Lipids apolipoprotein complexes

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. 

Although PL liposomes are favored systems for the study of apolipoprotein binding to PL surfaces, vesicle-apolipoprotein complexes are not the ideal models for lipoproteins. Vesicles have an interior water compartment not present in lipoproteins, are incapable of solubilizing large amounts of neutral lipids within the PL bilayer, and are too large to mimic the surface curvature of HDL. Thus, methods have been developed to prepare small, micellar complexes of exchangeable apolipoproteins (in particular apo Al) with lipids that mimic discoidal and spherical HDL in shape, composition, and functional properties. For LDL and VLDL, microemulsions and emulsions of lipids of selected diameter and composition, with added apo B 100, make good models of the native lipoproteins. 

Lipids are nonpolar molecules and are relatively insoluble in aqueous solutions. At low concentrations, cholesterol and cholesterol esters, as well as other lipids, may form microscopic droplets called chylomicrons (lipid-protein complexes) that are somewhat stable in solution. At high concentrations, the lipids would form larger droplets and clog blood vessels, so they must be transported as complexes of lipid and protein called lipoproteins. Lipoproteins are complexes of lipid and precursor protein molecules called apolipoproteins. 

Because of their relatively large hydrophobic surface area, apolipoproteins, in the absence of lipids, readily self-associate in aqueous solution (Stone and Reynolds, 1975 Vitello and Scanu, 1976). The rate of desorption of apolipoproteins from lipoprotein surfaces has not been studied systematically. Extensive studies of the reverse process, which is the assembly of lipid apoprotein complexes, have been conducted in considerable detail. The dynamic of lipid-protein interactions have been studied primarily with in vitro model systems. Analysis of the association of apolipoproteins with various phospholipid aggregates have provided important clues about the nature of the kinetically important steps in the transfer of apolipoproteins between lipoproteins (Pownall et al., 1977 1978a Massey et al., 1981a Mantulin et al., 1981). 

The protein moieties of lipoproteins fulfil two main functions firstly, they provide a means of solubilizing the lipid particles and maintaining their structural integrity (section 5.3.5(k)). Secondly, they are important in identifying the lipoprotein and directing its metabolism in specific ways. The main metabolic functions of the apolipoproteins are shown in Table 5.11. The term apoprotein was first used in 1963 to describe the protein moiety of a number of delipidated lipid—protein complexes and the more specific term apolipoprotein will be used here. It has now become accepted to use a series of letters A-E to identify apolipoproteins but it soon became apparent that most of these could be divided further into several sub-classes (Table 5.11). These are usually referred to in abbreviated form, thus apoAi, apoCs, etc. 

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 are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

Free fatty acids are transported as complexes with serum albumin. Cholesterol, triacylglycerols, and phospholipids are transported as protein-lipid complexes called lipoproteins. Lipoproteins are spherical, with varying amounts and kinds of proteins at their surfaces. The protein components, of which at least ten exist, are called apolipoproteins. Lipoproteins are classified in terms of their density. 

Hydrophobic lipids (triacylglycerols and cholesteryl esters) are virtually completely insoluble in water they are solubilized for transport in plasma by incorporation into lipoproteins. Lipoproteins are spherical complexes containing triacylglycerol (triglyceride) and cholesteryl ester surrounded by a layer containing phospholipids, unesterified cholesterol, and specific apolipoproteins. 

These proteins are of great interest because of their relationship to coronary heart disease (CHD). Lipoproteins, a group of macromicellar complexes of lipids and proteins, are closely associated with the risk of developing CHD. Structurally, lipoprotein particles contain a nonpolar lipid core of triglycerides and cholesterol esters and a polar surface that is comprised of apolipoproteins and unesterified cholesterol and phospholipids. There are three principle classes of lipoproteins ... 

The crystal structure of L. migratoria apoLp-III was obtained for the protein in its lipid-free state. The lipid-bound structure of apoLp-III, however, is more interesting since it represents the active form of the protein. To date, no detailed structural reports for exchangeable apolipoproteins in complex with lipid have been reported. The crystal structure of lipid-free apoLp-III demonstrated that the five amphipathic helices orient in such a way that their hydrophobic faces are directed toward each other to form a hydrophobic core while the hydrophilic faces of the helices are exposed to solvent. It has been hypothesized that, upon binding to a... 

The lipids of the diet include TGs, phospholipids, cholesteryl esters, cholesterol, and the fat-scivble vitamins. These nutrients require special types of biochemical machinery to facilitate their assimilation and distributicrt within the body. The biochemical apparatus used includes bile salts, apolipoprotcins, serum albumin, and vitamin-binding proteins. Apolipopnoteins are the primary subject of this section. The term apolipoprotain is used when referrmg only to the protein, whereas the term lipoprotein refers to the complex of apolipoprotein and lipid. 

These results show two distinct features of lipophorin biosynthesis during the larval stage. First, the nascent lipophorin produced in the fat body by de novo synthesis is an apolipoprotein-phospholipid complex that derives its transported lipids from the midgut. Second, lipophorin biosynthesis is not coupled to fat intake, as is the case with vertebrates. These processes are illustrated in Fig. 6 and fit observations made on lipid storage in larvae. Thus, it has been shown that more than 70% of the fatty acids in the diet are stored as TG in the larval fat body (Tsuchida and Wells, 1988). Although the fat body can convert carbohydrates to fatty... 

Unlike other plasma proteins, such as transferrin and prealbumin, apolipoproteins circulate in the bloodstream as part of the lipoprotein complex. As discussed earlier, lipoprotein particles are heterogenous spheres consisting of lipids and... 

Plasma contains several apolipoproteins, involved in lipid and cholesterol transport. Several have been reported to be glycosylated in low amounts including apoB, apoE and apoC-llI [26]. ApoB contains about 2-2.5% carbohydrate as complex-type N-glycan whereas apoE appears to contain O-linked glycan [27]. ApoE is synthesized in sialylated form but in plasma it is 80% desialylated. 

Although the term lipoprotein can describe any protein that is covalently linked to lipid groups (e.g., fatty acids or prenyl groups), it is most often used for a group of molecular complexes found in the blood plasma of mammals (especially humans). Plasma lipoproteins transport lipid molecules (triacylglycerols, phospholipids, and cholesterol) through the bloodstream from one organ to another. Lipoproteins also contain several types of lipid-soluble antioxidant molecules (e.g., a-tocopherol and several carotenoids). (The function of antioxidants, substances that protect biomolecules from free radicals, is described in Chapter 10.) The protein components of lipoproteins are called apolipoproteins or apoproteins. 

Lipoproteins are soluble complexes of proteins (apolipoproteins) and lipids that transport lipids in the circulation of all vertebrates and even insects. Lipoproteins are synthesized in the liver and the intestines, arise from metabolic changes of precursor lipoproteins, or are assembled at the cell membranes from cellular lipids and exogenous lipoproteins or apolipoproteins. In the circulation, lipoproteins are highly dynamic. They undergo enzymatic reactions of their lipid components, facilitated and spontaneous lipid transfers, transfers of soluble apolipoproteins, and conformational changes of the apolipoproteins in response to the compositional changes. Finally, lipoproteins are taken up and catabolized in the liver, kidney, and peripheral tissues via receptor-mediated endocytosis and other mechanisms. This chapter deals with the composition and structure of human lipoproteins. 

Several methods are known for the reconstitution of HDL-like complexes from pure components (i) spontaneous formation of HDL discs from dimyristoylphosphatidyl-choline liposomes (ii) detergent-mediated reconstitution of HDL discs with various PL and (iii) co-sonication of apolipoproteins and lipids to form either discoidal or spherical HDL analogs [19]. 

Intermediate-density lipoproteins and LDLs are generated in the circulation by lipolysis of TGs within CM and VLDLs (Chapter 19). Apo B is an essential component of CM, VLDLs, and LDLs. Unlike the exchangeable plasma apolipoproteins (apo E, apo Al, apo A2, and apo C), apo B does not exchange among lipoproteins and is present in plasma only in association with lipid. In addition to apo B, VLDLs and CM contain apo E and apo C CM contain small amounts of apo Al and apo A2. In contrast, apo B is the only apolipoprotein of LDLs. HDLs are particles of diverse composition that are generated in the circulation by complex lipid transport processes (Chapter 19). 

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