5,10-Methylenetetrahydrofolate

5,10-Methylenetetrahydrofolate is a donor of single-carbon units. 5,10-Methylenetetrahydrofolate can be made from tetrahydrofolate as follows:

Glycine + Tetrahydrofolate + NAD+ -> 5,10-Methylenetetrahydrofolate + CO 2 + NH 3 + NADH + H+

5-Fluorodeoxyuridine monophosphate (FdUMP) is a molecule that is a mechanism-based inhibitor. Irreversible binding of the substance to thymidylate synthase occurs only in the presence of 5,10-methylenetetrahydrofolate, a cofactor for the reaction catalyzed by thymidylate synthase (Figure 22.18). Crystallographic analysis of thymidylate synthase with dUMP and an analog of 5,10-methylenetetrahydrofolate (that could not be acted on by the enzyme) revealed that thymidylate synthase normally makes a transient covalent bond in the process of catalysis of the reaction. Apparently FdUMP's structure traps the enzyme-substrate covalent bond and prevents it from breaking down.

See also: De Novo Biosynthesis of Purine Nucleotides, DHF, THF, 10-Formyltetrahydrofolate, S-Adenosylmethionine and Biological Methylation, Metabolism of Serine, Glycine, and Threonine, Dihydrofolate Reductase, FdUMP, Vitamin B 12 Coenzymes

INTERNET LINK: One Carbon Pool by Folate