5-Methyltetrahydrofolate-homocysteine methyltransferase Information & 5-Methyltetrahydrofolate-homocysteine methyltransferase Links at HealthHaven.com

5-methyltetrahydrofolate-homocysteine methyltransferase
	PDB rendering based on 2o2k.
Available structures
	2o2k
Identifiers
Symbols	MTR; FLJ45386
External IDs	OMIM: 156570 MGI: 894292 HomoloGene: 37280
EC number	2.1.1.13
Gene ontology
Molecular function	• dihydropteroate synthase activity; • methyltransferase activity; • zinc ion binding; • methionine synthase activity; • homocysteine S-methyltransferase activity; • transferase activity; • cobalamin binding; • metal ion binding; • cobalt ion binding;
Cellular component	• intracellular;
Biological process	• central nervous system development; • amino acid biosynthetic process; • methionine biosynthetic process; • folic acid and derivative biosynthetic process;
RNA expression pattern
	More reference expression data
Orthologs
NP_000245 (protein)	XP_138431 (protein)

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5-Methyltetrahydrofolate-homocysteine methyltransferase (MTR, MTRR) or methionine synthase (MS, MeSe, MetH), is a human gene which codes for an enzyme of the same name.^[1] The enzyme is responsible for the production of methionine from homocysteine. MTR forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle.^[2]

[edit] Function

MTR encodes the enzyme 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme catalyzes the final step in methionine biosynthesis.^[1] Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G, or methylcobalamin deficiency cbl G type.^[1]

MTR 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 MTR reaction (click to enlarge)

MTR is the only mammalian enzyme that metabolizes 5-mTHF to regenerate the active cofactor, THF. Deficiency in MTR 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 MTR).

The consequence of reduced MTR activity is megaloblastic anemia.

[edit] Genetics

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

2756A→G (Asp⁹¹⁹Gly)

[edit] See also

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

[edit] References

^ ^a ^b ^c "MTR 5-methyltetrahydrofolate-homocysteine methyltransferase (Homo sapiens)". Entrez. 19 May 2009. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4548. Retrieved 24 May 2009.
^ Banerjee RV, Matthews RG (1990). "Cobalamin-dependent methionine synthase". Faseb J. 4 (5): 1450–9. PMID 2407589. http://www.fasebj.org/cgi/reprint/4/5/1450.pdf.

[edit] Further reading

Banerjee RV, Matthews RG (1990). "Cobalamin-dependent methionine synthase.". Faseb J. 4 (5): 1450–9. PMID 2407589.
Ludwig ML, Matthews RG (1997). "Structure-based perspectives on B12-dependent enzymes.". Annu. Rev. Biochem. 66: 269–313. doi:10.1146/annurev.biochem.66.1.269. PMID 9242908.
Matthews RG, Sheppard C, Goulding C (1998). "Methylenetetrahydrofolate reductase and methionine synthase: biochemistry and molecular biology.". Eur. J. Pediatr. 157 Suppl 2: S54–9. doi:10.1007/PL00014305. PMID 9587027.
Garovic-Kocic V, Rosenblatt DS (1992). "Methionine auxotrophy in inborn errors of cobalamin metabolism.". Clinical and investigative medicine. Médecine clinique et experimentale 15 (4): 395–400. PMID 1516297.
O'Connor DL, Moriarty P, Picciano MF (1992). "The impact of iron deficiency on the flux of folates within the mammary gland.". International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition 62 (2): 173–80. PMID 1517041.
Everman BW, Koblin DD (1992). "Aging, chronic administration of ethanol, and acute exposure to nitrous oxide: effects on vitamin B12 and folate status in rats.". Mech. Ageing Dev. 62 (3): 229–43. doi:10.1016/0047-6374(92)90109-Q. PMID 1583909.
Vassiliadis A, Rosenblatt DS, Cooper BA, Bergeron JJ (1991). "Lysosomal cobalamin accumulation in fibroblasts from a patient with an inborn error of cobalamin metabolism (cblF complementation group): visualization by electron microscope radioautography.". Exp. Cell Res. 195 (2): 295–302. doi:10.1016/0014-4827(91)90376-6. PMID 2070814.
Li YN, Gulati S, Baker PJ, et al. (1997). "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.
Gulati S, Baker P, Li YN, et al. (1997). "Defects in human methionine synthase in cblG patients.". Hum. Mol. Genet. 5 (12): 1859–65. doi:10.1093/hmg/5.12.1859. PMID 8968736.
Leclerc D, Campeau E, Goyette P, et al. (1997). "Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.". Hum. Mol. Genet. 5 (12): 1867–74. doi:10.1093/hmg/5.12.1867. PMID 8968737.
Chen LH, Liu ML, Hwang HY, et al. (1997). "Human methionine synthase. cDNA cloning, gene localization, and expression.". J. Biol. Chem. 272 (6): 3628–34. doi:10.1074/jbc.272.6.3628. PMID 9013615.
Wilson A, Leclerc D, Saberi F, et al. (1998). "Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.". Am. J. Hum. Genet. 63 (2): 409–14. doi:10.1086/301976. PMID 9683607.
Salomon O, Rosenberg N, Zivelin A, et al. (2002). "Methionine synthase A2756G and methylenetetrahydrofolate reductase A1298C polymorphisms are not risk factors for idiopathic venous thromboembolism.". Hematol. J. 2 (1): 38–41. doi:10.1038/sj/thj/6200078. PMID 11920232.
Watkins D, Ru M, Hwang HY, et al. (2002). "Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.". Am. J. Hum. Genet. 71 (1): 143–53. doi:10.1086/341354. PMID 12068375.
De Marco P, Calevo MG, Moroni A, et al. (2002). "Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population.". J. Hum. Genet. 47 (6): 319–24. doi:10.1007/s100380200043. PMID 12111380.
Doolin MT, Barbaux S, McDonnell M, et al. (2003). "Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.". Am. J. Hum. Genet. 71 (5): 1222–6. doi:10.1086/344209. PMID 12375236.
Zhu H, Wicker NJ, Shaw GM, et al. (2004). "Homocysteine remethylation enzyme polymorphisms and increased risks for neural tube defects.". Mol. Genet. Metab. 78 (3): 216–21. doi:10.1016/S1096-7192(03)00008-8. PMID 12649067.

[edit] External links

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[entrez-0] "MTR 5-methyltetrahydrofolate-homocysteine methyltransferase (Homo sapiens)". Entrez. 19 May 2009. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4548. Retrieved 24 May 2009.

[1] Banerjee RV, Matthews RG (1990). "Cobalamin-dependent methionine synthase". Faseb J. 4 (5): 1450–9. PMID 2407589. http://www.fasebj.org/cgi/reprint/4/5/1450.pdf.

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