title: Plasma homocysteine is regulated by phospholipid methylation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Noga
authors.forename: Lori M
authors.initials: LM
authors.lastname: Stead
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brosnan
authors.forename: John T
authors.initials: JT
authors.lastname: Brosnan
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Vance
mesh_terms: 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
chemical_list: D010743:Phospholipids; D011994:Recombinant Proteins; D006710:Homocysteine; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase