5-methyltetrahydrofolate-homocysteine methyltransferase

5-methyltetrahydrofolate-homocysteine methyltransferase
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "5-methyltetrahydrofolate-homocysteine_methyltransferase".

content

5-methyltetrahydrofolate-homocysteine methyltransferase

PDB rendering based on 2o2k.

Available structures: 2o2k

Identifiers

MTR; FLJ45386

External IDs

OMIM: 156570 MGI: 894292 HomoloGene: 37280

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

Human

Mouse

ENSG00000116984

ENSMUSG00000021311

n/a

Refseq

NM_000254 (mRNA)
NP_000245 (protein)

XM_138431 (mRNA)
XP_138431 (protein)

Location

Chr 1: 235.03 - 235.13 Mb

Chr 13: 12.27 - 12.31 Mb

Pubmed search

5-methyltetrahydrofolate-homocysteine methyltransferase, also known as MTR, is a human gene.^[1]

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

5-Methyltetrahydrofolate-homocysteine methyltransferase or (MTR) is an enzyme responsible for the production of methionine from homocysteine. MTR forms part of the S-adenosyl methionine cycle and is also called methionine synthase.^[2]

Contents

1 Function
2 Genetics
3 See also
4 References
5 Further reading
6 External links

Function

MTR contains the cofactor - methylcobalamin (MeB₁₂) and uses the substrates N5-methyl-tetrahydrofolate (N⁵-methyl-THF) 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

The MTR reaction

MTR is the only mammalian enzyme that metabolizes 5-methylTHF to regenerate the active cofactor, tetrahydrofolate. 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.

Genetics

Several polymorphisms in MTR have been identified. 2756A->G (Asp⁹¹⁹Gly)

See also

References

^ ^a ^b "Entrez Gene: MTR 5-methyltetrahydrofolate-homocysteine methyltransferase".
^ Banerjee RV, Matthews RG (1990). "Cobalamin-dependent methionine synthase". FASEB J. 4 (5): 1450–9. PMID 2407589.

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. PMID 12649067.

External links

This transferase article is a stub. You can help Wikipedia by expanding it.

v • d • e Transferase: one carbon transferases (EC 2.1)

2.1.1 - Methyltransferases	N-methyltransferase: Histamine N-methyltransferase - Phenylethanolamine N-methyltransferase - Tryptamine N-methyltransferase - Phosphatidylethanolamine N-methyltransferase O-methyltransferase: 5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase - Catechol-O-methyl transferase homocysteine methyltransferase: Betaine-homocysteine methyltransferase - Homocysteine methyltransferase - 5-Methyltetrahydrofolate-homocysteine methyltransferase Other: Phosphatidyl ethanolamine methyltransferase - DNMT3B - Histone methyltransferase - Thymidylate synthase - DNA methyltransferase

2.1.2 - Hydroxy methyl-, Formyl- and Related Transferases	Serine hydroxymethyltransferase - Phosphoribosylglycinamide formyltransferase - Inosine monophosphate synthase - Glutamate formimidoyltransferase - Aminomethyltransferase

2.1.3 - Carboxy- and Carbamoyl transferases	Ornithine transcarbamylase

2.1.4 - Amidino transferases	Arginine:glycine amidinotransferase

v • d • e

Metabolism: amino acid metabolism - synthesis and catabolism enzymes (essential in CAPS)

glycine→serine→	Serine hydroxymethyltransferase - Serine dehydratase

alanine→	Alanine transaminase

cysteine→	D-cysteine desulfhydrase

threonine→	L-threonine dehydrogenase


HISTIDINE→	Histidine ammonia-lyase - Urocanate hydratase - Formiminotransferase cyclodeaminase

proline→	Proline oxidase - Pyrroline-5-carboxylate reductase - 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 - PYCR1

arginine→	Ornithine aminotransferase - Ornithine decarboxylase - Agmatinase

→alpha-ketoglutarate→TCA	Glutamate dehydrogenase

G→propionyl-CoA


PHENYLALANINE→tyrosine→	Phenylalanine hydroxylase - Tyrosine aminotransferase - 4-Hydroxyphenylpyruvate dioxygenase - Homogentisate 1,2-dioxygenase - Fumarylacetoacetate hydrolase

G→oxaloacetate


asparagine→aspartate→	Asparaginase/Asparagine synthetase - Aspartate transaminase

Other

see also disorders, intermediates

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