The Plasma Lipoproteins

LIPOPROTEINS. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index of susceptibility to vascular disease. 

The Plasma Lipoproteins James C. Osborne, Jr., and H. Bryan Brewer, Jr. 

Table 4. Most important lipid-lowering drugs available at present. An indication is given of the most relevant changes in the plasma lipoprotein fractions caused by these agents...

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). 

Composition of the plasma lipoproteins. Note high concentration of cholesterol and cholesteryl esters in LDL. 

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... 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They keep lipids (primarily, triacylglycerol and cholesteryl esters) soluble as they transport them in the plasma, and provide an efficient mechanism for transporting their lipid contents between tissues. 

Dietary cholesterol, together with triacylglycerols, is absorbed from the intestinal tract and enters the large lipoprotein chylomicrons (see Fig. 21-1). Absorption of cholesterol is incomplete, usually amounting to less than 40% of that in the diet. Absorption requires bile salts and is influenced by other factors.186 As it is needed cholesterol is taken from the plasma lipoproteins into cells by endocytosis. Much of the newly absorbed cholesterol is taken up by the liver. The liver also secretes cholesterol, in the form of esters with fatty acids, into the bloodstream. 

All of these biological roles of the steroids figure prominently in human well-being. Defects in cholesterol metabolism are major causes of cardiovascular disease. It is no wonder that steroids are a central concern in medical biochemistry. In this chapter we discuss the metabolism of these complex lipids and the plasma lipoproteins in which they and other complex lipids are transported to various tissues. 

The plasma lipoproteins are made mainly in the liver and intestine. In the rat, approximately 80% of the plasma apoproteins originate from the liver the rest are derived from the intestine. The components of chylomicrons, including apoproteins A-I, A-IV, and B-48 phospholipid cholesterol cholesteryl ester and triacylglycerols, are products of the intestinal cells. Chylomicrons are secreted into lymphatic capillaries, which eventually enter the bloodstream. The liver is the major source of VLDLs and HDLs. 

Relatively little is known about the possible interrelationships of the metabolism of the complex sugar-containing lipids, the glycosphingolipids (GSLs) and the plasma lipoproteins. 

Plasma Lipoproteins. The plasma lipids are transported by four major lipoprotein classes. The plasma lipoproteins are synthesized and secreted only in the intestine and liver. Chylomicrons, the richest in triglyceride, are synthesized in the small intestine and transport dietary (exogenous) triglyceride and cholesterol. Very low density (prebeta) lipoproteins (VLDL)... 

The plasma lipoproteins contain eight major apoproteins, the structure and function of which have recently been reviewed (5). Briefly, the primary amino acid sequence is known for five of these apoproteins. ApoB, a highly hydrophobic protein, is found in chylomicrons, VLDL and LDL. It is the major polypeptide in LDL and has been shown to be responsible, in part, for the recognition of LDL by its receptor in cultured human fibroblasts (7,10). The major polypeptides of HDL are apoA-I and apoA-II apoA-l activates lecithin cholesterol acyl transferase. In addition, studies on the cellular level suggest that apoA-I may regulate the content of the lipids in the cell membrane (8). 

H. Lithell, B. Odlind, I. Selinus, A. Lindberg, B. Lindstrom, and L. Frodin, Is the plasma lipoprotein pattern of importance for treatment with cyclosporine Transplant. Proc. 18 50-51 (1986). 

M16. Mahley, R. W., Weisgraber, K. H., and Innerarity, T. L., Canine lipoproteins and atherosclerosis. II. Characterization of the plasma lipoproteins associated with atherogenic and nonatherogenic hyperlipidemia. Circ. Res. 35, 722-733 (1974). 

Lock, A.L., Horne C.A.M., Bauman D.E., Salter A.M. 2005b. Butter naturally enriched in conjugated linoleic acid and vaccenic acid alters tissue fatty acids and improves the plasma lipoprotein profile in cholesterol-fed hamsters. J. Nutr. 135, 1934—1939. 

Which one of the following hyperlipidemias is characterized by elevated plasma levels of chylomicrons and has no drug therapy available to lower the plasma lipoprotein levels ... 

The different compositions of the plasma lipoproteins give a clue to their function. Essentially, those lipoproteins rich in TAGs are synthesized by the liver (VLDL) and small intestine (chylomicrons) and deliver the neutral fat to extrahepatic tissues (particularly adipose tissue). The fat-depleted lipoproteins have a higher density, and are involved in essential cholesterol transfers. 

Few investigators have examined hepatic lipid and lipoprotein production in response to exercise. Because nascent HDL are synthesized in the liver, intestine, and the plasma via the catabolism of triglyceride rich lipoproteins (52), exercise-induced modifications in any or all of these systems could lead to changes in the plasma lipoprotein profile. 

Modified (oxidized) lipid species have been identified in the plasma lipoproteins and aortic plaque of atherosclerotic humans (74, 77) and animal models (78, 79). Furthermore, the presence of COPs in circulating lipoprotein has been demonstrated in healthy humans (80) and monkeys. (73) Oxidized LDL has been proposed to have a role in foam cell formation (81) as well as having various proatherogenic properties, such as cytotoxicity and chemotactic activity (73, 82). 

LI. Lever, W. F., Smith, P. A. J., Hurley, N. A., Effect of intravenous heparin on the plasma lipoproteins in primary hypercholesteremic and idiopathic hyperlipemia. Science 118, 653-654 (1953). 

Devaraj, S. Vega-Lopez, S. Kaul, N. Schonlau, F. Rohdewald, P. Jialal, I. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids 2002,37(10), 931-934. 

The function of apoE in lipoprotein metabolism is reviewed in the sixth chapter by Karl Weisgraber. The three-dimensional structure of a 22-kDa fragment of human apoE (34.2 kDa) has been solved by X-ray crystallography the relation of this structure to the role of apoE in lipoprotein metabolism is discussed in detail, together with a critical and extensive examination of the chemistry and biology of this apolipoprotein which plays such a central role in lipoprotein metabolism. Apolipoprotein E has three major isoforms in the human population which affect lipoprotein metabolism differently, resulting in different levels of the plasma lipoproteins. The impact of structure on function and how plasma lipid concentrations are affected by the different apoE isoforms are the themes of this important chapter. 

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