Lipoproteins lipid monolayer

Cl. Camejo, G., Suarez, Z. M., and Munoz, V., The apolipoproteins of human plasma high density lipoprotein a study of their lipid-binding capacity and interaction with lipid monolayers. Biochim. Biophys. Acta 218, 155-166 (1970). 

D3g-dodecylphosphocholine (DPC) micelles were used to provide a lipid environment. This molecule, which possesses a phosphocholine head group and a single Ci2 hydrocarbon chain, mimics the phospholipid component of lipoprotein surface monolayers. About 40 DPC molecules form a micelle which has molecular weight of about 16 kDa. Thus, the apoLp-IH/DPC (1 1 protein/micelle) complex... 

The surface of all lipoproteins consists of a lipid monolayer containing all the PL, and about 2/3 of all unesterified cholesterol, plus the corresponding apolipoproteins. 

Interactions of apolipoproteins with PL are essential for the assembly of lipoproteins, stabilization of lipoprotein structures, and expression and modulation of apolipoprotein functions. The main experimental approaches for the study of apolipoprotein interactions with PL have used isolated, exchangeable apolipoproteins in conjunction with aggregated lipids dispersed in water or spread at the air-water interface. The aggregated lipid states include lipid monolayers, various types of liposomes (small unilamellar vesicles, large unilamellar vesicles, multilamellar vesicles), and emulsions. All these lipid systems consist of or include PL, especially PC. 

Staining Applications Axons bovine brain tissues mitral/tufted cells retinal ganglion cells bacteria cells lipid bilayers lipid monolayers lipid membranes lipoproteins liposomes membranes neurons neural tracers vessel peptides proteins antibodies ... 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

Lipoproteins are an important class of serum proteins in which a spherical hydrophobic core of triglycerides or cholesterol esters is surrounded by an amphipathic monolayer of phospholipids, cholesterol and apolipoproteins (fatbinding proteins). Lipoproteins transport lipid in the circulation and vary in size and density, depending on their proteindipid ratio (Figure 7.3). Lipoprotein metabolism is adversely affected by obesity low-density lipoprotein (LDL)-cholesterol and plasma triglyceride are increased, together with decreased high-density lipoprotein (HDL)-cholesterol concentrations. 

The apoproteins of HDL are secreted by the liver and intestine. Much of the lipid comes from the surface monolayers of chylomicrons and VLDL during lipolysis. HDL also acquire cholesterol from peripheral tissues in a pathway that protects the cholesterol homeostasis of cells. In this process, free cholesterol is transported from the cell membrane by a transporter protein, ABCA1, acquired by a small particle termed prebeta-1 HDL, and then esterified by lecithin cholesterol acyltransferase (LCAT), leading to the formation of larger HDL species. The cholesteryl esters are transferred to VLDL, IDL, LDL, and chylomicron remnants with the aid of cholesteryl ester transfer protein (CETP). Much of the cholesteryl ester thus transferred is ultimately delivered to the liver by endocytosis of the acceptor lipoproteins. HDL can also deliver cholesteryl esters directly to the liver via a docking receptor (scavenger receptor, SR-BI) that does not endocytose the lipoproteins. 

The general structure of lipoproteins is shown schematically in Figure 3. The core of the lipoprotein contains the more hydrophobic lipids namely cholesterol ester (CE) and triglyceride (TG) and is surrounded by a surface monolayer consisting of the more polar phospholipid (PL) and free cholesterol (FC). Apoproteins are associated with the lipoprotein surface. The proportional composition of human plasma lipoproteins is given in Table 7. 

Figure 3 Schematic representation of a lipoprotein particle. The core in made up of hydrophobic lipids (TG and CE) surrounded by a monolayer of phospholipids and free cholesterol. Large hydrophobic apoproteins (apo-B) bind irreversibly to the surface of CM, VLDL, and LDL, whereas smaller amphipathic apoproteins (apo-A, C, D, and E) are reversibly bound to the surface of the lipoprotein by hydrophobic a-helical domains of the apoprotein.

There is abundant evidence to support the concept that the outer layer of plasma lipoproteins is a monolayer of polar lipids (phospholipids, mainly phosphatidylcholine, and cholesterol) and apolipoproteins with the hydrophilic aspect of the apolipoproteins and the polar head groups of phospholipids on the surface. The evidence has been reviewed by others [e.g., (S24)] and will not further be examined here. Nuclear magnetic resonance studies on HDL have shown that about 40% of unesterified cholesterol molecules are in the lipoprotein core, and 60% are associated with phospholipid molecules in the surface. Neither surface nor core is saturated with cholesterol (L20). Presumably, unesterified cholesterol is also found in the core of other lipoproteins. 

Fig. 2. A model for lipoprotein structure based on the interactions between apolipopro-teins and lipid constituents. The surface monolayer is composed of phospholipids and apolipoproteins. The apoproteins contain helical regions which are amphipathic. The hydrophobic surface of the amphipathic helix interacts with the fatty acyl chains of phospholipids, and the hydrophilic surface is exposed to the aqueous environment of the polar head groups and the plasma. Adapted from Pownall et al.. (1981).

From this emulsion particle model, it was possible to predict the lipoprotein composition, buoyant density, and hydrodynamic properties of the LDL as a function of lipoprotein size, given the partial specific volumes of the lipid, protein, and carbohydrate components. A cross-sectional slice through the model is shown in Fig. 3 as two concentric circles, representing the hydrophobic core surrounded by a monolayer of phospholipid, cholesterol, and protein. The model parameters are given in the footnote to Table II and include the thickness of the shell, the... 

For simplicity of calculation, the core was assumed to contain all of the triglyceride and cholesteryl ester, although it is known that small amounts of the core lipids are dissolved in the surface monolayer, where they represent about 3 mol% of the surface lipids, and a larger fraction, about one ninth of the cholesterol, is dissolved in the core (Miller and Small, 1987). The presence of core lipids in the lipoprotein surface is very important metabolically, for the lipases and transfer proteins have access to these core lipids without having to penetrate the surface monolayer. For the calculation of composition, density, and size, however, the effects of component transfer between surface and core affect these quantities about one part in the fourth significant figure, and have been neglected in Table II. 

Fig. 1. General oil-droplet model of lipoproteins is presented for chylomicron, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) structures. Apolipoproteins in the outer phospholipid membrane, designated by letters, are defined in Table II. The major differences between the lipoproteins are the size of the neutral lipid (triglyceride and esterified cholesterol) core, liquid composition in the core, and apolipoprotein composition. (E) Triglycerides, ( Q ) phospholipids, and ( -) esterified cholesterol are shown. Although not shown, unesterified cholesterol is found predominantly in the phospholipid monolayer.

Cholesterol and triacylglycerides (TAGs) are transported as complexes in the form of lipoprotein particles. These lipoprotein particles contain a core of TAGs and cholesteryl esters surrounded by a monolayer of phospholipids, cholesterol, and specific proteins called apoproteins. The apoproteins, specific to each type of lipoprotein, enable the hydrophobic lipids to be transported in the aqueous environment of the bloodstream. They also contain signals that target the lipoprotein particles to the cells or activate enzymes. The lipoprotein particles vary in density depending on the lipid/protein ratio and are named based on these densities. The higher the lipid/protein ratio, the lower the density of the particle. 

Lipoproteins vary in diameter from 5 to 1000 nm. Each type of lipoprotein contains a neutral lipid core composed of cholesteryl esters and/or triacylglycerols. This core is surrounded by a layer of phospholipid, cholesterol, and protein. Charged and polar residues on the surface of a lipoprotein enable it to dissolve in blood. In LDL (low-density lipoprotein), the example illustrated in this figure, each particle is composed of a core of cholesteryl esters surrounded by a monolayer that consists of hundreds of cholesterol and phospholipid molecules and one molecule of apolipoprotein B-100. 

Cholesterol, which is largely insoluble in aqueous m a, travels through the blood circulation in the form of Upoprotein complexes. The plasma lipoproteins are a family of globular particles that share common structural features. A core of hydrophobic lipid, principally triacylglycerols (triglycerides) and cholesterol esters, is surrounded by a hydrophilic monolayer of phospholipid and protein (the apolipoproteins) [1-3]. Lipid-apolipoprotein interactions, facihtated byi amphi-pathic protein helices that segregate polar from nonpolar surfaces [2,3], provide the mechanism by which cholesterol can circulate in a soluble form. In addition, the apolipoproteins modulate the activities of certain enzymes involved in Upoprotein metabolism and interact with specific cell surface receptors which take up Upopro-teins by receptor-mediated endocytosis. Differences in the Upid and apoUpoprotein compositions of plasma Upoproteins determine their target sites and classification based on buoyant density. 

A lipoprotein particle has a shell composed of proteins (apolipoproteins) and a cholesterol-containing phospholipid monolayer (Figure 18-12). The shell is amphipathic because its outer surface is hydrophilic, making these particles water soluble, and its inner surface is hydrophobic. Adjacent to the hydrophobic inner surface of the shell is a core of neutral lipids containing mostly cholesteryl esters, triglycerides, or both. Small amounts of other hydrophobic compounds (e.g., vitamin E, carotene) also are carried in the lipoprotein core. 

A FIGURE 18-12 Model of low-density lipoprotein (LDL). This class and the other classes of lipoproteins have the same general structure an amphipathic shell, composed of a phospholipid monolayer (not bilayer), cholesterol, and protein, and a hydrophobic core, composed mostly of cholesteryl esters or triglycerides or both but with minor amounts of other neutral lipids (e.g., some vitamins). This model of LDL is based on electron microscopy and other low-resolution biophysical methods. LDL is unique in that it contains only a single molecule of one type of apolipoprotein (apoB), which appears to wrap around the outside of the particle as a band of protein. The other lipoproteins contain multiple apolipoprotein molecules, often of different types. [Adapted from M. Krieger, 1995, in E. Haber, ed., Molecular Cardiovascular Medicine, Scientific American Medicine, pp. 31-47]... 

Lipoproteins are large particles with cores of neutral lipids (cholesteryl esters, triglycerides) and amphipathic shells composed of apollpoprotelns, a monolayer of phospholipids, and unesterified cholesterol. 

The triacylglycerol (TG)-rich lipoproteins (very low density lipoproteins (VLDLs) and chylomicrons (CM)) are secreted into the circulation by hepatocytes of the liver and ente-rocytes of the intestine. All plasma lipoproteins share a common structure with a neutral lipid core, consisting of TGs and cholesteryl esters, surrounded by a surface monolayer of... 

Each newly synthesized intestinal apo B-containing lipoprotein particle (chylomicron) consists of a core lipid droplet rich in TG, surrounded by a monolayer made up mainly of protein, phospholipids, and cholesterol. The chylomicron lipid core contains a small amount of CE. The lipids of TG-rich particles are in a dynamic equilibrium where each lipid can exchange rapidly between the surface and core. As a result, while the great majority of TG is in the core, the surface contains a small but rapidly replenished pool ofTG which is the direct substrate of the plasma lipases responsible for chylomicron metabolism in the circulation. 

Phospholipids comprise the outer monolayer of lesional lipoproteins and the membranes of lesional cells. In lipoproteins, the phospholipid monolayer provides an amphipathic interface between the neutral lipid core and the aqueous external environment, and provides the structural foundation for the various apolipoproteins (Chapter 18). In the specific context of atherosclerosis, the phospholipids of lesional lipoproteins are modified by various oxidative reactions that could have important pathological consequences. In lesional cells, membrane phospholipids not only play structural roles but also are precursors to important phospholipase-generated signaling molecules that may participate in atherogenesis. 

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