Cholesterols in lipoproteins

Liver and some intestinal cells export cholesterol into the bloodstream, together with triacylglycerols and phospholipids in the form of VLDL particles, for uptake by other tissues (see Fig. 21-1). Cholesteryl esters are formed in the ER by lecithin cholesterol acyltransferase (LCAT), an enzyme that transfers the central acyl group from phosphatidylcholine to the hydroxyl group of cholesterol.191 1913 This enzyme is also secreted by the liver and acts on free cholesterol in lipoproteins.192 Tissue acyltransferases also form cholesteryl esters from fatty acyl-CoAs.192a... 

Fei H, Maeda S, Kirii H, Fujigaki S, Maekawa N, Fuji H, et al. Evaluation of two different homogeneous assays for LDL-cholesterol in lipoprotein-X-positive serum, CUn Chem 2000 46 1351-6. 

Cholesterol is obtained from the diet and synthesized in most cells of the body. It is a component of cell membranes and the precursor of steroid hormones and of the bile salts used for fat absorption. High concentrations of cholesterol in the blood, particularly the cholesterol in lipoprotein particles called low density lipoproteins (LDL), contribute to the formation of atherosclerotic plaques. These plaques (fatty deposits on arterial walls) are associated with heart attacks and strokes. A high content of saturated fat in the diet tends to increase circulatory levels of LDL cholesterol and contributes to the development of atherosclerosis. 

Table V. Twenty-Four-Hour Time-Averaged Mean (+SD) Plasma Total Cholesterol and Cholesterol in Lipoprotein Fractions of NIDDM Patients During LC and HL Profiles...

Fat, including cholesterol, absorbed from the diet is insoluble in the water-based medium of the blood. To enable transport through the blood system, the various fat components are incorporated into particles called lipoproteins (for reviews on lipoprotein metabolism, see Grundy, 1983 Mahley and Innerarity, 1983). Lipoproteins consist of a lipid core of triglyceride and cholesterol ester with a surface of mainly phospholipid and protein (referred to as apolipoprotein), plus some free cholesterol. The different apolipoproteins present function to regulate lipoprotein metabolism (for review on apolipoproteins, see Mahley et al., 1984). The cholesterol in lipoproteins is mainly transported as cholesterol ester. There are four main lipoprotein fractions found in the blood chylomicrons, very-low density lipoprotein (VLDL), low density Upopro-tein (LDL), and high density lipoprotein (HDL). 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

Defects in Lipoprotein Metabolism Can Lead to Elevated Serum Cholesterol... 

Cholesterol-rich lipoprotein particles that carry dietary lipids absorbed in the intestine and deliver them to the liver for uptake. 

Figure 2S-1. Generalized structure of a plasma lipoprotein. The similarities with the structure of the plasma membrane are to be noted. Small amounts of cholesteryl ester and triacylglycerol are to be found in the surface layer and a little free cholesterol in the core.

To control risk factors and prevent major adverse cardiac events, statin therapy should be considered in all patients with ischemic heart disease, particularly in those with elevated low-density lipoprotein cholesterol. In the absence of contraindications, angiotensin-converting enzyme inhibitors should be considered in ischemic heart disease patients who also have diabetes melli-tus, left ventricular dysfunction, history of myocardial infarction, or any combination of these. Angiotensin receptor blockers... 

Mensink, R. P., Katan, M. B., Effect of a diet enriched with monounsaturated or polyunsaturated fatty acids on levels of low-density and high-density lipoprotein cholesterol in healthy women, N Engl J Med, 321, 436, 1989... 

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. 

The liver plays a decisive role in the cholesterol metabolism. The liver accounts for 90% of the overall endogenic cholesterol and its esters the liver is also impli-cated in the biliary secretion of cholesterol and in the distribution of cholesterol among other organs, since the liver is responsible for the synthesis of apoproteins for pre-p-lipoproteins, a-lipoproteins, and P-lipoproteins which transport the secreted cholesterol in the blood. In part, cholesterol is decomposed by intestinal micro-flora however, its major part is reduced to coprostanol and cholestanol which, together with a small amount of nonconverted cholesterol, are excreted in the feces. 

Hyperlipoproteinemia, Type V. This pathology is manifested by increased con-tents of chylomicrons, pre-P-lipoproteins, triglycerides, and cholesterol in the patients blood plasma. 

Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

Apolipoprotein AIV (apo AIV) is produced in the intestine and is found in chylomicrons, VLDL and HDL. It may modulate enzymes involved in lipoprotein metabolism and may serve as a saturation signal [49]. In a study with 144 participants the apo AIV His360Glu polymorphism showed no significant effect on cholesterol lowering in response to statin therapy [50]. 

Monounsaturated fats in avocados have been shown to reduce blood cholesterol while preserving the level of high-density lipoproteins (Yahia 2009b). An avocado-enriched diet produced a significant reduction in LDL and total cholesterol in patients with high cholesterol levels, whereas diets enriched with soy and sunflower did not change the total cholesterol concentrations (Carranza and others 1997). 

The data obtained with SERMs are more mixed. Tamoxifen attenuated atheroma development in apoE-null mice, an effect that correlated with changes in the lipoprotein profile and with elevated levels of transforming growth factor-/ (Reckless et al. 1997). The accumulation of cholesterol in atherosclerotic lesions (Bjarnason et al. 1997) in the aorta was limited by... 

Chetty KN, Walker J, Brown K, et al. 1993a. The effects of dietary calcium and chlordecone on cholinesterase, triglycerides, low density lipoproteins, and cholesterol in serum of rat. Arch Environ Contam Toxicol 24 365-367. 

Ishikawa T, McNeeley S, Steiner PM, et al. 1978. Effects of chlorinated hydrocarbon on plasma alpha-lipoprotein cholesterol in rats. Metabolism 27(1) 89-96. 

E6. Eden, S., Wiklund, O., Oscarsson, J., Rosen, T., and Bengtsson, B. A., Growth hormone treatment of growth hormone deficient adults results in a marked increase in lipoprotein(a) and HDL-cholesterol concentration. Atheroscler. Thromb. 13, 296-301 (1993). 

Details of plasma lipoproteins and their metabolism are given in Section 5.5. Most of the cholesterol in the blood is carried as part of low density lipoprotein (LDL) or high density lipoprotein (HDL), whereas most triglyceride, in the fasting state, is carried by very low density lipoprotein (VLDL). The relative concentrations of these lipoproteins constitute the lipid profile and determine CVD risk. Diabetics are more likely to show an unhealthy profile with elevated concentrations of LDL and triglyceride but reduced HDL concentration. This pattern can be partly explained by enhanced fatty acid liberation from adipocytes as a consequence of insulin resistance in that tissue and due to reduced removal from the circulation of triglycerides, which is also insulin dependent. 

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