Methylation: methionine and homocysteine: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Homocysteine, methionine, MTHFR genetics: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Methionine and homocysteine are sulphur-containing amino acids in a cycle that supplies methyl groups. Methionine forms SAM, which donates methyl groups to DNA, proteins and messengers; with folate and vitamin B12, homocysteine is turned back into methionine.

The pathway step by step

1. Methionine → SAM MAT · ATP, Magnesium The enzyme MAT joins methionine with ATP to form S-adenosylmethionine. SAM is the compound from which the cell draws methyl groups – small carbon building blocks. Source 7, 1
2. SAM → SAH Methyltransferases Methyltransferases transfer the methyl group from SAM to DNA, proteins and messengers. What remains is S-adenosylhomocysteine. Source 1, 3
3. 5,10-Methylene-THF → 5-Methyl-THF MTHFR · Vitamin B2 (FAD), NADPH MTHFR converts 5,10-methylene-THF into 5-methyl-THF. The common gene variant C677T results in a less stable enzyme that works more slowly. Source 4, 2
4. Homocysteine → Methionine renewed Methionine synthase · Vitamin B12 Methionine synthase transfers the methyl group from 5-methyl-THF to homocysteine. Vitamin B12 is the cofactor here; this closes the cycle. Source 2
5. Homocysteine → Cystathionine CBS · Vitamin B6 (PLP), Serine The second route is called transsulphuration. Cystathionine β-synthase joins homocysteine with serine; it works with pyridoxal phosphate, the active form of vitamin B6. Source 5
6. Cystathionine → Cysteine Cystathionine γ-lyase · Vitamin B6 (PLP) Cystathionine γ-lyase splits cystathionine, producing cysteine. This enzyme also uses pyridoxal phosphate. Source 5
7. Cysteine → Glutathione GCL and GS · Glutamate, glycine, ATP Two enzymes link cysteine with glutamate and glycine to form glutathione, the most abundant sulphur-containing molecule in the cell. Each step uses ATP. Source 6

Cofactors in this pathway

• Folate — As 5-methyl-THF, supplies the methyl group that turns homocysteine into methionine Source 2, 3In the ORY catalogue as a laboratory value: Folsäure
• Vitamin B12 — Cofactor of methionine synthase, which transfers the methyl group from folate to homocysteine Source 2In the ORY catalogue as a laboratory value: Vitamin B12
• Vitamin B6 — As pyridoxal phosphate, cofactor of CBS and cystathionine gamma-lyase Source 5In the ORY catalogue as a laboratory value: Vitamin B6
• Vitamin B2 (FAD) — As FAD, cofactor of MTHFR, which forms 5-methyl-THF Source 4
• Magnesium — Accompanies ATP in MAT, which converts methionine to SAM Source 7In the ORY catalogue as a laboratory value: Magnesium
• Serine — Joined with homocysteine by CBS to form cystathionine Source 5In the ORY catalogue as a laboratory value: Serin
• Glycine — Building block of glutathione, together with cysteine and glutamate Source 6In the ORY catalogue as a laboratory value: Glycin
• Betaine — Methyl group donor for BHMT, a second route back to methionine in the liver Source 1

Sources

1. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999 · PubMed 10448523
2. Froese DS, Fowler B et al. Vitamin B12, folate, and the methionine remethylation cycle — biochemistry, pathways, and regulation. J Inherit Metab Dis 2019 · PubMed 30693532
3. Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Cell Metab 2017 · PubMed 27641100
4. Blomgren LKM, Guo S, Froese DS. 5,10-Methylenetetrahydrofolate Reductase — the Key Allosteric Regulator in One-Carbon Metabolism. Biochemistry 2026 · PubMed 41758688
5. Sbodio JI, Snyder SH, Paul BD. Regulators of the transsulfuration pathway. Br J Pharmacol 2019 · PubMed 30007014
6. Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013 · PubMed 22995213
7. Lu SC. S-Adenosylmethionine. Int J Biochem Cell Biol 2000 · PubMed 10762064

Related pathways

• Glutathione — homocysteine
• Vitamin B12 — methionine
• Taurine — methionine
• Vitamin B6 — homocysteine
• Folic acid — 5,10-methylene-thf

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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