SAMe (S-adenosylmethionine) is the main methyl donor group in the cell. MAT (methionine adenosyltransferase) is the unique enzyme responsible for the synthesis of SAMe from methionine and ATP, and SAMe is the common point between the three principal metabolic pathways: polyamines, transmethylation and transsulfuration that converge into the methionine cycle. SAMe is now also considered a key regulator of metabolism, proliferation, differentiation, apoptosis and cell death. Recent results show a new signalling pathway implicated in the proliferation of the hepatocyte, where AMPK (AMP-activated protein kinase) and HuR, modulated by SAMe, take place in HGF (hepatocyte growth factor)-mediated cell growth. Abnormalities in methionine metabolism occur in several animal models of alcoholic liver injury, and it is also altered in patients with liver disease. Both high and low levels of SAMe predispose to liver injury. In this regard, knockout mouse models have been developed for the enzymes responsible for SAMe synthesis and catabolism, MAT1A and GNMT (glycine N-methyltransferase) respectively. These knockout mice develop steatosis and HCC (hepatocellular carcinoma), and both models closely replicate the pathologies of human disease, which makes them extremely useful to elucidate the mechanism underlying liver disease. These new findings open a wide range of possibilities to discover novel targets for clinical applications.
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October 2008
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Conference Article|
September 19 2008
S-adenosylmethionine and proliferation: new pathways, new targets
Nuria Martínez-López;
Nuria Martínez-López
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Marta Varela-Rey;
Marta Varela-Rey
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Usue Ariz;
Usue Ariz
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Nieves Embade;
Nieves Embade
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Mercedes Vazquez-Chantada;
Mercedes Vazquez-Chantada
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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David Fernandez-Ramos;
David Fernandez-Ramos
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Laura Gomez-Santos;
Laura Gomez-Santos
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Shelly C. Lu;
Shelly C. Lu
†Keck School of Medicine, USC (University of Southern California), Los Angeles, CA 90089, U.S.A.
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Jose M. Mato;
Jose M. Mato
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
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Maria L. Martinez-Chantar
Maria L. Martinez-Chantar
1
*Unidad de Metabolómica, CIC bioGUNE (Asociacion Centro de Investigación Cooperativa en Biociencias), Parque Tecnológico de Bizkaia, Edificio 801A, 48160 Derio (Bizkaia), Spain
1To whom any correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 07 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (5): 848–852.
Article history
Received:
March 07 2008
Citation
Nuria Martínez-López, Marta Varela-Rey, Usue Ariz, Nieves Embade, Mercedes Vazquez-Chantada, David Fernandez-Ramos, Laura Gomez-Santos, Shelly C. Lu, Jose M. Mato, Maria L. Martinez-Chantar; S-adenosylmethionine and proliferation: new pathways, new targets. Biochem Soc Trans 1 October 2008; 36 (5): 848–852. doi: https://doi.org/10.1042/BST0360848
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