Importance of a deficiency in S-adenosyl-L-methionine synthesis in the pathogenesis of liver injury

Am J Clin Nutr. 2002 Nov;76(5):1177S-82S. doi: 10.1093/ajcn/76/5.1177S.

Abstract

One of the features of liver cirrhosis is an abnormal metabolism of methionine--a characteristic that was described more than a half a century ago. Thus, after an oral load of methionine, the rate of clearance of this amino acid from the blood is markedly impaired in cirrhotic patients compared with that in control subjects. Almost 15 y ago we observed that the failure to metabolize methionine in cirrhosis was due to an abnormally low activity of the enzyme methionine adenosyltransferase (EC 2.5.1.6). This enzyme converts methionine, in the presence of ATP, to S-adenosyl-L-methionine (SAMe), the main biological methyl donor. Since then, it has been suspected that a deficiency in hepatic SAMe may contribute to the pathogenesis of the liver in cirrhosis. The studies reviewed here are consistent with this hypothesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Liver Cirrhosis / etiology*
  • Methionine Adenosyltransferase / genetics
  • Methionine Adenosyltransferase / metabolism
  • Nitric Oxide / physiology
  • Reactive Oxygen Species / metabolism
  • S-Adenosylmethionine / biosynthesis
  • S-Adenosylmethionine / deficiency*
  • S-Adenosylmethionine / therapeutic use

Substances

  • Isoenzymes
  • Reactive Oxygen Species
  • Nitric Oxide
  • S-Adenosylmethionine
  • Methionine Adenosyltransferase