Changes in methionine metabolism induced by D-galactosamine in isolated rat hepatocytes |
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| Authors: | M Ozturk F Lemonnier D Cresteil A Lemonnier |
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| Affiliation: | 1. Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115, USA;2. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA;3. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China;4. Key Laboratory of RNA Science and Engineering, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China;5. Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG 30190-009, Brazil;6. Departments of Medicine and Cell Biology, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA;7. Center for Cancer Research, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02129, USA;8. Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA 02139, USA;9. Division of Gastroenterology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA;10. Department of Synthetic Biology and Immunology, National Institute of Chemistry and EN-FIST Centre of Excellence and Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;11. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;12. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA;13. Brigham and Women’s Hospital, Department of Medicine, Cardiovascular Division, Harvard Medical School, Boston, MA 02115, USA;14. Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA |
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| Abstract: | ![]()
We studied several steps of methionine metabolism in isolated rat hepatocytes both with and without the presence of a hepatotoxic agent (D-galactosamine). By use of selective labelling either on methyl or on carboxyl groups, we showed that intracellular methionine is used preferentially for the methylation of phospholipids (42%) and nucleic acids (31%) via S-adenosylmethionine. In the presence of D-galactosamine, the incorporation of L-(14CH3) methionine into macromolecules is significantly inhibited (greater than 50%). This inhibition is associated with a decrease of S-adenosylmethionine and an increase of methionine in the injured cells. These results suggest that hepatotoxicity of galactosamine may be due in part to an inhibition of the methylation of nucleic acids and phospholipids. Consequently, we hypothesize that hypermethioninemia associated with human liver disease could be due, at least partly, to a defect in synthesis and/or utilization of S-adenosylmethionine by hepatocytes. |
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