Biochemistry · Enzyme
Methionine synthase !
Methionine synthase moves a methyl from 5-methyltetrahydrofolate to homocysteine. It links the folate cycle with vitamin B12.
Updated 2026-11-01
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Key facts
- 5-methyl-THF + homocysteine → THF + methionine; it uses methylcobalamin (B12).
- It is the only reaction that recovers THF from 5-methyl-THF.
- It is one of the two human enzymes that need B12; the other is methylmalonyl-CoA mutase.
- Methionine synthase reductase (MTRR) reactivates oxidised cobalamin using SAM.
Structure
- 4CCZ: the human homocysteine- and folate-binding domains with tetrahydrofolate bound.
Regulation
- Its reactivation needs the reductase MTRR and SAM.
Inhibitors and toxins
- Nitrous oxide: oxidises cobalamin and switches the enzyme off.
Clinical notes
- Without B12, folate is trapped as 5-methyl-THF (methyl-folate trap) and megaloblastic anaemia appears.
- Nitrous oxide can trigger neurological damage in people low in B12.
- Variants of MTR or MTRR cause homocystinuria with low methionine.
Drugs that act here
Pathways
Related conditions
Related
- Homocysteine
- S-adenosylmethionine (SAM)
- One-carbon metabolism (folate, B12 and SAM)
- Dihydrofolate reductase (DHFR)
- Thymidylate synthase
Test yourself
Think of the answer, then tap the question to see it.
What is the methyl-folate trap?
Without B12 methionine synthase stops and folate is stuck as 5-methyl-THF, which cannot be used to make DNA.
Which two human enzymes need vitamin B12?
Methionine synthase and methylmalonyl-CoA mutase.
Why is nitrous oxide risky with B12 deficiency?
It oxidises the cobalamin of methionine synthase and inactivates it, worsening the functional deficiency.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: MTR: Methionine synthase (human) (UniProt, 2026); MTR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 4CCZ: Crystal structure of human 5-methyltetrahydrofolate-homocysteine methyltransferase, the homocysteine and folate binding domains (RCSB Protein Data Bank, 2026).
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