Cholesterol, plasma lipoproteins, association with

Nasta et al. also tried to investigate the relationship between cholesterol and mood states in the initial puerperal period. Their results showed that reduced plasma cholesterol concentration was associated with major feelings of fatigue and depressed mood [79]. In addition, West et al. compared the effects of transdermal versus oral estrogens on the vascular resistance index, mean arterial pressure, serum lipid concentrations, norepinephrine, and left ventricular structure in 10 postmenopausal women. The results showed that oral and transdermal estrogen significantly decreased the vascular resistance index, mean arterial pressure, norepinephrine, and total and low-density lipoprotein cholesterol to a similar extent [80],... 

Couture P, Otvos JD, Cupples LA, Wilson PW, Schaefer EJ, Ordovas JM. Association of the A-204C polymorphism in the cholesterol 7alpha-hydroxylase gene with variations in plasma low density lipoprotein cholesterol levels in the Framingham Offspring Study. J lipid Res 1999 40 1883-1889. 

Guerra R, Wang J, Grundy SM, Cohen JC. A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol. Proc Natl Acad Sci USA 1997 94 4532-4537. 

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. 

Most plasma cholesterol is in an esterified form (with a fatty add attached at C-3, see Figure 18.2), which makes the structure sen more hydrophobic than free cholesterol. Cholesteryl esters are rot found in membranes, and are normally present only in low levels in most cells. Because of their hydrophobicity, cholesterol and ils esters must be transported in association with protein as a compo nent of a lipoprotein particle (see p. 225) or be solubilized by phos pholipids and bile salts in the bile (see p. 223). 

Unlike other lipoproteins, HDL particles are assembled outside of cells from lipids and proteins, some of which may be donated from chylomicrons (see Fig. 21-1) or other lipoprotein particles. HDL has a higher protein content than other lipoproteins and is more heterogeneous. The major HDL protein is apolipoprotein A-I, but many HDL particles also contain A-jj 205,208-210 ancj apolipoproteins A-IV, D, and E may also be present. A low plasma level of HDL cholesterol is associated with a high risk of atherosclerosis.205 207... 

Until 1993 apolipoprotein E was best known for its central role in plasma lipoproteins and cholesterol transport (Fig. 21-1). However, one of the three common alleles of the apoE gene confers a significant risk of development of Alzheimer disease.12171218 A high blood cholesterol level is also correlated with increased risk.12191220 Membrane abnormalities in mitochondria have been associated with Alzheimer disease.1221 Also related to membranes and lipid metabolism, vitamin E appears to combat Alzheimer disease.843 1218... 

The structures of the various lipoproteins appear to be similar (figs. 20.11 and 20.12). Each of the lipoprotein classes contains a neutral lipid core composed of triacylglycerol and/or cholesteryl ester. Around this core is a coat of protein, phospholipid, and cholesterol, with the polar portions oriented toward the surface of the lipoprotein and the hydro-phobic parts associated with the neutral lipid core. The hydrophilic surface interacts with water in plasma, promoting the solubility of the lipoprotein. 

In this chapter we dealt primarily with the metabolism of cholesterol, the most prominent member of the steroid family of lipids, and with the associated plasma lipoproteins. The chief points in our discussion are as follows ... 

The general structure of lipoproteins is shown schematically in Figure 3. The core of the lipoprotein contains the more hydrophobic lipids namely cholesterol ester (CE) and triglyceride (TG) and is surrounded by a surface monolayer consisting of the more polar phospholipid (PL) and free cholesterol (FC). Apoproteins are associated with the lipoprotein surface. The proportional composition of human plasma lipoproteins is given in Table 7. 

There is abundant evidence to support the concept that the outer layer of plasma lipoproteins is a monolayer of polar lipids (phospholipids, mainly phosphatidylcholine, and cholesterol) and apolipoproteins with the hydrophilic aspect of the apolipoproteins and the polar head groups of phospholipids on the surface. The evidence has been reviewed by others [e.g., (S24)] and will not further be examined here. Nuclear magnetic resonance studies on HDL have shown that about 40% of unesterified cholesterol molecules are in the lipoprotein core, and 60% are associated with phospholipid molecules in the surface. Neither surface nor core is saturated with cholesterol (L20). Presumably, unesterified cholesterol is also found in the core of other lipoproteins. 

The rate of cholesterol esterification in plasma is not correlated with HDL concentration (A12, R17, S45, S58, Wl, W2) but is correlated with the concentration of VLDL or triglyceride (A12, P8, R17, S58, T7, Wl, W2). Although HDL is the major substrate for LCAT, VLDL and indirectly LDL are the major recipients of the esterfied cholesterol, transferred (it is thought) by lipid transfer protein. Accumulation of esterified cholesterol in the recipient lipoproteins is associated with a decrease in LCAT activity (C7, Fll, F13) that can be relieved by the addition of recipient lipoproteins but not by addition of LCAT substrate (Fll). Hopkins and Barter (H32, H33) have explained these observations by showing that the depletion of HDL esterified cholesterol by transfer to VLDL enhances the capacity of HDL to act as a substrate for LCAT. 

P13. Pinon, J. C., Bridoux, A. M., and Laudat, M. H., Initial rate of cholesterol esterification associated with high density lipoproteins in human plasma. /. Lipid Res. 21, 406-414 (1980). 

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