Molecular Packing and Fluidity of Lipids in Human Serum Low Density Lipoproteins

Laggner, Peter; Degovics, G.; Müller, Karl; Glatter, Otto; Kratky, O.; Kostner, Gerhard M.; Holasek, A.

doi:10.1515/bchm2.1977.358.2.771

Cited by 57 publications

(39 citation statements)

References 9 publications

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“…Key evidence for the presently most widely accepted model of the neutral lipid core in LDL has come from the combined x-ray and calorimetric studies by Deckelbaum et al (10,11), which was confirmed later by SAXS and SANS data (12,13,36). In all of these studies, little attention has been given to the problem of the packing in the innermost core, mainly because of the above mentioned limitations.…”

Section: Discussionmentioning

confidence: 97%

“…This lipid-melting transition directly affects the molecular packing in the core of LDL, i.e. approximately half of the particle mass (12,13). The local molecular dynamics and polarities in the surface monolayer, including apolipoprotein B, are affected indirectly, such that the transition can be recognized from the particle surface (14,15).…”

mentioning

confidence: 99%

“…The local molecular dynamics and polarities in the surface monolayer, including apolipoprotein B, are affected indirectly, such that the transition can be recognized from the particle surface (14,15). As to the actual transition process, it is generally assumed that it occurs between a low temperature state, in which CE and TG molecules are rigidly packed with their long molecular axes radially arranged in two concentric shells of approximately 36 Å radii each, and a fluid, oily droplet state above the transition (12,13). A quantitative description of the two states and of the processes involved in the transition is still lacking.…”

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confidence: 99%

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Microphase Separation in Low Density Lipoproteins

Pregetter

Ruth

Schuster

et al. 1999

Journal of Biological Chemistry

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The structural organization of the neutral lipid core in human low density lipoproteins (LDL) was investigated in physicochemically defined, distinct human LDL subspecies in the density range of 1.0244 -1.0435 g/ml by evaluation of the core lipid transition temperature, chemical composition, and the behavior of spin-labeled core lipids. Calorimetric studies were performed on more than 60 LDL preparations, and the transition temperature, which varied between 19 and 32°C, was correlated to the chemical composition and revealed a discontinuity at a critical cholesteryl ester to triglyceride ratio of approximately 7:1. For electron spin resonance studies, several LDL preparations were probed with spin-labeled cholesteryl esters and triglycerides, respectively. In LDL with a high triglyceride content, both labels exhibited similar mobility behavior. In contrast, in LDL with only small concentrations of triglycerides, the behavior of labeled cholesteryl esters and labeled triglycerides differed distinctly. The cholesteryl esters were strongly immobilized below the transition temperature, whereas the triglycerides remained fluid throughout the measured temperatures. These results suggest that the critical cholesteryl ester to triglyceride mass ratio of 7:1 corresponds to two concentric compartments with a radial ratio of 2:1, where the liquid triglycerides occupy the core, and the cholesteryl esters form the frozen shell. At higher triglyceride contents, the triglyceride molecules insert into the cholesteryl ester shell and depress the peak transition temperature of the LDL core, whereas at lower triglyceride contents, excess cholesteryl esters are dissolved in the core. Low density lipoproteins (LDL)1 are the major carriers of cholesterol in the circulation and are intimately involved in atherogenesis (1 and references therein). These particles represent complex supramolecular assemblies of phospholipids (ϳ20% of the total mass), free (ϳ12%) and esterified (ϳ40%) cholesterol, triglycerides (ϳ5-10%), and a single copy of apolipoprotein B-100, a glycoprotein of 4,536 amino acids (2-4). In addition, LDL transports minor amounts of lipophilic vitamins and drugs (5). The structure of LDL can be described, in general terms, by a quasispherical core-shell model, in which the apolar constituents (cholesteryl esters (CE) and triglycerides (TG)) form a hydrophobic core of about 150 Å diameter, whereas the phospholipids, most of the unesterified cholesterol, and the apoprotein form an outer surface monolayer with a thickness of about 30 Å (6 -8).In this general sense, LDL would appear to fit readily into the structural core-shell scheme of circulating lipoproteins (9). However, LDL exhibits a distinct physical feature that makes it unique among all structural elements of blood: it is the only component to undergo a major structural transition just below physiological body temperature, in the range between 15 and 32°C (10, 11). The transition temperature varies among individual donors and is correlated to the core lipid compositi...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Microphase Separation in Low Density Lipoproteins

Pregetter

Ruth

Schuster

et al. 1999

Journal of Biological Chemistry

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“…(0). Experimental conditions were identical to those described in detail previously [8,9]. Lipoprotein concentrations: 20 mg/ml; temperature 15 "C for 12 h at 4 "C in the dark with a 0.02 M solution of label I1 in 30 ethanol at a ratio of 6 mol label per lo5 g protein.…”

Section: Methodsmentioning

confidence: 99%

Thermotropic Changes in the Surface Structure of Lipoprotein B from Human‐Plasma Low‐Density Lipoproteins

Laggner¹,

Kostner

1978

European Journal of Biochemistry

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The lipoprotein B fraction of human-plasma low-density lipoproteins was labeled with (a) spin-label analogues of stearic acid I(m/n), the N-oxyl-4',4'-dimethyloxazolidine derivatives of 5-0xo-, 12-0xo-, and 16-oxostearic acid, 1(12/3), 1(5/10), and 1(1/14), respectively, and (b) a spin-label analog of maleimide (3-nialeimido-2,2,5,5-tetramethyl-l-pyrrolidinyloxyl) bound covalently to the protein moiety. Electron spin resonance spectra were measured in the temperature range from 4 "C to 50 "C. The evaluation of the spectra yielded the following results.1. The stearic acid spin labels I(m/n) show a reversible transition in their motional freedom at temperatures between 25 and 30 "C. This effect is stronger for labels I(1/14) and I(5/10) than for 1(12/3). The polarity of their environment decreases in a sigmoidal way between 15 and 40 OC for labels I(12/3) and I(Sjl0). No polarity changes are observed with label 1(1/14).2. Below the transition the motional and polarity characteristics of I(m/n) are dominated by lipidprotein interaction, whereas above 30 "C the spectral parameters approach the situation of a model system of phosphatidylcholine-cholesterol.3 . The protein-bound spin label shows two spectral components arising from weakly and tightly immobilized binding sites, the ratio of the former to the latter increasing strongly between 25 and 30 "C concomitantly with a decrease in the separation of the two signals. The combined results indicate reversible changes in the fine structure involving both protein and polar lipids at the surface of lipoprotein B which correlate to the thermotropic transition of the apolar lipids in the particle core.The physiological role of low-density lipoproteins as the major transport vehicles of cholesterol in human blood [I] and their apparent involvement in the pathophysiology of atherosclerosis [2,3] has stimulated numerous studies directed towards an elucidation of their structure. Most of the existing evidence from chemical and physico-chemical investigations (for a recent review see Laggner [4]) supports a structural model in which the apolar constituents, cholesteryl esters and triglycerides, form the particle core surrounded by the amphiphilic moieties, phospholipids, unesterified cholesterol and protein, forming the external shell. By calorimetric [ S , 61, X-ray [5,7 -91 and spectroscopic techniques [lo, 111 it has been shown that the molecular packing of the cholesteryl esters and triglycerides within the core undergoes a reversible order-disorder transition at temperatures between 15 and 40 "C. Since the temperature course of the transition varies between individuals it has been suggested that this effect might have significance in the catabolism of low-density lipoproteins [6]. Therefore, and in view of the current concepts of recognition, internalization and degradation by target cells [12,3 31, it seems of particular interest to investigate whether this transition affects the surface structure possibly making it recognizable also to receptor binding sites and enzym...

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“…Our present understanding of the structure of LDL particles has emerged from the concerted application of different physico-chemical techniques with early ground-breaking findings derived from neutron-or X-ray small angle scattering data [22][23][24][25] complemented by results from negative staining electron micoscopic (e.m.) [26,27] and spectroscopic techniques [28,29]. For comprehensive reviews on different biophysical studies applied on LDL species see refs.…”

Section: Structural Models Of Ldlmentioning

confidence: 99%