Metabolism of exogenous S-adenosyl-L-methionine in patients with liver disease

Abstract

S-Adenosyl-L-methionine (SAMe) is an important methyl group donor for many biochemical reactions. It is widespread in body tissues, including the liver, and is metabolised via 3 main metabolic pathways: transmethyltion, trans-sulphuration and amino-propylation. In chronic liver disease these pathways are impaired, the major abnormality being a reduction in SAMe-synthetase activity. Exogenous SAMe may overcome the effects of impaired SAMe-synthetase activity. Exogenous SAMe is stable in digestive juices and, although well absorbed orally, bioavailability is reduced because of a significant first pass effect in the liver. Dose-dependent peak plasma levels are achieved within 3 to 6 hours of oral administration and plasma levels approach baseline after 24 hours. Volumes of distribution are small. The metabolism of exogenous SAMe appears to follow the known pathways of endogenous SAMe metabolism and the initial data suggest that the process is largely unaffected in patients with chronic liver disease.