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Gene Review

AMD1  -  adenosylmethionine decarboxylase 1

Homo sapiens

Synonyms: ADOMETDC, AMD, AdoMetDC, S-adenosylmethionine decarboxylase proenzyme, SAMDC
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Disease relevance of AMD1

  • The current study evaluates the therapeutic effects of antisense ODC and AdoMetDC sequences on colorectal cancer in vitro and in vivo [1].
  • Polyamine depletion by ODC-AdoMetDC antisense adenovirus impairs human colorectal cancer growth and invasion in vitro and in vivo [1].
  • Mammalian S-adenosylmethionine decarboxylase was expressed at a high level in an Escherichia coli mutant deficient in this enzyme [2].
  • Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause of visual impairment in the elderly population, with severe disease affecting nearly 10% of individuals of European descent over the age of 75 years [3].
  • The frequency of severe hepatic toxicity encountered in the early weeks of therapy was 14.3% (five of 35) among patients treated with 60 micrograms/kg of AMD, 3.7% (four of 108) among patients given 45 micrograms/kg, and 2.8% (five of 176) among patients treated with 15 micrograms/kg per dose times five doses (P = .025) [4].

Psychiatry related information on AMD1


High impact information on AMD1


Chemical compound and disease context of AMD1

  • First, the mammalian S-adenosylmethionine decarboxylase produced in E. coli was purified to homogeneity and the pyruvate converted to alanine by a reductive amination [2].
  • To evaluate the effect of dactinomycin (AMD) dose and schedule on the frequency of severe hepatic toxicity in unirradiated National Wilms' Tumor Study-4 (NWTS-4) patients, we reviewed the records of 154 children randomized to single-dose AMD and 176 children randomized to divided-dose AMD administration [4].
  • This differential sensitivity to MGBG suggests that the two enzymes are sufficiently different to warrant the search for compounds that might interfere with the progression of Chagas' disease by selectively inhibiting T. cruzi AdoMetDC [9].
  • Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects [10].
  • RESULTS: In the 291 eyes analyzed, NIR fluorescence was observed in 51 and was graded weak in 27 with wet age-related macular degeneration (AMD, 10 cases), dry AMD with pigment clumping (n=7), chronic central serous choroidopathy (CSC; n=5), choroidal nevi (n=2), subretinal hemorrhages (n=2), and chloroquine maculopathy (n=1) [11].

Biological context of AMD1


Anatomical context of AMD1

  • Proteasome inhibition in COS-7 cells prevents the degradation of S-adenosylmethionine decarboxylase antigen; however, even brief inhibition of the 26 S proteasome caused substantial losses of S-adenosylmethionine decarboxylase activity despite accumulation of S-adenosylmethionine decarboxylase antigen [14].
  • Mutations that remove the uORF, or prevent its initiation, abolish the translational suppression in T cells, establishing that the uORF is a negative element that modulates the cell-specific polysomal distribution of AdoMetDC mRNA [15].
  • We have demonstrated previously that overexpression of AdoMetDC alone is sufficient to transform NIH 3T3 cells and induce highly invasive tumors in nude mice [16].
  • In contrast, non-lymphoid cells normally carry an average of seven to nine ribosomes per AdoMetDC mRNA molecule (Hill, J.R., and Morris, D. R. (1992) J. Biol. Chem. 267, 21886-21893) [17].
  • As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD [18].

Associations of AMD1 with chemical compounds


Regulatory relationships of AMD1


Other interactions of AMD1

  • The ODC, ADOMETDC, and SPDSYN overproducer strains exhibited a high level of resistance to difluoromethylornithine, 5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine, and n-butylamine, respectively, confirming previous observations that these agents specifically target polyamine enzymes [22].
  • In accordance with the human AdoMetDC, the C50A and C230A mutagenesis had minimal effect on catalytic activity, which was further supported by DTNB-mediated inactivation and reactivation [23].
  • We have studied the effects of altering these elements on both the expression of AdoMetDC and its regulation by n-butyl-1,3-diaminopropane (BDAP), a spermine synthase inhibitor [24].
  • Cell-specific translation of AdoMetDC appears to be regulated exclusively through the internal ORF, which causes ribosome stalling that is independent of eIF-4E levels and decreases the efficiency with which the downstream ORF encoding AdoMetDC protein is translated [25].

Analytical, diagnostic and therapeutic context of AMD1


  1. Polyamine depletion by ODC-AdoMetDC antisense adenovirus impairs human colorectal cancer growth and invasion in vitro and in vivo. Zhang, B., Liu, X.X., Zhang, Y., Jiang, C.Y., Hu, H.Y., Gong, L., Liu, M., Teng, Q.S. The journal of gene medicine. (2006) [Pubmed]
  2. Site of pyruvate formation and processing of mammalian S-adenosylmethionine decarboxylase proenzyme. Stanley, B.A., Pegg, A.E., Holm, I. J. Biol. Chem. (1989) [Pubmed]
  3. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Hughes, A.E., Orr, N., Esfandiary, H., Diaz-Torres, M., Goodship, T., Chakravarthy, U. Nat. Genet. (2006) [Pubmed]
  4. Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study. Green, D.M., Norkool, P., Breslow, N.E., Finklestein, J.Z., D'Angio, G.J. J. Clin. Oncol. (1990) [Pubmed]
  5. Brain S-adenosylmethionine decarboxylase activity is increased in Alzheimer's disease. Morrison, L.D., Bergeron, C., Kish, S.J. Neurosci. Lett. (1993) [Pubmed]
  6. Degrees of malignancy in human primary central nervous system tumors: ornithine decarboxylase levels as better indicators than adenosylmethionine decarboxylase levels. Scalabrino, G., Modena, D., Ferioli, M.E., Puerari, M., Luccarelli, G. J. Natl. Cancer Inst. (1982) [Pubmed]
  7. c-Jun activation-dependent tumorigenic transformation induced paradoxically by overexpression or block of S-adenosylmethionine decarboxylase. Paasinen-Sohns, A., Kielosto, M., Kääriäinen, E., Eloranta, T., Laine, A., Jänne, O.A., Birrer, M.J., Hölttä, E. J. Cell Biol. (2000) [Pubmed]
  8. Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in vivo. Yang, L., Jackson, E., Woerner, B.M., Perry, A., Piwnica-Worms, D., Rubin, J.B. Cancer Res. (2007) [Pubmed]
  9. Trypanosoma cruzi has not lost its S-adenosylmethionine decarboxylase: characterization of the gene and the encoded enzyme. Persson, K., Aslund, L., Grahn, B., Hanke, J., Heby, O. Biochem. J. (1998) [Pubmed]
  10. The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older. Khachik, F., de Moura, F.F., Chew, E.Y., Douglass, L.W., Ferris, F.L., Kim, J., Thompson, D.J. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  11. Fundus near infrared fluorescence correlates with fundus near infrared reflectance. Weinberger, A.W., Lappas, A., Kirschkamp, T., Mazinani, B.A., Huth, J.K., Mohammadi, B., Walter, P. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  12. Structure and activity of mouse S-adenosylmethionine decarboxylase gene promoters and properties of the encoded proteins. Nishimura, K., Liisanantti, M., Muta, Y., Kashiwagi, K., Shirahata, A., Jänne, M., Kankare, K., Jänne, O.A., Igarashi, K. Biochem. J. (1998) [Pubmed]
  13. The human S-adenosylmethionine decarboxylase gene: nucleotide sequence of a pseudogene and chromosomal localization of the active gene (AMD1) and the pseudogene (AMD2). Maric, S.C., Crozat, A., Louhimo, J., Knuutila, S., Jänne, O.A. Cytogenet. Cell Genet. (1995) [Pubmed]
  14. S-adenosylmethionine decarboxylase degradation by the 26 S proteasome is accelerated by substrate-mediated transamination. Yerlikaya, A., Stanley, B.A. J. Biol. Chem. (2004) [Pubmed]
  15. Cell-specific translation of S-adenosylmethionine decarboxylase mRNA. Regulation by the 5' transcript leader. Hill, J.R., Morris, D.R. J. Biol. Chem. (1992) [Pubmed]
  16. Cysteine cathepsins are central contributors of invasion by cultured adenosylmethionine decarboxylase-transformed rodent fibroblasts. Ravanko, K., Järvinen, K., Helin, J., Kalkkinen, N., Hölttä, E. Cancer Res. (2004) [Pubmed]
  17. Cell-specific translational regulation of S-adenosylmethionine decarboxylase mRNA. Dependence on translation and coding capacity of the cis-acting upstream open reading frame. Hill, J.R., Morris, D.R. J. Biol. Chem. (1993) [Pubmed]
  18. Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration. Harris, A., Chung, H.S., Ciulla, T.A., Kagemann, L. Progress in retinal and eye research. (1999) [Pubmed]
  19. Amino acid residues necessary for putrescine stimulation of human S-adenosylmethionine decarboxylase proenzyme processing and catalytic activity. Stanley, B.A., Pegg, A.E. J. Biol. Chem. (1991) [Pubmed]
  20. Role of cysteine-82 in the catalytic mechanism of human S-adenosylmethionine decarboxylase. Xiong, H., Stanley, B.A., Pegg, A.E. Biochemistry (1999) [Pubmed]
  21. S-adenosylmethionine decarboxylase activity and utilization of exogenous putrescine are enhanced in colon cancer cells stimulated to grow by EGF. Milovic, V., Turhanowa, L., Fares, F.A., Lerner, A., Caspary, W.F., Stein, J. Zeitschrift für Gastroenterologie. (1998) [Pubmed]
  22. Leishmania donovani Polyamine Biosynthetic Enzyme Overproducers as Tools To Investigate the Mode of Action of Cytotoxic Polyamine Analogs. Roberts, S.C., Jiang, Y., Gasteier, J., Frydman, B., Marton, L.J., Heby, O., Ullman, B. Antimicrob. Agents Chemother. (2007) [Pubmed]
  23. Structural roles of cysteine 50 and cysteine 230 residues in Arabidopsis thaliana S-adenosylmethionine decarboxylase. Park, S.J., Cho, Y.D. J. Biochem. Mol. Biol. (2002) [Pubmed]
  24. Role of the 5'-untranslated region of mRNA in the synthesis of S-adenosylmethionine decarboxylase and its regulation by spermine. Shantz, L.M., Viswanath, R., Pegg, A.E. Biochem. J. (1994) [Pubmed]
  25. Translational regulation of ornithine decarboxylase and other enzymes of the polyamine pathway. Shantz, L.M., Pegg, A.E. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  26. S-adenosylmethionine decarboxylase from Leishmania donovani. Molecular, genetic, and biochemical characterization of null mutants and overproducers. Roberts, S.C., Scott, J., Gasteier, J.E., Jiang, Y., Brooks, B., Jardim, A., Carter, N.S., Heby, O., Ullman, B. J. Biol. Chem. (2002) [Pubmed]
  27. Expression of mammalian S-adenosylmethionine decarboxylase in Escherichia coli. Determination of sites for putrescine activation of activity and processing. Stanley, B.A., Shantz, L.M., Pegg, A.E. J. Biol. Chem. (1994) [Pubmed]
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