Methionine synthase

Methionine synthase
5-methyltetrahydrofolate-homocysteine methyltransferase

PDB rendering based on 2o2k.
Symbols MTR; FLJ33168; FLJ43216; FLJ45386; MS; cblG
External IDs OMIM156570 MGI894292 HomoloGene37280 GeneCards: MTR Gene
EC number
RNA expression pattern
PBB GE MTR 203774 at tn.png
More reference expression data
Species Human Mouse
Entrez 4548 238505
Ensembl ENSG00000116984 ENSMUSG00000021311
UniProt Q99707 n/a
RefSeq (mRNA) NM_000254.2 NM_001081128.2
RefSeq (protein) NP_000245.2 NP_001074597.1
Location (UCSC) Chr 1:
236.96 – 237.07 Mb
Chr 13:
12.28 – 12.35 Mb
PubMed search [1] [2]

Methionine synthase also known as MS, MeSe, MetH is an enzyme that in humans is encoded by the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase).[1][2] This enzyme is responsible for the regeneration of methionine from homocysteine. Methionine synthase forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle.[3]



Methionine synthase is enzyme 4

Methionine synthase catalyzes the final step in the regeneration of methionine from homocysteine.

Methionine synthase contains the cofactor methylcobalamin (MeB12) and uses the substrates N5-methyl-tetrahydrofolate (N5-mTHF) and homocysteine.

The enzyme works in two steps in a ping-pong reaction. First, methylcobalamin is formed by a methyl group transfer from N5-mTHF with formation of MeB12 and tetrahydrofolate (THF). In the second step, MeB12 transfers this methyl group to homocysteine, regenerating the cofactor cobalamin and releasing the product methionine.

The reaction reaction catalyzed by methionine synthase (click to enlarge)

Methionine synthase is the only mammalian enzyme that metabolizes 5-mTHF to regenerate the active cofactor THF. Deficiency in methionine synthase function may be due to genetic mutations, reduced levels of its cobalamin cofactor (vitamin B12), or decreased levels of the enzyme (methionine synthase) reductase (required for the sustained activity of methionine synthase).

Clinical significance

Mutations in the MTR gene have been identified as the underlying cause of methylcobalamin deficiency complementation group G, or methylcobalamin deficiency cblG-type.[1] The consequence of reduced methionine synthase activity is megaloblastic anemia.


Several polymorphisms in the MTR gene have been identified.[citation needed]

  • 2756A→G (Asp919Gly)

See also


  1. ^ a b "MTR 5-methyltetrahydrofolate-homocysteine methyltransferase (Homo sapiens)". Entrez. 19 May 2009. Retrieved 24 May 2009. 
  2. ^ Li YN, Gulati S, Baker PJ, Brody LC, Banerjee R, Kruger WD (December 1996). "Cloning, mapping and RNA analysis of the human methionine synthase gene". Hum. Mol. Genet. 5 (12): 1851–8. doi:10.1093/hmg/5.12.1851. PMID 8968735. 
  3. ^ Banerjee RV, Matthews RG (March 1990). "Cobalamin-dependent methionine synthase". FASEB J. 4 (5): 1450–9. PMID 2407589. 

Further reading

External links