Skip to main content
SpringerLink
Log in

A study of the effect of ethanol on the synthesis of serine and the exchange of methyl groups in hepatocytes by NMR spectroscopy

  • Cell Biophysics
  • Published:
Biophysics Aims and scope Submit manuscript

Abstract

The method of NMR spectroscopy was used to investigate the role of voltage-dependent anion channels in the outer mitochondrial membrane in the mechanism of ethanol hepatotoxicity using the synthesis of serine and exchange of methyl groups in hepatocytes metabolizing 13C-labeled glycine. Here we present and describe a methodological approach developed for the independent monitoring of the synthesis of serine in two intracellular compartments: the cytoplasm and mitochondria of intact hepatocytes, and quantification of different serine isotopomers synthesized in hepatocytes from 13C-labeled glycine. The data obtained indicate that the treatment of cells with ethanol as well as cysteamine (specific inhibitor of mitochondrial synthesis of serine) suppressed the level of mitochondrial but not cytoplasmic serine isotopomers. It is concluded that the decrease in the production of mitochondrial serine isotopomers in hepatocytes exposed to ethanol can be caused not only by decreased permeability of the outer mitochondrial membrane due to the closure of voltage-dependent anion channels and suppression of the exchange of substrates of serine synthesis in mitochondria but also by the reduction of the cytoplasmic and/or mitochondrial pool of pyridine nucleotides (NADH) during the oxidation of ethanol. Our work reveals a new mechanism of action of ethanol (alcohol intoxication) in hepatocytes through the regulation of glycine metabolism and opens new possibilities in the treatment of alcohol poisoning.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. C. H. Halsted, J. A. Villanueva, and A. M. Devlin, Alcohol 27, 169 (2002).

    Article  Google Scholar 

  2. C. H. Halsted, J. A. Villanueva, A. M. Devlin, et al., Proc. Natl. Acad. Sci. USA 99, 10072 (2002).

    Article  ADS  Google Scholar 

  3. J. A. Villanueva, A. M. Devlin, and C. H. Halsted, Alcohol. Clin Exp. Res. 25, 415 (2001).

    Article  Google Scholar 

  4. K. L. Schalinske and K. M. Nieman, Nutr. Rev. 63, 387 (2005).

    Article  Google Scholar 

  5. J. B. Mason and S. W. Choi, Alcohol, 35, 235 (2005).

    Article  Google Scholar 

  6. A. I. Cederbaum and J. World, Gastroenterol. 16, 1366 (2010).

    Google Scholar 

  7. N. Tyagi, K. S. Moshal, A. V. Ovechkin, et al., J. Cell Biochem. 96, 665 (2005).

    Article  Google Scholar 

  8. J. C. Fernandez-Checa, A. Colell, and C. Garcia-Ruiz, Alcohol 27, 179 (2002).

    Article  Google Scholar 

  9. S. M Bailey, G. Robinson, A. Pinner, et al., Am. J. Physiol. Gastrointest. Liver Physiol. 291, G857 (2006).

    Article  Google Scholar 

  10. J. Hoek, A. Cahill, and J. Pastorino, Gastroenterology 122, 2049 (2002).

    Article  Google Scholar 

  11. J. C. Fernandez-Checa, N. Kaplowitz, C. Garcia- Ruiz, and A. Colell, Semin. Liver Dis. 18, 389 (1998).

    Article  Google Scholar 

  12. S. K. Mantena, A. L. King, K. K. Andringa, et al., Free Radic. Biol. Med. 44, 1259 (2008).

    Article  Google Scholar 

  13. J. Sastre, G. Serviddio, J. Pereda, et al., Front. Biosci. 12, 1200 (2007).

    Article  Google Scholar 

  14. C. C. Cunningham and S. M. Bailey, Biol. Signals Recept. 10, 271 (2001).

    Article  Google Scholar 

  15. E. Salcedo, P. F. Sims, and J. E. Hyde, Trends Parasitol. 21, 406 (2005).

    Article  Google Scholar 

  16. G. Kikuchi and K. Hiraga, Mol. Cell Biochem. 45, 137. (1982).

    Article  Google Scholar 

  17. D. R. Appling, FASEB J. 5, 2645 (1991).

    MathSciNet  Google Scholar 

  18. J. B. Scheer, A. D. Mackey, and J. F. Gregory, J. Nutr. 135, 233 (2005).

    Google Scholar 

  19. L. B. Pasternack, D.A. Laude, and D. R. Appling, Biochemistry 33, 74 (1994).

    Article  Google Scholar 

  20. J. J. Lemasters and E. Holmuhamedov, Biochim. Biophys. Acta 1762, 181 (2006).

    Google Scholar 

  21. T. P. Theruvath, Z. Zhong, P. Pediaditakis, et al., Hepatology 47, 236 (2008).

    Article  Google Scholar 

  22. E. L. Holmuhamedov and J. J. Lemasters, Arch. Biochem. Biophys. 481, 226 (2009).

    Article  Google Scholar 

  23. M. Colombini, Mol. Cell. Biochem. 256–257, 107 (2004).

    Article  Google Scholar 

  24. M. Colombini, Methods Cell. Biol. 80, 241 (2007).

    Article  Google Scholar 

  25. M. G. Vander Heiden, N. S. Chandel, X. X. Li, et al., Proc. Natl. Acad. Sci. USA 97, 4666 (2000).

    Article  ADS  Google Scholar 

  26. V. Shoshan-Barmatz and D. Gincel, Cell Biochem. Biophys. 39, 279 (2003).

    Article  Google Scholar 

  27. T. Qian, A. L. Nieminen, B. Herman, and J. J. Lemasters, Am. J. Physiol. 273, C1783 (1997).

    Google Scholar 

  28. A. Uchiyama, J. S. Kim, K. Kon, et al., Hepatology 48, 1644 (2008).

    Article  Google Scholar 

  29. L. B. Pasternack, L. E. Littlepage, D. A. Laude, and D. R. Appling, Arch. Biochem. Biophys. 326, 158 (1996).

    Article  Google Scholar 

  30. J. Selhub, J. Nutr. Health Aging 6, 39 (2002).

    Google Scholar 

  31. G. Kikuchi, Y. Motokawa, T. Yoshida, and K. Hiraga, Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 84, 246 (2008).

    Article  Google Scholar 

  32. H. Ogawa, T. Gomi, and M. Fujioka, Int. J. Biochem. Cell Biol. 32, 289 (2000).

    Article  Google Scholar 

  33. G. J. Cowin, D. A. Willgoss, J. Bartley, and Z. H. Endre, Biochim. Biophys. Acta 1310, 32 (1996).

    Article  Google Scholar 

  34. P. C. Nicholas, D. Kim, F. T. Crews, and J. M. Mac-Donald, Anal. Biochem. 358, 185 (2006).

    Article  Google Scholar 

  35. P. C. Nicholas, D. Kim, F. T. Crews, and J. M. Mac-Donald, Chem. Res. Toxicol. 21, 408 (2008).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia

    V. V. Teplova

  2. Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA

    E. L. Holmuhamedov, C. B. Johnson & J. MacDonald

Authors
  1. E. L. Holmuhamedov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. V. Teplova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. B. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. MacDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Original Russian Text ¢ E.L. Holmuhamedov, V.V. Teplova, C.B. Johnson, J. MacDonald, 2010, published in Biofizika, 2010, Vol. 55, No. 6, pp. 1057–1062.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holmuhamedov, E.L., Teplova, V.V., Johnson, C.B. et al. A study of the effect of ethanol on the synthesis of serine and the exchange of methyl groups in hepatocytes by NMR spectroscopy. BIOPHYSICS 55, 966–970 (2010). https://doi.org/10.1134/S0006350910060138

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006350910060138

Keywords

Search

Navigation