Uptake of folate and its analogue-amethopterin by mouse L-cells.

1. The uptake of folate and amethopterin by the mouse transformed L-cells was found to depend on their extracellular concentration and time of incubation. The uptake conforms to Michaelis-Menten kinetics (Km values 10(-4) M and 10(-6) M for folate and amethopterin, respectively) and is temperature-dependent. 2. The observed differential effect of actinomycin D, cycloheximide and pCMB on the uptake of folate and amethopterin and lack of a pronounced transinhibition in the transport of these compounds indicate the existence in L-cells of two separate transport systems for folate and its analogue. 3. Methionine added to the culture medium enhances the uptake of folate, but not that of amethopterin. 4. Under conditions of methionine-dependent increase of folate uptake the activity of dihydrofolate reductase remains unaltered while that of methionine synthetase is markedly reduced. 5. The efficiency of folate uptake seems to be related rather to the modulations of methionine synthetase activity than to changes in the activity of dihydrofolate reductase.