4ccz

Structural highlights

Disease

[METH_HUMAN] Defects in MTR are the cause of methylcobalamin deficiency type G (cblG) [MIM:250940]; also known as homocystinuria-megaloblastic anemia complementation type G. It is an autosomal recessive inherited disease that causes mental retardation, macrocytic anemia, and homocystinuria. Mild deficiency in MS activity could be associated with mild hyperhomocysteinemia, a risk factor for cardiovascular disease and possibly neural tube defects. MS mutations could also be involved in tumorigenesis. Defects in MTR may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD) [MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTR may affect the risk of spina bifida via the maternal rather than the embryonic genotype.^{[1] [2]}

Function

[METH_HUMAN] Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

References

1. ↑ Doolin MT, Barbaux S, McDonnell M, Hoess K, Whitehead AS, Mitchell LE. Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida. Am J Hum Genet. 2002 Nov;71(5):1222-6. Epub 2002 Oct 9. PMID:12375236 doi:S0002-9297(07)60417-0
2. ↑ O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Mol Genet Metab. 2005 Jul;85(3):220-7. Epub 2005 Mar 17. PMID:15979034 doi:S1096-7192(05)00052-1