HDL phospholipids

High density lipoprotein (HDL) (a-lipoprotein) Triacylglycerols, phospholipids, cholesterol 75... 

Endothelial-anchored enzyme in multiple tissues primarily responsible for hydrolysis of phospholipids in HDL. 

Endothelial-anchored enzyme in liver primarily responsible for hydrolysis of triglycerides and phospholipids in Intermediate Density Lipoproteins (IDL) and High Density Lipoproteins (HDL). 

PLTP is responsible for the majority of phospholipid transfer activity in human plasma. Specifically, it transfers surface phospholipids from VLDL to HDL upon lipolysis of triglycerides present in VLDL. The exact mechanism by which PLTP exerts its activity is yet unknown. The best indications for an important role in lipid metabolism have been gained from knockout experiments in mice, which show severe reduction of plasma levels of HDL-C and apoA-I. This is most likely the result of increased catabolism of HDL particles that are small in size as a result of phospholipid depletion. In addition to the maintenance of normal plasma HDL-C and apoA-I concentration, PLTP is also involved in a process called HDL conversion. Shortly summarized, this cascade of processes leads to fusion of HDL... 

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure 25-1). These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane (Chapter 14). The protein moiety of a lipoprotein is known as an apo-lipoprotein or apoprotein, constituting nearly 70% of some HDL and as litde as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other hpoproteins. 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Figure 26-5. Factors affecting cholesterol balance at the cellular level. Reverse cholesterol transport may be initiated by pre 3 HDL binding to the ABC-1 transporter protein via apo A-l. Cholesterol is then moved out of the cell via the transporter, lipidating the HDL, and the larger particles then dissociate from the ABC-1 molecule. (C, cholesterol CE, cholesteryl ester PL, phospholipid ACAT, acyl-CoA cholesterol acyltransferase LCAT, lecithinicholesterol acyltransferase A-l, apolipoprotein A-l LDL, low-density lipoprotein VLDL, very low density lipoprotein.) LDL and HDL are not shown to scale.

The fate of injected liposomes is drastically altered by administration route, dose and size, lipid composition, surface modification, and encapsulated drugs. Liposomes encapsulating drugs are often administered iv, therefore, the stability of liposomes in plasma is important. When liposomes composed of PC with unsaturated fatty acyl chains are incubated in the presence of serum, an efflux of internal solute from the liposomes is observed. This increase in permeability is caused by the transfer of phospholipids to high density lipoprotein (HDL) in serum (55). To reduce the efflux of liposomal contents, cholesterol is added as a liposomal component... 

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. 

So far, we have focused mainly on the potential pathways of carotenoid uptake by the RPE from the choroidal blood supply. As mentioned earlier, POS contain lutein and zeaxanthin, and their distal tips are phagocytosed by the RPE. Therefore POS is another source of xanthophylls in the RPE and this pathway of carotenoid delivery and their further fate can be easily tested in cultured RPE. It has been shown that exposure of RPE cells in vitro to HDL stimulates efflux of phospholipids from phagocytosed POS out of the cell (Ishida et al., 2006). Thus it is of interest to determine whether that transport may potentially include xanthophylls and whether other types of lipoproteins may... 

Cholesterol, triglycerides, and phospholipids are transported in the bloodstream as complexes of lipid and proteins known as lipoproteins. Elevated total and LDL cholesterol and reduced HDL cholesterol are associated with the development of coronary heart disease (CHD). 

Many of the globulins act as transport proteins. Of particular interest are those proteins which are combined with lipids, themselves synthesized in the liver, to form lipoprotein complexes. High density lipoprotein (HDL), which contains predominantly apoproteins A and C combined with mainly phospholipids (most of the cholesterol found in mature HDL is added later) and very low density lipoprotein... 

Carrier of cholesterol and phospholipids (HDL) Protease inhibitor iosmotic regulator in fetus Unknown... 

Figure 11.15 The reaction catalysed by lecithin cholesterol acyltransferase (LCAT). LinoLeate is transferred from a phospholipid in the blood to cholesterol to form cholesteryl linoleate, catalysed by LCAT. The cholesterol ester forms the core of HDL, which transfers cholesterol to the liver. Discoidal HDL (i.e. HDL3) is secreted by the liver and collects cholesterol from the peripheral tissues, especially endothellial cells (see Figure 22.10). Cholesterol is then esterified with lin-oleic acid and HDL changes its structure (HDL2) to a more stable form as shown in the lower part of the figure. R is linoleate.

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. 

VLDLs, IDLs, and LDLs are closely related to one another. VLDLs formed in the liver (see p. 312) transport triacylglycerols, cholesterol, and phospholipids to other tissues. Like chylomicrons, they are gradually converted into IDL and LDL under the influence of lipoprotein lipase [1]. This process is also stimulated by HDL. Cells that have a demand for cholesterol bind LDL through an interaction between their LDL receptor and ApoB-100, and then take up the complete particle through receptor-mediated endocytosis. This type of transport is mediated by depressions in the membrane ( coated pits"), the interior of which is lined with the protein clathrin. After LDL binding, clathrin promotes invagination of the pits and pinching off of vesicles ( coated vesicles"). The clathrin then dissociates off and is reused. After fusion of the vesicle with ly-sosomes, the LDL particles are broken down (see p. 234), and cholesterol and other lipids are used by the cells. 

Apo A-I is the main structural apolipoprotein on HDL particles it is synthesized in hepatic and enteric cells. Bound phosphatidylcholine and sphingomyelin participate in the creation of protein-phospholipid complexes. 

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