3-Deazaadenosine and MDL29350 differentially affect the methylation of serine-and ethanolamine-derived phosphatidylethanolamine in Hep G2 cells.

The effect of 3-deazaadenosine (DZA) and the hypolipidemic drug MDL29350 (2-[3,5-di(t-butyl-4-hydroxyphenyl)thio]hexanoic acid) on the synthesis and methylation of phosphatidylethanolamine (PE) originating from the cytidine diphosphate (CDP) ethanolamine pathway and PE originating from decarboxylation of phosphatidylserine (PS) was investigated. DZA and MDL29350 did not affect the synthesis of PE by either pathway; however, methylation of ethanolamine-derived PE was inhibited by 80% and methylation of serine-derived PE was inhibited by 36% by 20 mumol/LDZA or MDL29350. The differential inhibition of the methylation of PE synthesized via serine or ethanolamine suggests that in Hep G2 cells PE-N-methyltransferase (PENMT) may be segregated into distinct compartments that are differentially accessible to the drugs.