title: Interaction of cholesterol with sphingomyelin in bilayer membranes: evidence that the hydroxy group of sphingomyelin does not modulate the rate of cholesterol exchange between vesicles.
abstract: Cholesterol undergoes exchange between membranes containing sphingomyelin at a much slower rate than between membranes lacking sphingomyelin. To investigate the role of the hydroxy group at the 3-position of sphingomyelin in the interaction between sphingomyelin and cholesterol, we have measured the rates of [4-14C]cholesterol exchange between unilamellar vesicles prepared with N-stearoylsphingomyelin or with synthetic analogues in which the hydroxy group is replaced with an O-alkyl group or with hydrogen. Vesicles prepared from 3-deoxy- and 3-O-methyl-N-stearoylsphingomyelin had the same rate of [14C]-cholesterol desorption. The half-times for exchange from vesicles prepared with 3-O-methyl- and 3-deoxy-N-stearoylsphingomyelins and 10 mol % of cholesterol were only slightly faster (a factor of only 1.5) than that found from vesicles prepared from N-stearoylsphingomyelin and 10 mol % cholesterol. The rate of cholesterol desorption from vesicles could be accelerated by preparing vesicles from bulky 3-O-alkyl analogues of sphingomyelin. Vesicles containing 3-O-ethyl-N-stearoylsphingomyelin and 3-O-tetrahydropyranyl egg sphingomyelin gave rate enhancements of approximately 14 and 35, compared with the rates observed in vesicles made from N-stearoyl- and egg sphingomyelin, respectively. These data indicate that insertion of sterically bulky groups at the 3-position of sphingomyelin (such as ethoxy and tetrahydropyranyloxy) in place of hydroxy interferes markedly with the molecular packing of cholesterol and sphingomyelin in bilayer membranes; however, the hydroxy group of sphingomyelin is not critical for the strong interaction of cholesterol with sphingomyelin.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Chemistry and Biochemistry, Queens College, City University of New York, Flushing 11367.
authors.forename: C C
authors.initials: CC
authors.lastname: Kan
authors.forename: Z S
authors.initials: ZS
authors.lastname: Ruan
authors.forename: R
authors.initials: R
authors.lastname: Bittman
mesh_terms: D000818:Animals; D002151:Calorimetry; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008968:Molecular Conformation; D011865:Radioisotope Dilution Technique; D013109:Sphingomyelins / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D002250:Carbon Radioisotopes; D008051:Lipid Bilayers; D013109:Sphingomyelins; D002784:Cholesterol