Farnesol inhibits phosphatidylcholine biosynthesis in cultured cells by decreasing cholinephosphotransferase activity. 1993

P A Voziyan, and C M Goldner, and G Melnykovych
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66103.

The mechanism of inhibition of phosphatidylcholine (PC) biosynthesis by the isoprenoid farnesol was investigated in the human leukaemic CEM-C1 cell line. Cells were preincubated with 20 microM farnesol for up to 2 h and pulsed with [3H]choline. PC biosynthesis was inhibited to one-quarter at the step catalysed by cholinephosphotransferase (CPT). CPT activity in cellular homogenates from farnesol-treated cells was significantly decreased, but no changes in cytidylyltransferase activity or diacylglycerol concentration were observed. Measurements of CPT activity in the experiments in which farnesol was added directly to the homogenates or microsomal fractions demonstrated that farnesol did not affect CPT activity. However, cytosol from farnesol-treated samples decreased microsomal CPT activity almost twice as much as did cytosol from controls. This effect was found to be heat-stable, and disappeared after dialysis, but could not be attributed to farnesol present in the cytosol. The effect of farnesol was specific when compared with other structurally similar isoprenoids. We conclude that farnesol brings about changes in cultured cells, leading to decreased CPT activity, and thus to the inhibition of PC biosynthesis.

UI MeSH Term Description Entries
D007938 Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006) Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D009713 Nucleotidyltransferases A class of enzymes that transfers nucleotidyl residues. EC 2.7.7. Nucleotidyltransferase
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D002798 Diacylglycerol Cholinephosphotransferase An enzyme that catalyzes the synthesis of phosphatidylcholines from CDPcholine and 1,2-diacylglycerols. EC 2.7.8.2. Cholinephosphotransferase,Phosphorylcholine-Glyceride Transferase,1-alkyl-2-Acetylglycerol Cholinephosphotransferase,CDP-Choline 1,2-Diglyceride Choline Phosphotransferase,CDP-Choline Cholinephosphotransferase,CDP-Diacylglycerol Synthase,Diacylglycerol-CDP Choline Phosphotransferase,PAF Phosphocholinetransferase,Phosphocholinetransferase,Phosphorylcholineglyceride Transferase,CDP Choline 1,2 Diglyceride Choline Phosphotransferase,CDP Choline Cholinephosphotransferase,CDP Diacylglycerol Synthase,Choline Phosphotransferase, Diacylglycerol-CDP,Cholinephosphotransferase, 1-alkyl-2-Acetylglycerol,Cholinephosphotransferase, CDP-Choline,Cholinephosphotransferase, Diacylglycerol,Diacylglycerol CDP Choline Phosphotransferase,Phosphocholinetransferase, PAF,Phosphorylcholine Glyceride Transferase,Phosphotransferase, Diacylglycerol-CDP Choline,Synthase, CDP-Diacylglycerol,Transferase, Phosphorylcholine-Glyceride,Transferase, Phosphorylcholineglyceride
D004075 Diglycerides Glycerides composed of two fatty acids esterified to the trihydric alcohol GLYCEROL. There are two possible forms that exist: 1,2-diacylglycerols and 1,3-diacylglycerols. Diacylglycerol,Diacylglycerols
D005204 Farnesol A colorless liquid extracted from oils of plants such as citronella, neroli, cyclamen, and tuberose. It is an intermediate step in the biological synthesis of cholesterol from mevalonic acid in vertebrates. It has a delicate odor and is used in perfumery. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D050356 Lipid Metabolism Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS. Metabolism, Lipid

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