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 and Neospora caninum 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 important role as methyl group donor in various reactions (Examples of adenosylmethionine-dependent methyltransferases in Neospora caninum genome). This metabolic pathway is same in T. gondii and N. caninum.

 

A metabolic capability which is present in Plasmodium falciparum and absent in these Coccidians 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 in T. gondii and N. caninum genomes, the enzymes ornithine decarboxylase and arginine decarboxylase were not experimentally detected in T. gondii. It has been demonstrated that T. gondii can synthesise putrescine from host spermine in backward reaction. It was also shown that arginine from 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 N. 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 either genomes. The enzyme [methionine synthase]-reductase, present in T. gondii and N. caninum genomes is absent in P. falciparum.

 

Enzyme EC Number Gene id
[methionine synthase] reductase 1.16.1.8 NCLIV_065520
S-adenosylmethionine-dependent methyltransferase 2.1.1.- NCLIV_026450
S-adenosylmethionine-dependent methyltransferase 2.1.1.- NCLIV_026840
S-adenosylmethionine-dependent methyltransferase 2.1.1.- NCLIV_052430
Homocysteine S-methyltransferase 2.1.1.10 NCLIV_028500
Methionyl-tRNA formyltransferase 2.1.2.9 NCLIV_047660
Methionine adenosyl transferase 2.5.1.6 NCLIV_016880
Adenosylhomocysteinase 3.3.1.1 NCLIV_047660
Met-tRNA ligase 6.1.1.10 NCLIV_041650
tRNA binding protein none NCLIV_006150
tRNA binding protein none NCLIV_006150

 

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

 

NC_LIV_tRNA_080002 NC_LIV_tRNA_090010 NC_LIV_tRNA_100013 NC_LIV_tRNA_140022
NC_LIV_tRNA_140023 NC_LIV_tRNA_140026    

 

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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 Neospora caninum genome