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Gene Review

Mat1a  -  methionine adenosyltransferase I, alpha

Mus musculus

Synonyms: AI046368, AdoMet, AdoMet synthase 1, Ams, MAT, ...
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Disease relevance of Mat1a


High impact information on Mat1a

  • Consequently, the ratio of S-adenosylhomocysteine (AdoMet) to S-adenosyl homocysteine (AdoHcy) is reduced threefold in liver [4].
  • Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency [5].
  • These observations predict that under pathological conditions where AdoMet levels are diminished, CBS, and therefore glutathione levels, will be reduced [6].
  • Experiments in isolated rat hepatocytes indicate that AdoMet regulates PHB1 content, thus suggesting ways by which steatohepatitis may be induced [7].
  • Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor [8].

Chemical compound and disease context of Mat1a


Biological context of Mat1a

  • Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged [8].
  • As an initial step toward understanding the control of AdoMet synthetase gene expression, we characterized the complete transcription unit of this gene [13].
  • The AdoMet synthetase gene spans approximately 18 kilobases and consists of nine exons ranging from 78 to 1920 bp [13].
  • The mouse AdoMet synthetase shares 98 and 96% amino acid sequence identity with the adult liver enzyme in the rat and human, respectively [13].
  • The -365 to -2-bp DNA region upstream of the transcription start site of the AdoMet synthetase gene contains promoter elements, and the -518 to -366-bp DNA region might be involved in negative gene regulation [13].

Anatomical context of Mat1a


Associations of Mat1a with chemical compounds


Regulatory relationships of Mat1a


Other interactions of Mat1a

  • Because changes in the AdoMet/AdoHcy ratio could potentially alter the overall excitatory state of the brain, this effect may play a role in the progressive epilepsy seen in the Pcmt1-/- mice [21].
  • Trimethylated peptides acted as a competitive inhibitor to substrate peptide and mixed inhibitor to AdoMet suggesting a random mechanism in a Bi Bi reaction for recombinant G9a where either substrate can bind first to the enzyme, and either product can release first [22].
  • Lipid peroxidation, transforming growth factor-beta (TGFbeta) expression, and decreases in glutathione levels were prevented by AdoMet [2].
  • The changes in the AdoMet/AdoHcy ratio could not be attributed to increases in the activities of methionine adenosyltransferase II or S-adenosylhomocysteine hydrolase in the brain tissue of these mice [21].
  • Drug-induced elevations in ODC and, to a lesser extent, AdoMetDC activities were reversed by later treatment with exogenous AdoMet [23].

Analytical, diagnostic and therapeutic context of Mat1a


  1. Resistance to multiple adenine nucleoside and methionine analogues in mutant murine lymphoma cells with enlarged S-adenosylmethionine pools. Kajander, E.O., Kubota, M., Carrera, C.J., Montgomery, J.A., Carson, D.A. Cancer Res. (1986) [Pubmed]
  2. S-adenosylmethionine blocks collagen I production by preventing transforming growth factor-beta induction of the COL1A2 promoter. Nieto, N., Cederbaum, A.I. J. Biol. Chem. (2005) [Pubmed]
  3. Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. Pakneshan, P., Szyf, M., Farias-Eisner, R., Rabbani, S.A. J. Biol. Chem. (2004) [Pubmed]
  4. Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death. Migchielsen, A.A., Breuer, M.L., van Roon, M.A., te Riele, H., Zurcher, C., Ossendorp, F., Toutain, S., Hershfield, M.S., Berns, A., Valerio, D. Nat. Genet. (1995) [Pubmed]
  5. Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency. Ubagai, T., Lei, K.J., Huang, S., Mudd, S.H., Levy, H.L., Chou, J.Y. J. Clin. Invest. (1995) [Pubmed]
  6. S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity. Prudova, A., Bauman, Z., Braun, A., Vitvitsky, V., Lu, S.C., Banerjee, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine. Santamaria, E., Avila, M.A., Latasa, M.U., Rubio, A., Martin-Duce, A., Lu, S.C., Mato, J.M., Corrales, F.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Lu, S.C., Alvarez, L., Huang, Z.Z., Chen, L., An, W., Corrales, F.J., Avila, M.A., Kanel, G., Mato, J.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Elucidation of the mechanism by which homocysteine potentiates the anti-vaccinia virus effects of the S-adenosylhomocysteine hydrolase inhibitor 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-adenine. Hasobe, M., McKee, J.G., Ishii, H., Cools, M., Borchardt, R.T., De Clercq, E. Mol. Pharmacol. (1989) [Pubmed]
  10. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of S-adenosylmethionine decarboxylase. Bitonti, A.J., Byers, T.L., Bush, T.L., Casara, P.J., Bacchi, C.J., Clarkson, A.B., McCann, P.P., Sjoerdsma, A. Antimicrob. Agents Chemother. (1990) [Pubmed]
  11. Influence of S-adenosylhomocysteine hydrolase inhibitors on S-adenosylhomocysteine and S-adenosylmethionine pool levels in L929 cells. Cools, M., De Clercq, E. Biochem. Pharmacol. (1990) [Pubmed]
  12. Selenite toxicity, depletion of liver S-adenosylmethionine, and inactivation of methionine adenosyltransferase. Hoffman, J.L. Arch. Biochem. Biophys. (1977) [Pubmed]
  13. Cloning and expression of murine S-adenosylmethionine synthetase. Sakata, S.F., Shelly, L.L., Ruppert, S., Schutz, G., Chou, J.Y. J. Biol. Chem. (1993) [Pubmed]
  14. S-adenosylmethionine synthetase is overexpressed in murine neuroblastoma cells resistant to nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase: a novel mechanism of drug resistance. Dwivedi, R.S., Wang, L.J., Mirkin, B.L. Cancer Res. (1999) [Pubmed]
  15. Structure and organization of the human S-adenosylmethionine decarboxylase gene. Marić, S.C., Crozat, A., Jänne, O.A. J. Biol. Chem. (1992) [Pubmed]
  16. Distal motor axonopathy and central nervous system myelin vacuolation caused by cycloleucine, an inhibitor of methionine adenosyltransferase. Lee, C.C., Surtees, R., Duchen, L.W. Brain (1992) [Pubmed]
  17. Impaired liver regeneration in mice lacking methionine adenosyltransferase 1A. Chen, L., Zeng, Y., Yang, H., Lee, T.D., French, S.W., Corrales, F.J., García-Trevijano, E.R., Avila, M.A., Mato, J.M., Lu, S.C. FASEB J. (2004) [Pubmed]
  18. Synthesis of S-adenosylethionine by the gamma isozyme of methionine adenosyltransferase from Friend erythroleukemic cells. Cox, R., Goorha, S. Cancer Res. (1984) [Pubmed]
  19. Relative abilities of bis(ethyl) derivatives of putrescine, spermidine, and spermine to regulate polyamine biosynthesis and inhibit L1210 leukemia cell growth. Porter, C.W., McManis, J., Casero, R.A., Bergeron, R.J. Cancer Res. (1987) [Pubmed]
  20. S-adenosylmethionine (AdoMet) modulates endotoxin stimulated interleukin-10 production in monocytes. Song, Z., Barve, S., Chen, T., Nelson, W., Uriarte, S., Hill, D., McClain, C. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  21. Altered levels of S-adenosylmethionine and S-adenosylhomocysteine in the brains of L-isoaspartyl (D-Aspartyl) O-methyltransferase-deficient mice. Farrar, C., Clarke, S. J. Biol. Chem. (2002) [Pubmed]
  22. Substrate specificity and kinetic mechanism of mammalian G9a histone H3 methyltransferase. Patnaik, D., Chin, H.G., Estève, P.O., Benner, J., Jacobsen, S.E., Pradhan, S. J. Biol. Chem. (2004) [Pubmed]
  23. Modulation of polyamine-biosynthetic activity by S-adenosylmethionine depletion. Kramer, D.L., Sufrin, J.R., Porter, C.W. Biochem. J. (1988) [Pubmed]
  24. Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyl-l-homocysteine. Schatz, R.A., Wilens, T.E., Sellinger, O.Z. J. Neurochem. (1981) [Pubmed]
  25. Regulation of S-adenosylmethionine decarboxylase in L1210 leukemia cells. Studies using an irreversible inhibitor of the enzyme. Autelli, R., Stjernborg, L., Khomutov, A.R., Khomutov, R.M., Persson, L. Eur. J. Biochem. (1991) [Pubmed]
  26. Mechanisms of selenium methylation and toxicity in mice treated with selenocystine. Hasegawa, T., Mihara, M., Nakamuro, K., Sayato, Y. Arch. Toxicol. (1996) [Pubmed]
  27. Acetaminophen-induced suppression of hepatic AdoMet synthetase activity is attenuated by prodrugs of L-cysteine. Shirota, F.N., DeMaster, E.G., Shoeman, D.W., Nagasawa, H.T. Toxicol. Lett. (2002) [Pubmed]
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