Role of SAMe in liver health and injury

[Guest guest]

Role of S-adenosyl-L-methionine

in liver health and injury

José M. Mato, C. Lu

CIC-Biogune, Center for

ative Research in Biosciences, CIBER-HEPAD, Parque

Tecnológico de Bizkaia, Derio, Bizkaia   USC Research Center for Liver Diseases,

USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, Keck

School of Medicine USC, Los Angeles, CA

Abstract

S-Adenosylmethionine (SAMe) has rapidly moved from being a methyl donor to a

key metabolite that regulates hepatocyte growth,

death, and differentiation. Biosynthesis of SAMe occurs in all mammalian cells as the first step in methionine catabolism in a reaction catalyzed by methionine adenosyltransferase

(MAT). Decreased hepatic SAMe

biosynthesis is a consequence of all forms of chronic liver injury. In an animal model of chronic liver SAMe

deficiency, the liver is predisposed to further injury and develops

spontaneous steatohepatitis and hepatocellular

carcinoma. However, impaired SAMe

metabolism, which occurs in patients with mutations of glycine

N-methyltransferase (GNMT), can also lead to liver

injury. This suggest that hepatic SAMe level needs to be maintained within a certain range,

and deficiency or excess can both lead to abnormality. SAMe treatment in experimental animal models of liver

injury shows hepatoprotective properties. Meta-analyses also show it is effective in patients with

cholestatic liver diseases. Recent

data show that exogenous SAMe can regulate hepatocyte growth and death, independent of its role as a

methyl donor. This raises the question of its

mechanism of action when used pharmacologically. Indeed,

many of its actions can be recapitulated by methylthioadenosine

(MTA), a by-product of SAMe that is not a methyl

donor. A better understanding of why liver injury

occurs when SAMe homeostasis is perturbed and

mechanisms of action of pharmacologic doses of SAMe

are essential in defining which patients will benefit from its use. (HEPATOLOGY 2007;45:1306-1312.)

Barb in Texas - Together in the Fight, Whatever it Takes!

Son Ken (33) UC 91 - PSC 99 Listed 7/21 @ Baylor Dallas