S-adenosylmethionine in Liver Health, Injury, and Cancer
Year: 2012
Type: review
Abstract: 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.
Source: Physiological Reviews
Authors: Shelly C. Lu, José M. Mato
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: hybrid
Awards: Role of SAMe in Pathogenesis and Treatment of Non-Alcholic Fatty Liver Disease, DYSREGULATION OF GSH SYNTHESIS DURING LIVER INJURY AND FIBROSIS, Role of MAT and SAMe in Colon Cancer Pathogenesis and Treatment, USC Research Center for Liver Disease, REGULATION AND FUNCTIONS OF METHIONINE ADENOSYLTRANSFERASE GENES IN LIVER
OpenAlex ID: W2057210916