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 |
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
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