Plasma homocysteine is regulated by phospholipid methylation.
Mild hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine, a non-protein amino acid, is formed from S-adenosylhomocysteine and partially secreted into plasma. A potential source for homocysteine is methylation of the lipid phosphatidylethanolamine to phosphatidylcholine by phosphatidylethanolamine N-methyltransferase in the liver. We show that mice that lack phosphatidylethanolamine N-methyltransferase have plasma levels of homocysteine that are approximately 50% of those in wild-type mice. Hepatocytes isolated from methyltransferase-deficient mice secrete approximately 50% less homocysteine. Rat hepatoma cells transfected with phosphatidylethanolamine N-methyltransferase secrete more homocysteine than wild-type cells. Thus, phosphatidylethanolamine N-methyltransferase is an important source of plasma homocysteine and a potential therapeutic target for hyperhomocysteinemia.
Noga
Anna A
AA
Department of Biochemistry and Canadian Institutes for Health Research Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Stead
Lori M
LM
Zhao
Yang
Y
Brosnan
Margaret E
ME
Brosnan
John T
JT
Vance
Dennis E
DE
D000818:Animals; D022781:Hepatocytes / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood* / Q000172:deficiency; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D050918:Phosphatidylethanolamine N-Methyltransferase; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins; D012016:Reference Values; D014162:Transfection
D010743:Phospholipids; D011994:Recombinant Proteins; D006710:Homocysteine; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase