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[Biochemistry](https://durgical.com/en/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.

**EC number**
[2.1.1.13](https://www.enzyme-database.org/query.php?ec=2.1.1.13)

**Genes**
MTR

**Structure (PDB)**
[4CCZ](https://www.rcsb.org/structure/4CCZ)

## 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

- [Nitrous oxide](https://durgical.com/en/pharmacology/nitrous-oxide/)
- [Hydroxocobalamin](https://durgical.com/en/pharmacology/hydroxocobalamin/)

## Pathways

- [Methionine cycle and transsulfuration](https://durgical.com/en/biochemistry/pathways/methionine-cycle-and-transsulfuration/)

## Related conditions

- [Homocystinuria](https://durgical.com/en/conditions/homocystinuria/)
- [Methylmalonic acidaemia](https://durgical.com/en/conditions/methylmalonic-acidaemia/)

## Related

- [Homocysteine](https://durgical.com/en/biochemistry/molecules/homocysteine/)
- [S-adenosylmethionine (SAM)](https://durgical.com/en/biochemistry/molecules/s-adenosylmethionine/)
- [One-carbon metabolism (folate, B12 and SAM)](https://durgical.com/en/biochemistry/topics/one-carbon-metabolism/)
- [Dihydrofolate reductase (DHFR)](https://durgical.com/en/biochemistry/enzymes/dihydrofolate-reductase/)
- [Thymidylate synthase](https://durgical.com/en/biochemistry/enzymes/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [MTR: Methionine synthase (human)](https://www.uniprot.org/uniprotkb/Q99707/entry) (UniProt, 2026); [MTR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mtr/) (MedlinePlus, US National Library of Medicine, 2026); [4CCZ: Crystal structure of human 5-methyltetrahydrofolate-homocysteine methyltransferase, the homocysteine and folate binding domains](https://www.rcsb.org/structure/4CCZ) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/methionine-synthase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/methionine-synthase/