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Cited by 94Genetics, Aging, and Longevity in Model OrganismsSulfur Compounds in BiologyFolate and B Vitamins Research

Methionine flux to transsulfuration is enhanced in the long living Ames dwarf mouse

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Uthus, Eric O., Brown-Borg, Holly M.·2006·Mechanisms of Ageing and Development
DOI 10.1016/j.mad.2006.01.001PMC PMC2014095
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Abstract

Long-lived Ames dwarf mice lack growth hormone, prolactin, and thyroid stimulating hormone. Additionally the dwarf mice have enzyme activities and levels that combat oxidative stress more efficiently than those of normal mice. We have shown that methionine metabolism in Ames mice is markedly different than in their wild type littermates. In our previous work we hypothesized that the flux of methionine to the transsulfuration pathway is enhanced in the dwarf mice. The current study was designed to determine whether the flux of methionine to the transsulfuration pathway is increased. We did this by injecting either l-[methyl-(3)H]-methionine or l-[(35)S]-methionine into dwarf or normal mice and then determined retained label (in form of S-adenosylmethionine) 45 min later. The amount of retained hepatic (3)H and (35)S label was significantly reduced in the dwarf mice; at 45 min the specific radioactivity of SAM (pCi/nmol SAM) was 56% lower (p < 0.05) for (3)H-label and 64% lower (p < 0.005) for (35)S-label in dwarf than wild type mice. Retention of (35)S was significantly lower in the brain (37%, p < .04) and kidney (47%, p < 0.02) of the dwarf compared to wild type mice; there was no statistical difference in retained (3)H-label in either brain or kidney. This suggests that both the methyl-moiety and the carbon chain of methionine are lost much faster in the dwarf compared to the wild type mouse, implying that both transmethylation in the liver and transsulfuration in the liver, brain, and kidney are increased in the dwarf mice. As further support, we determined by real-time RT PCR the expression of methionine metabolism genes in livers of mice. Compared to wild type, the Ames dwarf had increased expression of methionine adenosyltransferase 1a (2.3-fold, p = 0.013), glycine N-methyltransferase (3.8-fold, p = 0.023), betaine homocysteine methyltransferase (5.5-fold, p = 0.0006), S-adenosylhomocysteine hydrolase (3.8-fold, p = 0.0005), and cystathionase (2.6-fold; tended to be increased, p = 0.055). Methionine synthase expression was significantly decreased in dwarf compared to wild type (0.48-fold, p = 0.023). These results confirm that the flux of methionine to transsulfuration is enhanced in the Ames dwarf. This, along with data from previous studies support the hypothesis that altered methionine metabolism plays a significant role in the oxidative defense of the dwarf mouse and that the mechanism for the enhanced oxidative defense may be through altered GSH metabolism as a result of the distinctive methionine metabolism.

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  • Multiple longevity interventions in rodents are associated with rewiring of the transsulfuration pathway that feeds into taurine synthesis.

    “Multiple longevity interventions in rodents have been associated with the rewiring of the TSP that feeds into taurine synthesis.34–38”

    From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [35]

    The Discussion (p. 444–450; specific page unavailable) reports greatly enhanced transsulfuration flux in long-lived Ames dwarf mice, supporting this source as one example of altered transsulfuration associated with longevity. It does not address taurine synthesis or establish the claim across multiple longevity interventions; its discussion of a downstream product focuses on glutathione. (LLM, conf=0.83)

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Research works printed but not linked: 31

  1. Aida K, Tawata M, Negishi M, Onaya T. Mouse glycine N-methyltransferase is sexually dimorphic and regulated by growth hormone. Horm Metab Res. 1997;29:646–649. doi: 10.1055/s-2007-978982. [DOI] [PubMed] [Google Scholar] · DOI
  2. Awata S, Nakayama K, Suzuki I, Sugahara K, Kodama H. Changes in cystathionine gamma-lyase in various regions of rat brain during development. Biochem Mol Biol Int. 1995;35:1331–1338. [PubMed] [Google Scholar]
  3. Bottiglieri T. Isocratic high performance liquid chromatographic analysis of S-adenosylmethionine and S-adenosylhomocysteine in animal tissues: the effect of exposure to nitrous oxide. Biomed Chromatogr. 1990;4:239–244. doi: 10.1002/bmc.1130040606. [DOI] [PubMed] [Google Scholar] · DOI
  4. Brown-Borg HM, Bode AM, Bartke A. Antioxidative mechanisms and plasma growth hormone levels: potential relationship in the aging process. Endocrine. 1999;11:41–48. doi: 10.1385/ENDO:11:1:41. [DOI] [PubMed] [Google Scholar] · DOI
  5. Brown-Borg HM, Johnson WT, Razoczy SG, Romanick MA. Mitochondrial oxidant production and oxidative damage in Ames dwarf mice. J Am Aging Assoc. 2001;24:85–96. doi: 10.1007/s11357-001-0012-6. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  6. Brown-Borg HM, Rakoczy SG. Catalase expression in delayed and premature aging mouse models. Exp Gerontol. 2000;35:199–212. doi: 10.1016/s0531-5565(00)00079-6. [DOI] [PubMed] [Google Scholar] · DOI
  7. Brown-Borg HM, Rakoczy SG, Uthus EO. Growth hormone alters methionine and glutathione metabolism in Ames dwarf mice. Mech Ageing Dev. 2005;126:389–398. doi: 10.1016/j.mad.2004.09.005. [DOI] [PubMed] [Google Scholar] · DOI
  8. Carretero MV, Latasa MU, Garcia-Trevijano ER, Corrales FJ, Wagner C, Mato JM, Avila MA. Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine. Biochem Pharmacol. 2001;61:1119–1128. doi: 10.1016/s0006-2952(01)00590-1. [DOI] [PubMed] [Google Scholar] · DOI
  9. Chen Z, Chakraborty S, Banerjee R. Demonstration that mammalian methionine synthases are predominantly cobalamin-loaded. J Biol Chem. 1995;270:19246–19249. doi: 10.1074/jbc.270.33.19246. [DOI] [PubMed] [Google Scholar] · DOI
  10. Cook RJ, Wagner C. Glycine N-methyltransferase is a folate binding protein of rat liver cytosol. Proc Natl Acad Sci USA. 1984;81:3631–3634. doi: 10.1073/pnas.81.12.3631. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  11. Eloranta TO, Kajander EO, Raina AM. A new method for the assay of tissue. S-Adenosylhomocysteine and S-adenosylmethionine. Effect of pyridoxine deficiency on the metabolism of S-adenosylhomocysteine, S-adenosylmethionine and polyamines in rat liver. Biochem J. 1976;160:287–294. doi: 10.1042/bj1600287. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  12. Eloranta TO, Martikainen V, Smith TK. Adaptation of adenosylmethionine metabolism and methionine recycling to variations in dietary methionine in the rat. Proc Soc Exp Biol Med. 1990;194:364–371. doi: 10.3181/00379727-194-43110. [DOI] [PubMed] [Google Scholar] · DOI
  13. Engstrom MA, Benevenga NJ. Rates of oxidation of the methionine and S-adenosylmethionine methyl carbons in isolated rat hepatocytes. J Nutr. 1987;117:1820–1826. doi: 10.1093/jn/117.11.1820. [DOI] [PubMed] [Google Scholar] · DOI
  14. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem. 1990;1:228–237. doi: 10.1016/0955-2863(90)90070-2. [DOI] [PubMed] [Google Scholar] · DOI
  15. Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost. 2000;26:219–225. doi: 10.1055/s-2000-8466. [DOI] [PubMed] [Google Scholar] · DOI
  16. Finkelstein JD, Harris B. Methionine metabolism in mammals: synthesis of S-adenosylhomocysteine in rat tissues. Arch Biochem Biophys. 1973;159:160–165. doi: 10.1016/0003-9861(73)90440-2. [DOI] [PubMed] [Google Scholar] · DOI
  17. Hauck SJ, Hunter WS, Danilovich N, Kopchick JJ, Bartke A. Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse. Exp Biol Med (Maywood) 2001;226:552–558. doi: 10.1177/153537020122600607. [DOI] [PubMed] [Google Scholar] · DOI
  18. Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR. Genome Res. 1996;6:986–994. doi: 10.1101/gr.6.10.986. [DOI] [PubMed] [Google Scholar] · DOI
  19. Hoffmann JL. The rate of transmethylation in mouse liver as measured by trapping S-adenosyl-l-homocysteine. Arch Biochem Biophys. 1980;205:132–135. doi: 10.1016/0003-9861(80)90091-0. [DOI] [PubMed] [Google Scholar] · DOI
  20. Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A. Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003;58:291–296. doi: 10.1093/gerona/58.4.b291. [DOI] [PubMed] [Google Scholar] · DOI
  21. Loehrer FM, Haefeli WE, Angst CP, Browne G, Frick G, Fowler B. Effect of methionine loading on S-methyltetrahydrofolate, S-adenosylmethionine and S-adenosylhomocysteine in plasma of healthy humans. Clin Sci (Colch) 1996;91:79–86. doi: 10.1042/cs0910079. [DOI] [PubMed] [Google Scholar] · DOI
  22. Lu SC, Alvarez L, Huang ZZ, Chen L, An W, Corrales FJ, Avila MA, Kanel G, Mato JM. Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci USA. 2001;98:5560–5565. doi: 10.1073/pnas.091016398. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  23. Martinov MV, Vitvitsky VM, Mosharov EV, Banerjee R, Ataullakhanov FI. A substrate switch: a new mode of regulation in the methionine metabolic pathway. J Theor Biol. 2000;204:521–532. doi: 10.1006/jtbi.2000.2035. [DOI] [PubMed] [Google Scholar] · DOI
  24. Mattison JA, Wright JC, Bronson RT, Roth GS, Ingram DK, Bartke A. Studies of aging in Ames dwarf mice: effects of caloric restriction. J Am Aging Assoc. 2000;23:9–16. doi: 10.1007/s11357-000-0002-0. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  25. Mosharov E, Cranford MR, Banerjee R. The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes. Biochemistry. 2000;39:13005–13011. doi: 10.1021/bi001088w. [DOI] [PubMed] [Google Scholar] · DOI
  26. Ogawa H, Gomi T, Takusagawa F, Fujioka M. Structure, function and physiological role of glycine N-methyltransferase. Int J Biochem Cell Biol. 1998;30:13–26. doi: 10.1016/s1357-2725(97)00105-2. [DOI] [PubMed] [Google Scholar] · DOI
  27. Oscarsson J, Gardmo C, Edén S, Mode A. Pulsatile growth hormone secretion decreases S-adenosylmethionine synthetase in rat liver. Am J Physiol Endocrinol Metab. 2001;280:E280–E286. doi: 10.1152/ajpendo.2001.280.2.E280. [DOI] [PubMed] [Google Scholar] · DOI
  28. Taoka S, Ohja S, Shan X, Kruger WD, Banerjee R. Evidence for heme-mediated redox regulation of human cystathionine beta-synthase activity. J Biol Chem. 1998;273:25179–25184. doi: 10.1074/jbc.273.39.25179. [DOI] [PubMed] [Google Scholar] · DOI
  29. Uthus EO, Brown-Borg HM. Altered methionine metabolism in long living Ames dwarf mice. Exp Gerontol. 2003;38:491–498. doi: 10.1016/s0531-5565(03)00008-1. [DOI] [PubMed] [Google Scholar] · DOI
  30. Wagner C, Briggs WT, Cook RJ. Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism. Biochem Biophys Res Commun. 1985;127:746–752. doi: 10.1016/s0006-291x(85)80006-1. [DOI] [PubMed] [Google Scholar] · DOI
  31. Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects in DNA methylation and gene expression. Cancer Res. 1992;52:2071s–2077s. [PubMed] [Google Scholar]

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Authors
Uthus, E. O., & Brown-Borg, H. M.
Affiliations
Agricultural Research Service (US)
Corresponding author
Uthus, Eric O.
Venue
Mechanisms of Ageing and Development
Publisher
Elsevier BV
Published
2006-05
Volume
127
Issue
5
Pages
444-450
ISSN
0047-6374 (ISSN-L)
DOI
10.1016/j.mad.2006.01.001
PMC
PMC2014095
OpenAlex
W2075798952
Cited by
94
References
0
Citations by year
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FWCI
0.60
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Mechanisms of Ageing and Development (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R15AG022909)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
Keywords
methionine metabolism, transsulfuration pathway, S-adenosylmethionine, glycine N-methyltransferase, betaine-homocysteine methyltransferase, S-adenosylhomocysteine hydrolase, cystathionine gamma-lyase, MAT2A, growth hormone deficiency
MeSH terms
Animals, Antioxidants, Disease Models, Animal, Dwarfism, Female, Glutathione, Humans, Longevity, Male, Methionine, Models, Biological, Sulfur, Time Factors, Reverse Transcriptase Polymerase Chain Reaction, Mice

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