Serine gives up its side-chain carbon to tetrahydrofolate, which is then reduced to the methyl form that makes methionine
Route: Serine → 5,10-CH₂-THF → 5-CH₃-THF + Homocysteine → THF + Methionine
Tetrahydrofolate (THF) carries one-carbon units on its nitrogen atoms. Serine hydroxymethyltransferase, which needs pyridoxal phosphate, takes the side-chain carbon of serine and leaves glycine behind. The carbon sits on THF as a methylene bridge between two nitrogens (5,10-methylene-THF). That form supplies the methyl group of thymidylate. Methylenetetrahydrofolate reductase uses NADPH to reduce the bridge to a methyl group on N5. Methionine synthase then hands the methyl group to homocysteine and gives back THF, so the cycle is closed. The route follows the carbon from serine to methionine; other folate forms, such as 10-formyl-THF, are used in the purine pathway. The drawings show folate with one glutamate; in cells folate carries a longer polyglutamate chain.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Serine hydroxymethyltransferase | 2.1.2.1 | THF | Glycine, H₂O |
| 2 | Methylenetetrahydrofolate reductase | 1.5.1.53 | NADPH | NADP⁺ |
| 3 | Methionine synthase | 2.1.1.13 |
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).