Interrelations between plasma homocysteine and intracellular S-adenosylhomocysteine.
S-Adenosylhomocysteine, a potent intracellular methylation inhibitor, is suggested as a potential mediator for hyperhomocysteinemia-related vascular changes. We investigated the effect of acute and chronic hyperhomocysteinemia 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-adenosylmethionine levels (P > 0.05) in various rat tissues. However intraerythrocyte S-adenosylhomocysteine and S-adenosylmethionine levels were not changed 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 failure patients, who had chronically elevated plasma homocysteine levels, than in either vascular disease patients or healthy controls (P < 0.05). In conclusion, acute hyperhomocysteinemia can increase intracellular S-adenosylhomocysteine levels in tissues actively involved in homocysteine metabolism. The findings are relevant to homocysteine-related endothelial dysfunction since S-adenosylhomocysteine modulates endothelial cell apoptosis.
Fu
W
W
Department of Medicine, Prince Henry/Prince of Wales Hospital and Center for Thrombosis and Vascular Biology, University of New South Wales, Sydney, Australia.
Dudman
N P
NP
Perry
M A
MA
Young
K
K
Wang
X L
XL
D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000097:blood / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014652:Vascular Diseases / Q000097:blood
D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine