High-density lipoproteins core lipids

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. 

Apolipoproteins ( apo designates the protein in its lipid-free form) combine with lipids to form several classes of lipoprotein particles, spherical complexes with hydrophobic lipids in the core and hydrophilic amino acid side chains at the surface (Fig. 21-39a). Different combinations of lipids and proteins produce particles of different densities, ranging from chylomicrons to high-density lipoproteins. These particles can be separated by ultracentrifugation (Table 21-2) and visualized by electron microscopy (Fig. 21-39b). 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Lipoproteins are globular, micelle-like particles consisting of a hydrophobic core of triacylglycerols and cholesterol esters surrounded by an amphipathic coat of protein, phospholipid and cholesterol. The apolipoproteins (apoproteins) on the surface of the lipoproteins help to solubilize the lipids and target the lipoproteins to the correct tissues. There are five different types of lipoprotein, classified according to their functional and physical properties chylomicrons, very low density lipoproteins (VLDLs), intermediate density lipoproteins (IDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs). The major function of lipoproteins is to transport triacylglycerols, cholesterol and phospholipids around the body. 

Cholesterol and triacylglycerols are transported in body fluids in the form of lipoprotein particles. Each particle consists of a core of hydrophobic lipids surrounded by a shell of more polar lipids and apoproteins. The protein components of these macromolecular aggregates have two roles they solubilize hydrophobic lipids and contain cell-targeting signals. Lipoprotein particles are classified according to increasing density (Table 26.1) chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Ten principal apoproteins have been isolated and characterized. They are synthesized and secreted by the liver and the intestine. 

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.

Lipoproteins are often called pseudomicellar because their outer shell is in part composed of amphipathic phospholipid molecules. Unlike simple micelles, lipoproteins contain apolipoproteins, or apoproteins, in their outer shell and a hydrophobic core of triacylglycerol and cholesteryl esters. Unesterified, or free, cholesterol, which contains a polar group, can be found as a surface component and in the region between the core and surface (Figure 20-1). Most lipoproteins are spherical. However, newly secreted high-density lipoproteins (HDLs) from the liver or intestine are discoidal and require the action of lecithin-cholesterol acyltransferase (LCAT) in plasma to expand their core of neutral lipid and become spherical. The hydrophobic core of the low-density lipoprotein (LDL) molecule may contain two concentric layers one of triacylglycerol and another of cholesteryl ester. 

The cholesterol esterification reaction is thought to occur primarily on the surface of high-density lipoproteins (HDL) where both of the lipid substrates and one or more apohpoprotein activators are located (Fig. 2A). The enzyme presumably binds transiently to the same surface, and catalyzes the transfer of a fatty acyl group mainly from the C-2 position of PC to the S S-hydroxyl group of UC. Because linoleic acid, arachidonic acid, and oleic acid usually predominate in the C-2 position, the CE formed are rich in these fatty acids. Once formed, the CE for the most part leave the lipoprotein surface. They partition into the core of the HDL or are transferred to other lipoproteins by the plasma CETP (see later). Meanwhile, the lysoPC formed by the LCAT reaction equilibrates with other lipoproteins and particularly with albumin. These changes in distribution of CE and lysoPC presumably account for the fact that the reaction is essentially irreversible. 

Lipoprotein complexes usually have a lipid core surrounded by one or more apolipoprotein molecules. These complexes can be separated into classes according to density. They range from very low density lipoproteins (VLDL), having densities of less than 1.006 g/mL, to low density lipoproteins (LDL), having densities of between 1.019 and 1.063 g/mL, to high density lipoproteins (HDL), having densities of between 1.063 and 1.210... 

A specific type of interaction between lipids and proteins is found in lipoproteins which transport triglycerides and cholesteryl esters in the plasma of mammalians. The largest lipoproteins, chylomicrons with a diameter between 800 A and 5000 A, and very-low-density lipoproteins (VLDL), with a diameter of 300-800 A, resemble emulsion droplets with a core of non-polar lipid and a surface coat of phospholipids and proteins (cf. Brown et ai, 1981). A physical characterization of chylomicrons has been reported (Parks et al.y 1981). Most of the plasma cholesterol occurs in low-density lipoprotein (LDL) which is a particle with a diameter of 200 A. The core consists of almost pure cholesteryl esters and a surface coat of a phospholipid monolayer and four tetrahedrally arranged apoproteins (Gulik-Krzywicki et aly 1979). The smallest particle, high-density lipoprotein (HDL), is a kind of molecular lipid-protein complex. 

Figure 37.4 Lipoproteins. Lipoproteins are macromolecular complexes used by the body to transport lipids in the blood. They are characterised by an outer coat of phospholipids and proteins, which encloses an inner core of hydrophobic TAG and cholesteryl ester. Lipoproteins tire classified according to the way they behave on centrifugation. This in turn corresponds to their relative densities, which depends on the proportion of (high density) protein to (low density) lipid in their structure. For example, high density lipoproteins (HDLs) consist of 50% protein and have the highest density, while chylomicrons (1% protein) tmd very low density lipoproteins (VLDLs) have the lowest density.

Plasma lipoproteins (LPs) are soluble aggregates of lipids and proteins that deliver hydrophobic, water-insoluble lipids (triglycerides and cholesteryl esters) from the liver and intestine to other tissues in the body for storage or utilization as an energy source [60]. All LP particles have a common structure of a neutral lipid core surrounded by a surface monolayer of amphipathic lipids (phospholipids and unesterified cholesterol) and some specific apoproteins (Fig. 14). The LPs are usually classified according to density, from very low-density lipoprotein (VLDL) to high-density lipoprotein (HDL). The size of LPs varies from 5-12 nm for HDL to 30-80 nm for VLDL. 

Fat, including cholesterol, absorbed from the diet is insoluble in the water-based medium of the blood. To enable transport through the blood system, the various fat components are incorporated into particles called lipoproteins (for reviews on lipoprotein metabolism, see Grundy, 1983 Mahley and Innerarity, 1983). Lipoproteins consist of a lipid core of triglyceride and cholesterol ester with a surface of mainly phospholipid and protein (referred to as apolipoprotein), plus some free cholesterol. The different apolipoproteins present function to regulate lipoprotein metabolism (for review on apolipoproteins, see Mahley et al., 1984). The cholesterol in lipoproteins is mainly transported as cholesterol ester. There are four main lipoprotein fractions found in the blood chylomicrons, very-low density lipoprotein (VLDL), low density Upopro-tein (LDL), and high density lipoprotein (HDL). 

---