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 significan t activity of methylenetetrahydrofolate reductase (MTHFR). The presenc e of this enzyme completes the methionine synthesis cycle, in which th e one-carbon fragment from serine side-chain can be transferred to met hionine. However, while metabolic labelling of methionine from L-3 [C- 14]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 co factor was incorporated into methionine, and the folate cofactor was f ound in the same pool as that derived from de novo synthesis with p-am inobenzoic 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 mor e stable precursors salvaged by the parasites.