Functional redundancy of CDP-ethanolamine and CDP-choline pathway enzymes in phospholipid biosynthesis: ethanolamine-dependent effects on steady-state membrane phospholipid composition in Saccharomyces cerevisiae.

It has been established that yeast membrane phospholipid content is responsive to the inositol and choline content of the growth medium. Alterations in the levels of transcription of phospholipid biosynthetic enzymes contribute significantly to this response. We now describe conditions under which ethanolamine can exert significant influence on yeast membrane phospholipid composition. We demonstrate that mutations which block a defined subset of the reactions required for the biosynthesis of phosphatidylcholine (PC) via the CDP-choline pathway cause ethanolamine-dependent effects on the steady-state levels of bulk PC in yeast membranes. Such an ethanolamine-dependent reduction in bulk membrane PC content was observed for both choline kinase (cki) and choline phosphotransferase (cpt1) mutants, but it was not observed for mutants defective in cholinephosphate cytidylyltransferase, the enzyme that catalyzes the penultimate reaction of the CDP-choline pathway for PC biosynthesis. Moreover, the ethanolamine effect observed for cki and cpt1 mutants was independent of the choline content of the growth medium. Finally, we found that haploid yeast strains defective in the activity of both the choline and ethanolamine phosphotransferases experienced an ethanolamine-insensitive reduction in steady-state PC content, an effect which was not observed in strains defective in either one of these activities alone. The collective data indicate that specific enzymes of the CDP-ethanolamine pathway for phosphatidylethanolamine biosynthesis, while able to contribute to PC synthesis when yeast cells are grown under conditions of ethanolamine deprivation, do not do so when yeast cells are presented with this phospholipid headgroup precursor.