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Early effects of copper accumulation on methionine metabolism

AuthorsDelgado, Miguel ; Pérez-Miguelsanz, Juliana; Garrido, Francisco ; Rodríguez-Tarduchy, Gemma ; Pérez-Sala, Dolores ; Pajares, María A.
KeywordsMethionine metabolism
Methionine adenosyltransferase
Copper accumulation
Wilson's disease
S-adenosylhomocysteine hydrolase
Issue Date2008
CitationCellular and Molecular Life Sciences 65(13): 2080-2090 (2008)
AbstractWilson’s disease is characterized by long-term hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model early alterations in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle were detected. Noteworthy, the main change was a redox mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases.
DescriptionEl pdf del artículo es la versión de autor.
Publisher version (URL)http://dx.doi.org/10.1007/s00018-008-8201-4
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