The methionine synthesis cycle and salvage of methyltetrahydrofolate from host red cells in the malaria parasite (Plasmodium falciparum).
Plasmodium falciparum, P. knowlesi and P. chabaudi showed a significant activity of methylenetetrahydrofolate reductase (MTHFR). The presence of this enzyme completes the methionine synthesis cycle, in which the one-carbon fragment from serine side-chain can be transferred to methionine. However, while metabolic labelling of methionine from L-3 [14C]serine could not be demonstrated in P. falciparum, the significance of MTHFR was implicated by a novel pathway for salvage of exogenous 5-methyltetrahydrofolate from the host cell. The methyl group of the cofactor was incorporated into methionine, and the folate cofactor was found in the same pool as that derived from de novo synthesis with p-aminobenzoic acid as the precursor, shown previously as polyglutamylated 5-methyltetrahydrofolate. It is proposed from these results that the function of MTHFR and the methionine synthesis cycle is not the supply of methionine, but the generation of active folate cofactors from more stable precursors salvaged by the parasites.
Asawamahasakda
W
W
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Yuthavong
Y
Y
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000096:biosynthesis*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008954:Models, Biological; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000032:analysis; D016788:Plasmodium chabaudi / Q000201:enzymology; D010963:Plasmodium falciparum / Q000201:enzymology / Q000378:metabolism*; D016790:Plasmodium knowlesi / Q000201:enzymology; D012694:Serine / Q000378:metabolism; D013763:Tetrahydrofolates / Q000096:biosynthesis* / Q000378:metabolism*
D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D012694:Serine; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate