_260160    
S-adenosylmethionine-dependent methyltransferase 2.1.1.- TGME49_260610    
Homocysteine S-methyltransferase 2.1.1.10 TGME49_257750 Nucleus Previous publication
Methionyl-tRNA formyltransferase 2.1.2.9 TGME49_235640    
Methionine adenosyl transferase 2.5.1.6 TGME49_240690    
Adenosylhomocysteinase 3.3.1.1 TGME49_225050 Cytosol Previous publication
Met-tRNA ligase 6.1.1.10 TGME49_289300 Mitochondrion Previous publication
tRNA binding protein none TGME49_223140 Mitochondrion Previous publication

 

  List of genes annotated as tRNA-Met in Toxoplasma gondii genome

 

TGME49_002895 TGME49_012750 TGME49_048915 TGME49_048925
TGME49_057140 TGME49_069820 TGME49_100636 TGME49_100651

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Methionine Host Adenosine Purine metabolism
10-formyl-THF Folate biosynthesis    

 

The examples of reactions which uses S-adenosylmethionine as co-substrate can found in the page: Examples of adenosylmethionine-dependent methyltransferases in Toxoplasma gondii genome