Turnover of Phosphatidylcholine in Saccharomyces cerevisiae

Abstract

The regulation of phosphatidylcholine degradation as a function of the route of phosphatidylcholine (PC) synthesis and changing environmental conditions has been investigated in the yeast Saccharomyces cerevisiae. In the wild-type strains studied, deacylation of phosphatidylcholine to glycerophosphocholine is induced when choline is supplied to the culture medium and, also, when the culture temperature is raised from 30 to 37°C. In strains bearing mutations in any of the genes encoding enzymes of the CDP-choline pathway for phosphatidylcholine biosynthesis (CKI1, choline kinase; CPT1, 1, 2-diacylglycerol choline phosphotransferase; PCT1, CTP:phosphocholine cytidylyltransferase), no induction of phosphatidylcholine turnover and glycerophosphocholine production is seen in response to choline availability or elevated temperature. In contrast, the induction of phosphatidylcholine deacylation does occur in a strain bearing mutations in genes encoding enzymes of the methylation pathway for phosphatidylcholine biosynthesis (i.e. CHO2/PEM1 and OPI3/PEM2). Whereas the synthesis of PC via CDP-choline is accelerated when shifted from 30 to 37°C, synthesis of PC via the methylation pathway is largely unaffected by the temperature shift. These results suggest that the deacylation of PC to GroPC requires an active CDP-choline pathway for PC biosynthesis but not an active methylation pathway. Furthermore, the data indicate that the synthesis and turnover of CDP-choline-derived PC, but not methylation pathway-derived PC, are accelerated by the stress of elevated temperature.

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

“…Recent studies indicate that choline is recycled in the liver and redistributed from kidney, lung (where saturated PC is an essential lipid component of the pulmonary surfactant), and intestine to liver and brain when the choline supply is attenuated (32,33).…”

“…The main fate of choline is the synthesis of PC via the Kennedy pathway, which accounts for up to 95% of the total choline pool in most tissues. The remaining 5% include free choline, phosphocholine, glycerophosphocholine, CDPcholine, and acetylcholine (32,33) as well as other choline-containing phospholipids. The latter include sphingomyelin, choline plasmalogens, and lysophosphatidylcholine; even though less abundant, these species are also involved in maintaining the structural integrity and the signaling functions of cellular membranes.…”

“…The latter include sphingomyelin, choline plasmalogens, and lysophosphatidylcholine; even though less abundant, these species are also involved in maintaining the structural integrity and the signaling functions of cellular membranes. PC serves as a direct substrate for sphingomyelin synthesis via sphingomylein synthases, which transfer the cholinephosphate head group to a ceramide lipid anchor (12,32,33).…”

Glycerophosphocholine Metabolism in Higher Plant Cells. Evidence of a New Glyceryl-Phosphodiester Phosphodiesterase

“…Therefore, the rapid hydrolysis, which involves the action of different lysophospholipases secreted from the aleurone layers Baisted, 1984, 1986;Fujikura and Baisted, 1985), would release quantitative amounts of GroPCho in the endosperm. In addition to germination, we should mention four hypothetical situations that could trigger glycerophosphodiester accumulation in the extracellular compartment: (a) Although there is no evidence of excretion of glycerophosphodiesters in plants, this mechanism is widespread in other eukaryotes like yeast (Angus and Lester, 1975;Dowd et al, 2001) and animal cells (Barburina and Jackowski, 1999); (b) the phospholipid turnover of the plasma membrane may also lead to the production of extracellular glycerophosphodiesters because in yeast, it implies the action of extracellular acyltransferase and phospholipase B (Merkel et al, 1999); van der Rest et al (c) transport of GroPCho through the xylem may occur because Martin and Tolbert (1983) measured high concentrations of P-Cho in the xylem sap; and (d) in physiological situations that affect the plant integrity (wounding, pathogen attack, and senescence), intracellular pools of organic-phosphate are released in the extracellular medium whereas actions of different lipases release phospholipids catabolites. The different phosphatases and phosphodiesterase may allow reuse of various catabolites in the neighborhood of the damaged tissues.…”

“…In yeast (Saccharomyces cerevisiae), glycerophosphodiesters are secreted in the extracellular medium and hydrolyzed at the outer surface of the cell (Patton et al, 1995;Dowd et al, 2001). In animal cells, glycerophosphodiesters, mainly glycerophosphocholine (GroPCho) are synthesized from phospholipids.…”