Methionine synthase

5-methyltetrahydrofolate-homocysteine methyltransferase
PDB rendering based on 2o2k.
Available structures PDB 2o2k
Identifiers
Symbols	MTR; FLJ33168; FLJ43216; FLJ45386; MS; cblG
External IDs	OMIM: 156570 MGI: 894292 HomoloGene: 37280 GeneCards: MTR Gene
EC number	2.1.1.13
Gene Ontology Molecular function • protein binding • folic acid binding • methyltransferase activity • zinc ion binding • methionine synthase activity • homocysteine S-methyltransferase activity • transferase activity • cobalamin binding • metal ion binding Cellular component • intracellular • soluble fraction • cytoplasm • cytosol Biological process • protein methylation • xenobiotic metabolic process • nervous system development • cellular amino acid biosynthetic process • methionine biosynthetic process • methylation • pteridine-containing compound metabolic process • tetrahydrofolate metabolic process • homocysteine metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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]

Function

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, or levomefolic acid) 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.

Genetics

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

• 2756A→G (Asp⁹¹⁹Gly)

See also

• Methyltransferase
• Arakawa's syndrome II
• 5-Methyltetrahydrofolate (5-Me-THF, 5-Me-H₄F)

References

Further reading

External links

• GeneReviews/NCBI/NIH/UW entry on Disorders of Intracellular Cobalamin Metabolism
• ENZYME: EC 2.1.1.13
• MeSH 5-Methyltetrahydrofolate-Homocysteine+S-Methyltransferase

v · d · ePDB gallery 2o2k: Crystal Structure of the Activation Domain of Human Methionine Synthase Isoform/Mutant D963E/K1071N