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Gnmt  -  glycine N-methyltransferase

Rattus norvegicus

Synonyms: Folate-binding protein, Glycine N-methyltransferase
 
 
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Disease relevance of Gnmt

 

High impact information on Gnmt

 

Chemical compound and disease context of Gnmt

  • Introduction of an antisense 24-mer oligonucleotide to glycine N-methyltransferase cDNA into rat hepatoma H4IIE cells by lipofectin resulted in a 60% reduction in the benzo(a)pyrene-mediated induction of ethoxyresorufin-O-deethylase activity and protein over the sense and scrambled antisense oligonucleotide controls [7].
 

Biological context of Gnmt

 

Anatomical context of Gnmt

  • From the structural features of GNMT, we propose that the enzyme might be able to capture yet unidentified molecules in the cytosol and thus participates in various biological processes including detoxification of polycyclic aromatic hydrocarbons [9].
  • Significant GNMT expression is also present in the kidney and pancreas [11].
  • The folate-binding protein of rat liver mitochondria [Zamierowski, M. & Wagner, C. (1977) J. Biol. Chem. 252, 933-938] has been purified to homogeneity by a combination of gel filtration, DEAE-cellulose, and affinity chromatography [6].
  • Intense fluorescence staining for FBP was localized at the apices (brush border) of proximal tubules [12].
  • The choroid plexus, an organ previously shown to contain FBP, also exhibited intense fluorescent staining [12].
 

Associations of Gnmt with chemical compounds

 

Physical interactions of Gnmt

  • The crystal structure of GNMT complexed with AdoMet and acetate, a competitive inhibitor of glycine, has been determined at 2.2 A resolution [9].
 

Other interactions of Gnmt

 

Analytical, diagnostic and therapeutic context of Gnmt

References

  1. Retinoic acid and glucocorticoid treatment induce hepatic glycine N-methyltransferase and lower plasma homocysteine concentrations in rats and rat hepatoma cells. Rowling, M.J., Schalinske, K.L. J. Nutr. (2003) [Pubmed]
  2. Recombinant expression of rat glycine N-methyltransferase and evidence for contribution of N-terminal acetylation to co-operative binding of S-adenosylmethionine. Ogawa, H., Gomi, T., Takata, Y., Date, T., Fujioka, M. Biochem. J. (1997) [Pubmed]
  3. Rat liver nuclei contain receptors for a folate binding protein. da Costa, M., Rothenberg, S.P., Beckman, S.J. Proc. Soc. Exp. Biol. Med. (1983) [Pubmed]
  4. Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Yeo, E.J., Wagner, C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  5. Glycine N-methyltransferase is a folate binding protein of rat liver cytosol. Cook, R.J., Wagner, C. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  6. Identification of folate binding protein of mitochondria as dimethylglycine dehydrogenase. Wittwer, A.J., Wagner, C. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  7. Glycine N-methyltransferase is a mediator of cytochrome P4501A1 gene expression. Raha, A., Joyce, T., Gusky, S., Bresnick, E. Arch. Biochem. Biophys. (1995) [Pubmed]
  8. Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acid. Nieman, K.M., Rowling, M.J., Garrow, T.A., Schalinske, K.L. J. Biol. Chem. (2004) [Pubmed]
  9. Crystal structure of glycine N-methyltransferase from rat liver. Fu, Z., Hu, Y., Konishi, K., Takata, Y., Ogawa, H., Gomi, T., Fujioka, M., Takusagawa, F. Biochemistry (1996) [Pubmed]
  10. Transport of rat liver glycine N-methyltransferase into rat liver nuclei. Krupenko, N.I., Wagner, C. J. Biol. Chem. (1997) [Pubmed]
  11. Activation and induction of glycine N-methyltransferase by retinoids are tissue- and gender-specific. McMullen, M.H., Rowling, M.J., Ozias, M.K., Schalinske, K.L. Arch. Biochem. Biophys. (2002) [Pubmed]
  12. The folate-binding protein of rat kidney. Purification, properties, and cellular distribution. Selhub, J., Franklin, W.A. J. Biol. Chem. (1984) [Pubmed]
  13. Mechanisms for auto-inhibition and forced product release in glycine N-methyltransferase: crystal structures of wild-type, mutant R175K and S-adenosylhomocysteine-bound R175K enzymes. Huang, Y., Komoto, J., Konishi, K., Takata, Y., Ogawa, H., Gomi, T., Fujioka, M., Takusagawa, F. J. Mol. Biol. (2000) [Pubmed]
  14. Crystal structure of apo-glycine N-methyltransferase (GNMT). Pattanayek, R., Newcomer, M.E., Wagner, C. Protein Sci. (1998) [Pubmed]
  15. Phosphorylation modulates the activity of glycine N-methyltransferase, a folate binding protein. In vitro phosphorylation is inhibited by the natural folate ligand. Wagner, C., Decha-Umphai, W., Corbin, J. J. Biol. Chem. (1989) [Pubmed]
  16. 10-Formyltetrahydrofolate dehydrogenase: identification of the natural folate ligand, covalent labeling, and partial tryptic digestion. Wagner, C., Briggs, W.T., Horne, D.W., Cook, R.J. Arch. Biochem. Biophys. (1995) [Pubmed]
  17. Diurnal rhythms of rat liver serine dehydratase, D-site binding protein, and 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels are altered by destruction of the suprachiasmatic nucleus of the hypothalamus. Ogawa, H., Ansai, Y. Arch. Biochem. Biophys. (1995) [Pubmed]
  18. Vitamin A and its derivatives induce hepatic glycine N-methyltransferase and hypomethylation of DNA in rats. Rowling, M.J., McMullen, M.H., Schalinske, K.L. J. Nutr. (2002) [Pubmed]
  19. Alteration of glycine N-methyltransferase activity in fetal, adult, and tumor tissues. Heady, J.E., Kerr, S.J. Cancer Res. (1975) [Pubmed]
  20. Purification and partial characterization of rat liver folate binding protein: cytosol I. Cook, R.J., Wagner, C. Biochemistry (1982) [Pubmed]
 
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