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 |
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
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