methionine synthase; 5-methyltetrahydrofolate:homocysteine methyltransferase; vitamin-B12 dependent methionine synthase; tetrahydropteroyl-glutamate methyltransferase; MS (MTR)
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Function
- one of 2 vitamin B12-dependent enzymes in mammals
- catalyzes methylcobalamin-dependent transfer of methyl group from N5-methyl tetrahydrofolate to homocysteine to form methionine & tetrahydrofolate.
- in connection with 5,10-methylenetetrahydrofolate reductase activity which generates N5-methyltetrahydrofolate, methionine synthase regulates methionine synthesis & tetrahydrofolate generation
- availability of tetrahydrofolate is critical to DNA generation
- amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine
5-methyltetrahydrofolate + L-homocysteine
<-->
tetrahydrofolate + L-methionine
Cofactor: methylcobalamin (MeCBL)
Structure
- modular enzyme with four functionally distinct domains
- the isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine
- the Hcy-binding domain in association with the pterin-binding domain catalyzes methylation of cobalamin by methyltetrahydrofolate & the methylation of homocysteine
- the B12-binding domain binds the cofactor
- binds 1 Zn+2 per subunit (putative)
- L-homocysteine is bound via Zn+2
- the AdoMet activation domain binds S-adenosyl-L-methionine
- under aerobic conditions cobalamin [Co+] can be converted to inactive cobalamin [Co+2]
- reductive methylation by S-adenosyl-L-methionine & flavodoxin regenerates methylcobalamin
- belongs to the vitamin-B12 dependent methionine synthase family
- contains 1 AdoMet activation domain
- contains 1 B12-binding domain
- contains 1 B12-binding N-terminal domain
- contains 1 Hcy-binding domain
- contains 1 pterin-binding domain
Compartment
Expression
- widely expressed
- expressed at the highest levels in pancreas, heart, brain, skeletal muscle & placenta
- expressed at lower levels in lung, liver & kidney
Pathology
- defects in MTR are the cause of
- methylcobalamin deficiency type G
- susceptibility to folate-sensitive neural tube defects
- hyperhomocysteinemia
- may paly role in tumorigenesis
More general terms
Additional terms
- 5,10-methylenetetrahydrofolate reductase (MTHFR)
- folate metabolism
- homocysteine
- methionine
- methionine metabolism (trans-sulfuration pathway)
- methylcobalamin (vitamin B12)
- N5-methyltetrahydrofolate
- tetrahydrofolate (THF)
References
- ↑ Stryer Biochemistry WH Freeman & Co, New York, 1988 pg 508, 583
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2200
- ↑ UniProt http://www.uniprot.org/uniprot/Q99707.html
- ↑ Wikipedia; 5-methyltetrahydrofolate-homocysteine methyltransferase entry http://en.wikipedia.org/wiki/5-methyltetrahydrofolate-homocysteine_methyltransferase
Database
- UniProt: http://www.uniprot.org/uniprot/Q99707.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4548
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4548
- OMIM: https://mirror.omim.org/entry/156570
- OMIM: https://mirror.omim.org/entry/250940
- OMIM: https://mirror.omim.org/entry/601634
- OMIM: https://mirror.omim.org/entry/603174