5,10-Methylenetetrahydrofolate


5,10-Methylenetetrahydrofolate is cofactor in several biochemical reactions. It exists in nature as the diastereoisomer -5,10-methylene-THF.
As an intermediate in one-carbon metabolism, 5,10-CH2-THF converts to 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and methenyltetrahydrofolate. It is substrate for the enzyme methylenetetrahydrofolate reductase, which gives 5-methyltetrahydrofolate. It is mainly produced by the reaction of tetrahydrofolate with serine, catalyzed by the enzyme serine hydroxymethyltransferase.

Selected functions

Formaldehyde equivalent

Methylenetetrahydrofolate is a source of the equivalent of formaldehyde or CH22+ in biosyntheses.
Methylenetetrahydrofolate is also an intermediate in the detoxification of formaldehyde.

Pyrimidine biosynthesis

It is the one-carbon donor for thymidylate synthase, for methylation of 2-deoxy-uridine-5-monophosphate to 2-deoxy-thymidine-5-monophosphate. The coenzyme is necessary for the biosynthesis of thymidine and is the C1-donor in the reactions catalyzed by TS and thymidylate synthase (FAD).

Biomodulator

-5,10-methylene-THF is a biomodulator that has proven to enhance the desired cytotoxic antitumor effect of Fluorouracil and can bypass the metabolic pathway required by other folates to achieve necessary activation. The active metabolite is being evaluated in clinical trials for patients with colorectal cancer in combination with 5-FU.