Sources of cholesterol

The two significant sources of cholesterol in body are endogenously synthesized cholesterol and exogenous or dietary cholesterol. Efforts to inhibit the absorption of dietary cholesterol have primarily focused on the inhibition of ACAT, a major enzyme associated with cholesterol esterification. Inhibition of this enzyme blocks the absorption of intestinal cholesterol and may also inhibit cholesteryl ester deposition in the vascular wall in the form of fatty streaks associated with atherosclerotic plaque. 

Cholesterol enters the small intestine from two sources the diet and bile (Figure 1). Dietary intake of cholesterol is about 300 mg/day (Briefel and Johnson, 2004 Ishinaga et al., 2005 Valsta et al., 2004), whereas the bile contributes 800-1400 mg/day (Duane, 1993 Grundy and Metzger, 1972). The liver not the diet—is therefore the primary source of cholesterol available for absorption, a point that is often underappreciated. Consequently, therapies that block cholesterol absorption are effective at lowering LDL cholesterol mainly because they prevent the reabsorption of endogenous... 

When LDL is abundant in the circulation it provides tissues with an exogenous source of cholesterol. 

Q8 In type 1 diabetes, because of a lack of insulin, a high level of triglyceride is stored in the liver and can subsequently be converted to phospholipids and cholesterol. Hepatocytes synthesize VLDLs, which can be converted to other types of lipoproteins. These lipoproteins are major sources of cholesterol and triglycerides for most other tissues. They leave the liver, enter the blood and can result in rapid development of vascular atherosclerosis. Increased levels of atherogenic oxidized low-density lipoproteins (LDLs) are seen in hyperglycaemic individuals and contribute to macrovascular disease, which is a complication of diabetes mellitus. 

Statins. Statins, such as atorvastatin (Lipotor), simvastatin (Zocor) and lovastatin (Mevacor), are fungal-derived HMG-CoA reductase inhibitors. Treatment results in an increased cellular uptake of LDLs, since the intracellular synthesis of cholesterol is inhibited and cells are therefore dependent on extracellular sources of cholesterol. However, since mevalonate (the product of the HMG-CoA reductase reaction) is also required for the synthesis of other important isoprenoid compounds besides cholesterol, long-term treatments carry some risk of toxicity. 

As cholesterol is used in cell membranes and in the formation of the steroid hormones, and the liver is the most important source of cholesterol synthesis, the liver exports much choiesterol in lipoprotein trams that carry cholesterol (as well as triglycerides) to other areas of the body, where it is used in further syntheses. The liver also exports choiesterol and bile salts into the bile. 

Many investigators identified smoking as a strong risk factor for atherosclerotic renal artery stenosis Hadj-Abdelkader [21] found that 70-80% of patients with this diagnosis were smokers and frequently these stenoses are bilateral [22] and frequently the source of cholesterol microembolism [23]. 

D.A. Freeman and M. Ascoli, Studies on the source of cholesterol used for steroid biosynthesis in cultured Leydig tumor cells, J. Biol. Chem., 1982, 257, 14231-14238. 

As IDL loses apo E and is converted to LDL with apo B-IOO as its sole apoprotein, the residence of LDL in plasma increases from several hours to 2.5 days. This long-lived, cholesterol-rich LDL serves as a source of cholesterol for most tissues of the body although most cells can synthesize cholesterol under normal conditions, most endogenous production occurs in the liver and intestine, from which it is distributed to peripheral tissues by LDL. This arrangement provides an efficient balance between endogenous production and dietary intake of cholesterol. 

The catalyst for this reaction is the enzyme cholesterol esterase (EC 3.1.1.13). Bovine pancreas acetone powder (Sigma Chemical Company), a crude extract from pancreas. Is an inexpensive source of cholesterol esterase activity. This extract contains -15 units of cholesterol esterase activity/gram unit = pmol of ester... 

Carbohydrates are the prime source of glucose manufacture in the body. They are also the only macronutrient we can live better without and the prime source of cholesterol and adipose tissue synthesis. 

Studies of cells in culture have provided considerable information about the control of this pathway [97]. In early studies, cultured skin fibroblasts were maintained for 24 h in a medium containing lipoprotein-deficient serum. These cells showed increased binding of LDL to cell surface receptors and increased HMG-CoA reductase activity. When LDL were added to the medium, binding, uptake, and degradation of the LDL followed. LDL CE were hydrolyzed, and decreased levels of both HMG-CoA reductase and the apo B/E receptor were seen. Furthermore, increased formation of cholesteryl oleate could be demonstrated. In subsequent studies, modified LDL with a net positive charge were used. These cationized LDL were internalized by a mechanism that did not depend on the apo B/E receptor, and that led to a substantial increase in cell cholesterol [103]. Under these conditions there was again increased synthesis of cholesteryl oleate. These findings support two principal conclusions (1) plasma lipoprotein CE is an important source of cholesterol for fibroblasts and similar cells and (2) the formation of intracellular... 

One source of cholesterol for humans is meat. Vegetarians eliminate this cholesterol contribution. Yet vegetarians can still develop atherosclerosis. How can this be ... 

Reconstituted spherical HDL can be made by co-sonication of selected HDL components (e.g., apo Al, PC, CE) or by extensively reacting discoidal reconstituted HDL with LCAT in the presence of an exogenous source of cholesterol. The products are spheroidal and, like the discoidal precursor particles, contain two, three, or four apo Al molecules per particle, PC, cholesterol, and a CE core. The diameters of the particles range from 80 to 120 A. Although not well studied, the conformation of apo Al appears distinct from that in the discoidal particles and is variable depending on the particle diameter (A. Jonas, 1990 M.G. Sorci-Thomas, 2002). 

Several sources of cellular cholesterol contribute to RCT. Part of the process of RCT reflects peripheral (extra-hepatic) cholesterol synthesis. Despite the down-regulation of cholesterol synthesis mediated by the LDL receptor via the delivery of LDL, a considerable amount of sterol is made in peripheral tissues. The importance of this source of cholesterol to homeostasis may be as great as that of dietary cholesterol in many individuals. After hydrolysis of LDL-CE by cellular cholesterol esterases, this cholesterol is made available for recycling to the cell surface and can be recovered there by apo A1 for incorporation into HDLs. Cholesterol is also available from VLDLs, LDLs, and chylomicrons directly internalized by peripheral cells. Cholesterol from HDLs bypasses the lysosomal pathway and becomes part of recycling endosomes that return to the cell surface. Some of the cholesterol recovered on HDLs originates from blood cells. Finally, some cholesterol is transferred directly to other lipoproteins from chylomicrons, VLDLs, and LDLs, without entering the cell. 

The overall benefits from, and consequences of, this LDL receptor-mediated regulatory system are the coordinated utilization of intracellular and extracellular sources of cholesterol at the systemic level. Mammalian cells are able to subsist in the absence of lipoproteins because they can synthesize cholesterol from acetyl-CoA. When LDL is available, however, most cells primarily import LDL cholesterol and keep their own synthetic activity suppressed. Thus, a constant level of cholesterol is maintained within the cell while the external supply in the form of lipoproteins can undergo large fluctuation. 

The primary source of cholesterol is the liver. After cholesterol is produced, the liver packages cholesterol molecules with proteins in units known as lipoproteins, which are then distributed throughout the body by way of the bloodstream. Some cholesterol is deposited in cells, where it is used as the raw material in the synthesis of a number of biologically essential compounds, such as vitamin D3, steroids (such as estrogen and testosterone), and the bile acids, used by the body to digest foods. Excess cholesterol not needed by cells remains in the bloodstream until it is returned to the liver. 

Enjoy your eggs. This nearly perfect food once had a bad rap as a dangerous source of cholesterol, but nutritionists now understand that eggs are actually good for your heart and circulation, especially if you get them from farm-raised free-range chickens, and even more so if you eat eggs from flax-fed chickens, which inserts some brain-healthy Omega-3 into your diet. 

Morton, G.M. et al. (1995). Intakes and major dietary sources of cholesterol and phytosterols in the British diet, J. Human Nutr. Dietet., 8, 429. 

List the sources of cholesterol and outline the mechanisms of regulation of cholesterol biosynthesis. 

The main source of cholesterol for cells outside the liver and intestine is from circulating LDL. Cholesterol released during the degradation of LDL suppresses the formation of new LDL receptors, thereby decreasing the uptake of exogenous cholesterol by the cell. 

EXAMPLE 12.16 What are the main dietary sources of cholesterol ... 

Brain is the richest source of cholesterol in the body aceounting approximately 23% of total body cholesterol. Most brain cholesterol is present in myelin, neural... 

Another, similar, vesicle is the low-density hpoprotein (LDL), which is a major carrier of cholesterol. Cancer cells avidly absorb LDL as a source of cholesterol for their rapidly dividing cells. The LDL can be isolated and their cholesterol core replaced by hydrophobic carboranes. In vitro studies of hamster V-79 cancer cells have shown that such boronated LDLs resulted in intercellular concentrations of 240 (tg B/cell, which is about lOx the amount needed for effective BNCT. The use of drug laden vesicles, such as liposomes or LDLs, also take advantage of a general phenomenon of the enhanced permeability and retention (EPR) effect. ... 

Cholesterol synthesis inhibition leads to cell proUferation inhibition provided the cell has no alternative source of cholesterol, which is easily achieved in vitro by incubating the cells in the absence of Upoprotein in the medium (Vitols et al. 1994). In LDL-receptor deficient cells, the effect of cholesterol synthesis inhibition on cell growth is not prevented by adding LDL to the medium, illustrating the role of LDL receptor in the provision of cholesterol for cell proUferation (Cuthbert et al. 1986, MartInez-Botas etal. 1999). Lovastatin blocked HL-60 cell proUferation (MartInez-... 

Low in cholesterol, low cholesterol, contains a small amount of cholesterol, low source of cholesterol, ot little cholesterol ... 

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