Packing of cholesterol molecules in human low-density lipoprotein.
High-resolution, proton-decoupled 13C nuclear magnetic resonance spectra (90.55 MHz) of human low-density lipoprotein (LDL) have been employed to investigate the physical state of unesterified cholesterol molecules in this particle. Approximately half of the cholesterol molecules in LDL were replaced with [4-13C]cholesterol by exchange from Celite. About two-thirds of the cholesterol molecules contribute to a resonance at delta 41.8 from the C-4 atom. This signal is assigned to cholesterol molecules located at the surface of the LDL particle in a mixed monolayer with phospholipid molecules; the spin-lattice relaxation of the C-4 nucleus of such cholesterol molecules is enhanced by the presence of Mn2+ ions in the aqueous phase. The remaining one-third of the cholesterol molecules are apparently neither associated with phospholipid nor exposed to the aqueous phase; these cholesterol molecules are presumed to be located in the core of the particle. Cholesterol molecules in the two microenvironments are in slow exchange on the NMR time scale but in fast exchange on a biological time scale, so that the cholesterol molecules in LDL behave physiologically as one pool. There is a loss of about 20% of the intensity of the N(CH3)3 resonance from phosphatidylcholine and sphingomyelin molecules in the LDL spectrum; this is attributed to the presence of apolipoprotein B in the surface of LDL particles, which may immobilize some of the phospholipid polar groups. Spin-lattice relaxation time measurements suggest that the fast axial motions of cholesterol molecules in the surface of LDL are the same as in high-density lipoprotein (HDL).(ABSTRACT TRUNCATED AT 250 WORDS)
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D002152:Calorimetry, Differential Scanning / Q000379:methods; D002247:Carbon Isotopes; D002460:Cell Line; D008078:Cholesterol, LDL / Q000097:blood*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008077:Lipoproteins, LDL / Q000097:blood; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D011973:Receptors, LDL / Q000378:metabolism; D014316:Tritium
D002247:Carbon Isotopes; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014316:Tritium