Interrelations between plasma homocysteine and intracellular S-adenosylhomocysteine

S-Adenosylhomocysteine, a potent intracellular methylation inhibitor, is su ggested as a potential mediator for hyperhomocysteinemia-related vascular c hanges. We investigated the effect of acute and chronic hyperhomocysteinemi a on intracellular S-adenosylhomocysteine and S-adenosylmethionine in rats and humans. Elevated plasma homocysteine in rats infused with homocysteine produced an increase in S-adenosylhomocysteine (P < 0.001) but not S-adenos ylmethionine levels (P > 0.05) in various rat tissues. However intraerythro cyte S-adenosylhomocysteine and S-adenosylmethionine levels were not change d in homocysteine-infused rats and human subjects with experimentally acute hyperhomocysteinemia by methionine loading test. In contrast, erythrocyte S-adenosylhomocysteine levels were significantly higher in chronic renal fa ilure patients, who had chronically elevated plasma homocysteine levels, th an in either vascular disease patients or healthy controls (P < 0.05). In c onclusion, acute hyperhomocysteinemia can increase intracellular S-adenosyl homocysteine levels in tissues actively involved in homocysteine metabolism . The findings are relevant to homocysteine-related endothelial dysfunction since S-adenosylhomocysteine modulates endothelial cell apoptosis. (C) 200 0 Academic Press.