Structural requirements of the phospholipid substrate for phospholipid N-methylation in rat liver.
The role of endogenous phospholipid substrates for phospholipid methylation was investigated in rat liver microsomes. The amount of phosphatidylethanolamine could be drastically reduced by treatment of microsomes with an amino group-blocking compound, methylacetimidate. Simultaneously, the formation of labelled phospholipids from S-adenosyl[Me-3H]methionine decreased, indicating that the amount of endogenous substrate influenced the reaction rate. Phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine and phosphatidylmonoethylethanolamine added as dispersions to untreated or treated microsomes stimulated phospholipid methylation, whereas several other phospholipids were inactive. In other experiments the role of phospholipid substrates in intact cells was studied. Cultured rat hepatocytes were enriched in different phospholipids by preincubation with different amino alcohols, and the effects of phospholipid methylation was measured by incubation with [Me-14C]methionine. Phospholipid methylation was significantly stimulated after preincubation with ethanolamine, monomethylethanolamine, monoethylethanolamine and 2-aminobutanol. The results show that both the number and chain length of N-alkyl substituents on phosphatidylethanolamine, as well as other changes in the ethanolamine moiety, will affect the ability of different phospholipids to act as methyl acceptors.
D000818:Animals; D002478:Cells, Cultured; D007096:Imidoesters / Q000494:pharmacology; D007202:Indicators and Reagents / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000378:metabolism; D013329:Structure-Activity Relationship
D007096:Imidoesters; D007202:Indicators and Reagents; D010743:Phospholipids; D012436:S-Adenosylmethionine; C010222:methyl acetimidate