The role of phosphatidate phosphatase in the biosynthesis of phosphatidylcholine via the CDP‐choline pathway

Abstract

In Saccharomyces cerevisiae, phosphatidylcholine is generated by two different routes, the CDP‐diacylglycerol pathway and the CDP‐choline branch of the Kennedy pathway. The CDP‐choline pathway, which requires diacylglycerol in the last step, plays a critical role when the enzymes in the CDP‐diacylglycerol pathway are defective. In this study, we examined the role of phosphatidate phosphatase in the synthesis of phosphatidylcholine via the CDP‐choline pathway. Lipid analysis showed that diacylglycerol used for the synthesis of the choline‐derived phosphatidylcholine was mainly provided by the PAH1‐encoded phosphatidate phosphatase, which has been shown to play a major role in producing diacylglycerol used for the synthesis of the storage lipid triacylglycerol. The lack of PAH1 in the cho2Δ opi3Δ mutant, which is defective in the CDP‐diacylglycerol pathway, caused a > 50% reduction in the synthesis of phosphatidylcholine via the CDP‐choline pathway. The production of phosphatidylcholine in the cho2Δ opi3Δ pah1Δ mutant indicates the role of as yet unknown enzyme(s) in providing diacylglycerol for phosphatidylcholine synthesis. Supported by NIH grant GM 28140.