Four steps from homoserine. The sulfur comes from cysteine and the methyl group from a folate
Route: Homoserine + Suc-CoA → O-Succinylhomoserine + Cysteine → Cystathionine → Homocysteine → Methionine
Methionine is an essential amino acid, so humans must eat it. This is the route in E. coli. Homoserine is activated with a succinyl group from succinyl-CoA. Cystathionine γ-synthase, which needs pyridoxal phosphate, replaces the succinate with the sulfur of cysteine and makes cystathionine. Cystathionine β-lyase, also a pyridoxal phosphate enzyme, cuts the other side of the sulfur atom and releases pyruvate and ammonium, which leaves homocysteine. The last step moves a methyl group from 5-methyltetrahydrofolate onto the sulfur. The enzyme shown is the version that carries the methyl group on vitamin B12 (cobalamin) as an intermediate. Many organisms also have a second methionine synthase that needs no B12. Other organisms activate homoserine differently: yeast uses an acetyl group instead of a succinyl group, and the plant Arabidopsis uses the phosphate made in the threonine pathway. Humans can turn dietary methionine into homocysteine and cysteine, but they cannot make the carbon skeleton.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Homoserine O-succinyltransferase | 2.3.1.46 | CoA-SH | |
| 2 | Cystathionine γ-synthase | 2.5.1.48 | Succinate | |
| 3 | Cystathionine β-lyase | 4.4.1.13 | H₂O | Pyruvate, NH₄⁺ |
| 4 | Methionine synthase | 2.1.1.13 | 5-CH₃-THF | THF |
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).