Journal
PHYSIOLOGICAL REVIEWS
Volume 92, Issue 4, Pages 1515-1542Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physrev.00047.2011
Keywords
-
Categories
Funding
- National Institutes of Health [R01DK51719, R01DK092407, P30DK48522, R01AT1576, R01AT004896]
- Plan Nacional of I + D [SAF 2011-29851]
- Departamento de Educacion Gobierno Vasco
Ask authors/readers for more resources
Lu SC, Mato JM. S-adenosylmethionine in Liver Health, Injury, and Cancer. Physiol Rev 92: 1515-1542, 2012; doi:10.1152/physrev.00047.2011.-S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available