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Gene Review

MTRR  -  5-methyltetrahydrofolate-homocysteine...

Homo sapiens

Synonyms: MSR, Methionine synthase reductase, cblE
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Disease relevance of MTRR


Psychiatry related information on MTRR

  • Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85) [6].
  • We did not find significant interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary folate and alcohol consumption [7].
  • Therefore expressing intensity as a percentage of MSR for sub-maximal and maximal velocities and as a percentage of AnSR for supra-maximal velocities allows individual differences in anaerobic work capacity to be taken into account and running times to exhaustion to be predicted accurately [8].
  • Eight HIV-1-infected methadone patients with impaired neuropsychological test performance participated in an inpatient double-blind placebo-controlled crossover trial of MSR 20-40 mg/day [9].

High impact information on MTRR

  • Escherichia coli MS, however, was not activated by hMSR [10].
  • Apoenzyme alone is quite unstable at 37 degrees C. MSR also is able to reduce aquacobalamin to cob(II)alamin in the presence of NADPH, and this reduction leads to stimulation of the conversion of apoMS and aquacobalamin to MS holoenzyme [10].
  • Analysis of data on variants of two genes involved in homocysteine remethylation/methionine biosynthesis--methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G--provided evidence that both variants influence the risk of spina bifida via the maternal rather than the embryonic genotype [11].
  • In the present report, we asked whether variation at MTHFR (677C-->T) or MTRR (66A-->G) might be associated with human trisomies other than trisomy 21 [12].
  • Methionine synthase reductase (MTRR) is another enzyme essential for normal folate metabolism [13].

Chemical compound and disease context of MTRR


Biological context of MTRR

  • The prevalence of the MTRR AA, AG, GG genotypes was 19, 50 and 31%, respectively [15].
  • Recent evidence has suggested that 5,10-methylenetetrahydrofolate reductase (MTHFR) and/or methionine synthase reductase (MTRR) might contribute to the maternal risk of trisomy 21 [16].
  • The gene MTRR has been localized to chromosome 5p15.2-15 [17].
  • Therefore, studies on human genotoxicity based on cytogenetic markers of MN should take into account both the MTRR polymorphism and the potential confounding effect of smoking, although these preliminary findings need to be validated in larger populations because of the relatively small sample size [18].
  • The insertion is caused by a T>C transition within intron 6 of the MTRR gene, which presumably leads to activation of an exon splicing enhancer [19].

Anatomical context of MTRR


Associations of MTRR with chemical compounds


Physical interactions of MTRR

  • Electron transfer from MSR to the cob(II)alamin cofactor coupled with methyl transfer from S-adenosyl methionine returns MS to the active methylcob(III)alamin state [26].

Enzymatic interactions of MTRR


Other interactions of MTRR

  • Patients with the MTHFR 1298AC variant or the MTRR 66 G-allele showed decreased in vitro MTX sensitivity measured under both test conditions [23].
  • Moreover, after correction for age, gender and GSTM1 genotype, a significant association (P = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed [4].
  • Investigations also showed that purified recombinant human methionine synthase reductase (MSR) in combination with purified ATR can convert cob(II)alamin to AdoCbl in vitro [28].
  • Four genetic polymorphisms-MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys-were determined using blood samples [29].
  • Our preliminary findings suggest no association between the MTRR A66G and MTHFR A1298C polymorphisms and MS [30].

Analytical, diagnostic and therapeutic context of MTRR


  1. Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans. Guéant-Rodriguez, R.M., Rendeli, C., Namour, B., Venuti, L., Romano, A., Anello, G., Bosco, P., Debard, R., Gérard, P., Viola, M., Salvaggio, E., Guéant, J.L. Neurosci. Lett. (2003) [Pubmed]
  2. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. O'Leary, V.B., Mills, J.L., Pangilinan, F., Kirke, P.N., Cox, C., Conley, M., Weiler, A., Peng, K., Shane, B., Scott, J.M., Parle-McDermott, A., Molloy, A.M., Brody, L.C. Mol. Genet. Metab. (2005) [Pubmed]
  3. Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer: a case-control analysis. Shi, Q., Zhang, Z., Li, G., Pillow, P.C., Hernandez, L.M., Spitz, M.R., Wei, Q. Pharmacogenet. Genomics (2005) [Pubmed]
  4. Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects. Zijno, A., Andreoli, C., Leopardi, P., Marcon, F., Rossi, S., Caiola, S., Verdina, A., Galati, R., Cafolla, A., Crebelli, R. Carcinogenesis (2003) [Pubmed]
  5. Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility. Lee, H.C., Jeong, Y.M., Lee, S.H., Cha, K.Y., Song, S.H., Kim, N.K., Lee, K.W., Lee, S. Hum. Reprod. (2006) [Pubmed]
  6. Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults. Gemmati, D., Ongaro, A., Scapoli, G.L., Della Porta, M., Tognazzo, S., Serino, M.L., Di Bona, E., Rodeghiero, F., Gilli, G., Reverberi, R., Caruso, A., Pasello, M., Pellati, A., De Mattei, M. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  7. Genetic polymorphisms in folate metabolism and the risk of stomach cancer. Zhang, F.F., Terry, M.B., Hou, L., Chen, J., Lissowska, J., Yeager, M., Zatonski, W., Chanock, S., Morabia, A., Chow, W.H. Cancer Epidemiol. Biomarkers Prev. (2007) [Pubmed]
  8. Relationship between run times to exhaustion at 90, 100, 120, and 140% of vVO2max and velocity expressed relatively to critical velocity and maximal velocity. Blondel, N., Berthoin, S., Billat, V., Lensel, G. International journal of sports medicine. (2001) [Pubmed]
  9. Sustained-release methylphenidate for cognitive impairment in HIV-1-infected drug abusers: a pilot study. van Dyck, C.H., McMahon, T.J., Rosen, M.I., O'Malley, S.S., O'Connor, P.G., Lin, C.H., Pearsall, H.R., Woods, S.W., Kosten, T.R. The Journal of neuropsychiatry and clinical neurosciences. (1997) [Pubmed]
  10. Human methionine synthase reductase is a molecular chaperone for human methionine synthase. Yamada, K., Gravel, R.A., Toraya, T., Matthews, R.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida. Doolin, M.T., Barbaux, S., McDonnell, M., Hoess, K., Whitehead, A.S., Mitchell, L.E. Am. J. Hum. Genet. (2002) [Pubmed]
  12. Maternal folate polymorphisms and the etiology of human nondisjunction. Hassold, T.J., Burrage, L.C., Chan, E.R., Judis, L.M., Schwartz, S., James, S.J., Jacobs, P.A., Thomas, N.S. Am. J. Hum. Genet. (2001) [Pubmed]
  13. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Hobbs, C.A., Sherman, S.L., Yi, P., Hopkins, S.E., Torfs, C.P., Hine, R.J., Pogribna, M., Rozen, R., James, S.J. Am. J. Hum. Genet. (2000) [Pubmed]
  14. Molecular dissection of human methionine synthase reductase: determination of the flavin redox potentials in full-length enzyme and isolated flavin-binding domains. Wolthers, K.R., Basran, J., Munro, A.W., Scrutton, N.S. Biochemistry (2003) [Pubmed]
  15. Methylenetetrahydrofolate reductase (MTHFR) 677C>T and methionine synthase reductase (MTRR) 66A>G polymorphisms: association with serum homocysteine and angiographic coronary artery disease in the era of flour products fortified with folic acid. Brilakis, E.S., Berger, P.B., Ballman, K.V., Rozen, R. Atherosclerosis (2003) [Pubmed]
  16. No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers. Chango, A., Fillon-Emery, N., Mircher, C., Bléhaut, H., Lambert, D., Herbeth, B., James, S.J., Réthoré, M.O., Nicolas, J.P. Br. J. Nutr. (2005) [Pubmed]
  17. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Leclerc, D., Wilson, A., Dumas, R., Gafuik, C., Song, D., Watkins, D., Heng, H.H., Rommens, J.M., Scherer, S.W., Rosenblatt, D.S., Gravel, R.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  18. A polymorphism of the methionine synthase reductase gene increases chromosomal damage in peripheral lymphocytes in smokers. Ishikawa, H., Ishikawa, T., Miyatsu, Y., Kurihara, K., Fukao, A., Yokoyama, K. Mutat. Res. (2006) [Pubmed]
  19. CblE type of homocystinuria due to methionine synthase reductase deficiency: clinical and molecular studies and prenatal diagnosis in two families. Zavadakova, P., Fowler, B., Zeman, J., Suormala, T., Pristoupilová, K., Kozich, V., Zavad'áková, P. J. Inherit. Metab. Dis. (2002) [Pubmed]
  20. cblE type of homocystinuria due to methionine synthase reductase deficiency: functional correction by minigene expression. Zavadáková, P., Fowler, B., Suormala, T., Novotna, Z., Mueller, P., Hennermann, J.B., Zeman, J., Vilaseca, M.A., Vilarinho, L., Gutsche, S., Wilichowski, E., Horneff, G., Kozich, V. Hum. Mutat. (2005) [Pubmed]
  21. The repair enzyme peptide methionine-S-sulfoxide reductase is expressed in human epidermis and upregulated by UVA radiation. Ogawa, F., Sander, C.S., Hansel, A., Oehrl, W., Kasperczyk, H., Elsner, P., Shimizu, K., Heinemann, S.H., Thiele, J.J. J. Invest. Dermatol. (2006) [Pubmed]
  22. Percutaneous fiberoptic angioscopy of the cardiac valves. Uchida, Y., Oshima, T., Fujimori, Y., Hirose, J., Mukai, H., Kawashima, M. Am. Heart J. (1991) [Pubmed]
  23. Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia. de Jonge, R., Hooijberg, J.H., van Zelst, B.D., Jansen, G., Jansen, G., van Zantwijk, C.H., van Zantwijk, C.H., Kaspers, G.J., Kaspers, G.J., Peters, G.J., Peters, F.G., Ravindranath, Y., Pieters, R., Lindemans, J. Blood (2005) [Pubmed]
  24. Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI Family Heart Study. Jacques, P.F., Bostom, A.G., Selhub, J., Rich, S., Ellison, R.C., Eckfeldt, J.H., Gravel, R.A., Rozen, R. Atherosclerosis (2003) [Pubmed]
  25. The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. Gaughan, D.J., Kluijtmans, L.A., Barbaux, S., McMaster, D., Young, I.S., Yarnell, J.W., Evans, A., Whitehead, A.S. Atherosclerosis (2001) [Pubmed]
  26. Electron transfer in human methionine synthase reductase studied by stopped-flow spectrophotometry. Wolthers, K.R., Scrutton, N.S. Biochemistry (2004) [Pubmed]
  27. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Olteanu, H., Munson, T., Banerjee, R. Biochemistry (2002) [Pubmed]
  28. Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase. Leal, N.A., Olteanu, H., Banerjee, R., Bobik, T.A. J. Biol. Chem. (2004) [Pubmed]
  29. Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan. Otani, T., Iwasaki, M., Hanaoka, T., Kobayashi, M., Ishihara, J., Natsukawa, S., Shaura, K., Koizumi, Y., Kasuga, Y., Yoshimura, K., Yoshida, T., Tsugane, S. Nutrition and cancer. (2005) [Pubmed]
  30. No association between MTHFR A1298C and MTRR A66G polymorphisms, and MS in an Australian cohort. Szvetko, A.L., Fowdar, J., Nelson, J., Colson, N., Tajouri, L., Csurhes, P.A., Pender, M.P., Griffiths, L.R. J. Neurol. Sci. (2007) [Pubmed]
  31. Effects of single-nucleotide polymorphisms in MTHFR and MTRR on mortality and allograft loss in kidney transplant recipients. Winkelmayer, W.C., Kramar, R., Sunder-Plassmann, G., Födinger, M. Kidney Int. (2005) [Pubmed]
  32. The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida. van der Linden, I.J., den Heijer, M., Afman, L.A., Gellekink, H., Vermeulen, S.H., Kluijtmans, L.A., Blom, H.J. J. Mol. Med. (2006) [Pubmed]
  33. Methionine synthase reductase MTRR 66A > G has no effect on total homocysteine, folate, and Vitamin B12 concentrations in renal transplant patients. Feix, A., Winkelmayer, W.C., Eberle, C., Sunder-Plassmann, G., Födinger, M. Atherosclerosis (2004) [Pubmed]
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