Comparative Biological Activity of Leucovorin and Pteroylglutamic Acid

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Abstract
The biological properties of leucovorin, a synthetic substance derived from pteroylglutamic acid (PGA) and having the biological properties of the citrovorum factors were compared with those of PGA. Leucovorin in the amount of 0.15 mμg per milliliter of culture medium was required for half-maximum growth of Leuconostoc citrovorum, but 200,000 times as much PGA was required to elicit the same growth response. About twice as much leucovorin as PGA was needed for growth of Streptococcus faecalis, Lactobacillus casei, and chicks. Leucovorin was also effective in meeting the requirement of turkeys for folic acid. Leucovorin was more effective for chicks and turkeys when given by injection than when fed in the diet. About 8 times as much 4-aminopteroylglutamic acid (aminopterin) was required to reduce the growth of S. faecalis to half maximum in the presence of leucovorin as was required in the presence of an equimolar amount of PGA. With mice, approximately an equal amount of leucovorin was required to reverse the toxicity of aminopterin when the two substances were injected simultaneously. If the aminopterin dose preceded the leucovorin dose by one to two hours, the toxic effects could be reversed only by the injection of a much larger amount of leucovorin.