Low density lipoproteins phospholipids

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. 

Bird DA, LaposataM, Hamilton J A. Binding of ethyl oleate to low density lipoprotein phospholipid vesicles, and albumin A NMR study. J Lipid Res 1996 37 1449-1458. 

Low density lipoprotein (LDL) (/3-lipoprotein) Triacylglycerols, phospholipids, cholesterol 67... 

Figure 25-4. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL). (A, apolipoprotein A B-100, apolipoprotein B-100 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylglycerol IDL, intermediate-density lipoprotein C, cholesterol and cholesteryl ester P, phospholipid.) Only the predominant lipids are shown. It is possible that some IDL is also metabolized via the LRP.

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.

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. 

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... 

Boullier, A., GUlotte, K.L., Horkko, S., Green, S.R., Friedman, P., Dennis, E.A., Witzmm, J.L., Steinberg, D., and Quehenberger, O., 2000, The binding of oxidized low density lipoprotein to mouse CD36 in mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the hpoprotein, J. Biol. Chem. 275 9163-9169. 

Most of the mention of cholesterol in the popular press positions this molecule as a threat to human health. Many foods are proudly labeled cholesterol-free. People are properly warned to pay attention to their plasma cholesterol level, particnlarly that carried in the low-density lipoproteins, LDLs, commonly known, with pretty good reason, as bad cholesterol. LDLs are lipoprotein particles containing a large protein known as B-100 associated with cholesterol, cholesteryl esters, phospholipids, and some triglycerides. 

The resulting triacylglycerol is stored in adipose tissue. In the liver, some is combined with protein and phospholipids to form a complex, known as very low density lipoprotein (VLDL), which is secreted from the liver into the blood. Details of the formation of VLDL are presented in Appendix 11.2. Failure to form VLDL or secrete can cause accu-... 

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. 

Deoxycholic acid Arachadonic acid rich phospholipids Low density lipoproteins Transferring ... 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

High-density lipoproteins are formed in the liver and intestines as a result of catabolism of chylomicrons and very low-density lipoproteins, and in comparison with other lipoproteins, they contain considerably more cholesterol esters with unsaturated fatty acids, as well as phospholipids and specific proteins. 

The fatty acids could be carried by proteins by a process similar to the way in which serum albumin binds fatty acid in the bloodstream of mammals. Other types of lipid might be formed into complexes analogous to low-density lipoproteins of the type found in animal tissues, where the lipid core of the lipoprotein is surrounded by a hydrophilic cortex made up of protein, phospholipid, and cholesterol (87). This allows the lipid to be moved in an aqueous environment. The protein of the lipoprotein shell could also act as possible ligands for particular receptors at the membrane of the cell at which the export occurs. The lipoproteins, if they are present, would probably be formed within the endomembrane lumen and would receive the proteins at the endoplasmic reticulum. 

Spin trapping has also been applied to the investigation of lipid peroxidation catalysed by myoglobin in linoleate emulsions,204 as well as the oxidation of phospholipids in low-density lipoproteins (18.1) by HOC1.205 Hiramoto et al. have shown that, by quenching the attacking radicals, linoleic acid can protect DNA from oxidation.206 Lipid peroxidation has also been monitored by spin labelling.207... 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

In adipose tissue, TAG is stored in the cytosol of the cells in a nearly anhydrous form. It serves as "depot fat," ready for mobilization when the body requires it for fuel. Little TAG is stored in the liver. Instead, most is exported, packaged with cholesteryl esters, cholesterol, phospholipid, and protein (apolipoprotein B-100, see p. 229) to form lipoprotein particles called very low density lipoproteins (VLDL). Nascent VLDL are secreted into the blood where they mature and function to deliver the endogenously-derived lipids to the peripheral tissues. [Note Recall that chylomicrons deliver primarily dietary (exogenously-derived) lipids.] Plasma lipoproteins are discussed in Chapter 18, p. 225. 

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... 

Synthesis of lipids from carbohydrates is an efficient process, which occurs largely in the liver and also in intestinal epithelial cells.6 The newly synthesized triacylglycerols, together with smaller amounts of phospholipids and cholesterol, combine with specific apolipoproteins, which are also synthesized in the liver, to form very low density lipoprotein (VLDL) particles which are secreted into the blood stream. 

Figure 21-1 Movement of triacylglycerols from liver and intestine to body cells and lipid carriers of blood. VLDL very low density lipoprotein which contains triacylglycerols, phospholipids, cholesterol, and apolipoproteins B, and C. IDL intermediate density lipoproteins found in human plasma. LDL low density lipoproteins which have lost most of their triacylglycerols. ApoB-100, etc., are apolipoproteins listed in Table 21-2. LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein (see Chapter 22).

Serum cholesterol. Most cholesterol is carried in the blood by low density lipoprotein (LDL, Tables 21-1,21-2), which delivers the cholesteryl esters directly to cells that need cholesterol. Both a 74-kDa cholesteryl ester transfer protein193-1953 and a phospholipid transfer protein196 1963 are also involved in this process. Cholesterol esterases, which release free cholesterol, may act both on lipoproteins and on pancreatic secretions.197-199... 

Leitinger N., Watson A. D., Faull K. F., Fogelman A. M., and Berliner J. A. (1997). Monocyte binding to endothelial cells induced by oxidized phospholipids present in minimally oxidized low density lipoprotein is inhibited by a platelet activating factor receptor antagonist. Adv. Exp. Med. Biol. 433 379-382. 

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