Packing of cholesterol molecules in human high-density lipoproteins
- 13 March 1984
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 23 (6), 1130-1138
- https://doi.org/10.1021/bi00301a015
Abstract
High-resolution, proton-decoulped 13C NMR spectra (90.55 MHz) of human high-density lipoproteins (HDL) were used to investigate the physical state of unesterified cholesterol molecules in such particles. The cholesterol molecules in HDL2 and HDL3 were replaced with [4-13C]cholesterol by either particle reconstitution or exchange from Celite. Two well-defined resonances from [4-13C]cholesterol molecules in HDL2 and HDL3 were observed at chemical shifts (.delta.) of 41.70 and 42.20 ppm, indicating that cholesterol molecules are present in 2 distinct environments. The signal at .delta. 41.70 arises from the C-4 atom of cholesterol molecules asssociated with the phospholipid monolayer at the surface of the particles. The resonance at .delta. 42.20 is due to the 4-13C atom of cholesterol molecules dissolved in the cholesterol ester/triglyceride core. Decomposition of the 2 [4-13C]cholesterol resonances shows that .apprx. 40% of the signal arises from molecules in the apolar core, with the remainder due to molecules in the surface. Spin-lattice relaxation time and line-width measurements indicate that the cholesterol molecules dissolved in the core are relatively disordered and mobile. The cholester molecules located among phospholipid molecules in the surface of the particle undergo relatively restricted, anisotropic motions. The chemical shifts and relaxation enhancements induced by the addition of paramagnetic ions to the aqueous phase indicate that the surface cholesterol molecules in HDL2 and HDL3 are exposed to the water and that the 4-13C atom of cholesterol is located in the region of the phospholipid acylcarboxyl groups. The NMR data indicate that the residence time for cholesterol molecules in either the surface or the core pools of HDL is .gtoreq. 10 ms. However, more than 90% of the unesterified cholesterol molecules in HDL are in a single kinetic pool for exchange with cholesterol molecules in other lipoprotein particles or cells. It follows that cholestrol molecules in the 2 microenvironments undergo fast exchange on the biological time scale and can equilibrate between the surface and core of HDL in the time scale 10 ms to .apprx. 300 s. Neither the surface nor the core microenvironments of human HDL particles are saturated with cholesterol.This publication has 7 references indexed in Scilit:
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