Phospholipids lipoproteins

Cholesterol-phospholipid-lipoprotein liquid crystal phase, 15 112 Cholestyramine, 14 420... 

Lipopolysaccharide WallTeichoic Acid Lipoteichoic Acid -Outer Membrane Phospholipid Lipoprotein Peptidoglycan... 

The cells of Gram-positive bacteria have an outer covering or membrane containing teichoic acids, whereas the walls of Gram-negative bacteria are covered with a smooth, soft lipopolysaccharide which also contains phospholipids, lipoproteins, and proteins. This layer acts a barrier and penicillins have to negotiate a limited number of protein channels in order to reach the cell. 

Lipids are a diverse group of biomolecules that dissolve in nonpolar solvents. They can be separated into the following classes fatty acids and their derivatives, triacylglycerols, wax esters, phospholipids, lipoproteins, sphingolipids, and the isoprenoids. 

Kiechl, S. et al. Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase A2 activity, and 10-year cardiovascular outcomes prospective results from the Bru-neck study. Arterioscler. Thromb. Vase. Biol. 27 (2007) 1788-95. 

Fefer P, Tsimikas S, Segev A et al. The role of oxidized phospholipids, lipoprotein (a) and biomarkers of oxidized lipoproteins in chronically occluded coronary arteries in sudden cardiac death and following successful percutaneous revascularization. 

The type of fatty substances which are most commonly found In the blood are triglycerides, fatty acids, cholesterol, phospholipids, lipoproteins, and the fat-soluble vitamins A, D, E, and K. 

Other Lipids. Other important lipids include primarily the phospholipids, lipoproteins, and cholesterol. All cells contain phospholipids. They are structural compounds found in cell membranes and in the blood. The brain, nerves, and liver contain particularly high levels. Lecithin is one of the most abundant phospholipids in the diet and the body. Phospholipids are powerful emulsifying agents. Lipoproteins are the primary vehicle for lipid transport in the blood. There are four main types chylomicrons very low density lipoproteins (VLDL) low density lipoproteins (LDL) and high density lipoproteins (HDL). Cholesterol is derived from the dietorsyn e-sized in the body. It is necessary for the formation of hormones and bile salts. These will all be discussed in sections which follow. 

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

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

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

Plasma lipid transfer proteins, which include the cholesteryl-ester-transfer-protein (CETP previously known as lipid transfer protein I, LTP-I) and the phospholipid-transfer-protein (PLTP previously known as lipid transfer protein II, LTP-II) mediate the transfer of lipids (cholesteryl esters, triglycerides and phospholipids) between lipoproteins present in human plasma. These proteins significantly affect plasma lipoprotein concentration and composition. 

The main transport form of lipids in the cir culation. They are spherical macromolecules of 10-1200 nm diameter-composed of a core of neutral lipids (mostly cholesterol ester and triglycerides) surrounded by an amphipathic shell of polar phospholipids and cholesterol. Embedded in the shell of lipoproteins are apolipoproteins that are essential for assembly of theparticles in tissues that secrete lipoproteins, and for their recognition by target cells. 

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.

The second type of fatty liver is usually due to a metabolic block in the production of plasma lipoproteins, thus allowing triacylglycerol to accumulate. Theoretically, the lesion may be due to (1) a block in apolipoprotein synthesis, (2) a block in the synthesis of the lipoprotein from lipid and apolipoprotein, (3) a failure in provision of phospholipids that are found in lipoproteins, or (4) a failure in the secretory mechanism itself. 

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 Gram-negative cell envelope (Fig. 1.4) is even more complicated essentially, it contains lipoprotein molecules attached covalently to the oligosaccharide backbone and in addition, on its outer side, a layer of lipopolysaccharide (LPS) and protein attached by hydrophobic interactions and divalent metal cations, Ca and Mg. On the inner side is a layer of phospholipid (PL). 

Steinbrecher, U.P., Parthasarathy, S., Leake, D.S., Witztum, J.L. and Steinberg, D. (1984). Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc. Natl Acad. Sci. USA 81, 3883-3887. 

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