Increasing the levels of ether-linked lipids in L-M cells by glyceryl ether supplementation depresses growth and choline utilization.
To gain insight into the role of alkyl-linked lipids in biological systems, we added hexadecylglycerol (a precursor of complex ether-linked lipids) to medium required for the growth of L-M cells in culture. L-M fibroblasts cultured through several generations in the presence of hexadecylglycerol grow at a reduced rate. Experimental cells at their sixth passage, with 2 microgram supplement/ml, double at 50% the rate of control cell populations. Hexadecylglycerol (10 microgram/ml) added 1 day after cell passage does not retard growth; however, within 1 h it decreases the incorporation of choline into the choline glycerophosphatide fraction. Inhibition is specific for choline; ethanolamine incorporation is not affected. The inhibition of choline utilization by hexadecylglycerol-treated cells is dose-dependent and reaches a maximum 12 h after supplementation. Cellular uptake of choline is reduced (approx. 17%) but not as much as the incorporation of choline into the phospholipids (approx. 60% at 12 h). The assimilation of ether lipid precursor into cellular phospholipids was followed by incubating cells with [1-14C]hexadecylglycerol. Incorporation of radioactivity into cellular phospholipids begins to plateau after 24 h, whereas the interference of hexadecylglycerol with choline metabolism could be detected as early as 1 h. The majority of the radioactivity recovered from cells incubated with labeled hexadecylglycerol is localized in the microsomal fraction (56%), where the label was distributed as free hexadecyglycerol, alkylacyl-phospholipids and alkyldiacylglycerols. These results show that the supplementation of a glyceryl ether to L-M fibroblast growth media selectively inhibits the utilization of choline for choline glycerophospholipid biosynthesis and causes a reduction in cell growth rate when cells are continually passaged in the presence of the glyceryl ether.
D002794:Choline / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005995:Glyceryl Ethers; D007739:L Cells / Q000378:metabolism* / Q000502:physiology; D050356:Lipid Metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis
D004983:Ethanolamines; D005995:Glyceryl Ethers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D019856:Ethanolamine; D002794:Choline; D005990:Glycerol; C004348:chimyl alcohol