5.10- Methylene tetrahydrofolate synthesis from serine

The donation of the methyl group from N5,N10-methylene tetrahydrofolate leads to the oxidation of the cofactor to dihydrofolate. This points to the importance of dihydrofolate reductase (DHFR) in the functioning of thymidylate synthase. Thus, synthesis of TMP requires a supply of both methyl groups—for example, from serine— and reducing equivalents. 

Cells making DNA must also be able to make deoxythymidine triphosphate (dTTP). The key step in the synthesis of dTTP is the conversion of dUMP to dTMP via thymidylate synthase. The reaction requires a source of N5,Nw-methylene tetrahydrofolate (see Sec. 15.7, Fig. 15-19) to provide the methyl group. In this reaction, the tetrahydrofolate is oxidized to dihydrofolate. Dihydrofolate must be reduced to tetrahydrofolate via the enzyme dihydrofolate reductase so that more Af5,A,l0-methylene tetrahydrofolate can be made from serine in a reaction catalyzed by serine hydroxymethyltransferase. These three reactions, which are essential for the formation of dTMP, are shown below. 

Synthesis of thymidyiate requires uridine nucleotide to be converted to the deoxy form. The substrate for Thymidyiate Synthetase is dUMP, the ] J5 jsjio. methylene-tetrahydrofolate (CH3-THF) is the "methyl" donor. This form of folate derives its carbon from serine ... 

The one-carbon cycle involves generation of one-carbon units by converting tetrahydrofolate to 5,10-methylene-THF from serine. 5,10-Methylene THF is subsequently used for synthesis of thymidine from uracil and purines (DNA synthesis). It is also utilized in regeneration of methionine from homocysteine by donation of the methyl group from 5-methyl THF which is formed by... 

Conversion of serine to glycine. This reaction requires tetrahydrofolate as an acceptor of a methylene group from Ser and utilizes pyridoxal phosphate as a cofactor. It results in the formation of 5,10-CH PteGlu, an essential coenzyme for the synthesis of thymidylate. 

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