Characterization of cobalamin-dependent methionine synthase purified from the human malarial parasite, Plasmodium falciparum.

Methionine synthase, which catalyzes the reaction, 5-methyltetrahydrofolate (5-CH3-H4PteGlu) + homocysteine----methionine + tetrahydrofolate, was detected and partially purified from the human malarial parasite, Plasmodium falciparum (K1 isolate). Partial purification was achieved using high-performance size-exclusion and anion-exchange chromatography. The apparent relative molecular weight of the enzyme was estimated as 105,000 daltons, and the apparent Km for 5-CH3-H4PteGlu was 24.2 microM. The enzyme was dependent on adenosylcobalamin or methylcobalamin but not on cobalamin, cyanocobalamin, or hydroxocobalamin in either the absence or presence of S-adenosylmethionine. Preincubation with nitrous oxide markedly inhibited the enzyme. Methionine synthase in P. falciparum may play a role in the supply of methionine and in folate salvage using exogenous 5-CH3-H4PteGlu for tetrahydrofolate metabolism.