Cholesterol in cell

The polyene macrolide filipin was isolated in 1955 from the cell culture filtrates of Sterptomyces filipinensis, and was later shown to be a mixture of four components [36]. Although too toxic for therapeutic use, the filipin complex has found widespread use as a histochemical stain for cholesterol and has even been used to quantitate cholesterol in cell membranes [37]. The flat structure of filipin III, the major component of the filipin complex, was assigned from a series of degradation studies [38]. Rychnovsky completed the structure determination by elucidating the relative and absolute stereochemistry [39]. The total synthesis plan for filipin III relied heavily on the cyanohydrin acetonide methodology discussed above. 

Eukaryotes (single cell) Plant-like Fungal-like Animal-like Cholesterol in cell s membrane compartments, nucleus, filaments, Ca2+ signals Photosynthetic, sedentary Dependent on plants, sedentary Dependent on digestion, mobile Use of Cu, Zn... 

One role of high density lipoprotein (HDL) is to collect unesterified cholesterol from cells, including endothelial cells of the artery walls, and return it to the liver where it can not only inhibit cholesterol synthesis but also provide the precursor for bile acid formation. The process is known as reverse cholesterol transfer and its overall effect is to lower the amount of cholesterol in cells and in the blood. Even an excessive intracellular level of cholesterol can be lowered by this reverse transfer process (Figure 22.10). Unfortunately, the level of HDL in the subendothelial space of the arteries is very low, so that this safety valve is not available and all the cholesterol in this space is taken up by the macrophage to form cholesteryl ester. This is then locked within the macrophage (i.e. not available to HDL) and causes damage and then death of the cells, as described above. 

Of the various lipid components of the lipoproteins, only the biosynthesis of cholesteryl esters has not yet been mentioned. Cholesteryl ester is the storage form of cholesterol in cells. It is synthesized from cholesterol and acyl-CoA by acyl-CoA cholesterol acyltransferase (ACAT) (fig. 20.13), which is located on the cytosolic surface of hepatic endoplasmic reticulum. Acylation of the 3 hydroxyl group of cholesterol eliminates the polarity of cholesterol and facilitates the packing of cholesterol as its ester in the core of the lipoprotein or for storage in lipid droplets within cells. 

Carr AC, van den Berg JJM, Winterboum CC (1996) Chlorination of Cholesterol in Cell Membranes by Hypochlorous Acid. Arch Biochem Biophys 332 63... 

ABCA1 mediates the first step in the energy-dependent efflux of cholesterol from the cell to form HDL for reverse cholesterol transport (Fig. 15-2). While all tissues in the body can synthesize cholesterol, only the liver and steroidogenic tissues can metabolize it. Surplus cholesterol in cells of the peripheral tissues is transported to the liver for either redistribution to other cells or for excretion either as free cholesterol or as a bile salt after conversion in the liver. Therefore, this reverse cholesterol transport system plays a pivotal role in cholesterol homeostasis with HDL as one of the key players. 

Cholesterol is a basic constituent of cell membranes and is known to affect their properties [10]. Thus experiments with liposomes incorporating varying amounts of cholesterol may simulate the function of cholesterol in cell mem-... 

The cholesterol in cell membranes occurs as free cholesterol, rather than as choJesteryl esters. As illustrated in Figure 6.21, this cholesterol can be removed and transfern to circulating HDLs in a reaction catalyzed by lecithin choLesterol acy(transferase (LCAT). Continued insertion of cholestery l esters into an HDL changes its initial disk shape to a sphere shape. The lipid-poor HDLs (diskshaped HDl. ) account for only a few percent of the HDLs in the bloodstream. 

MVA is now known to be metabolized by routes other than those which give rise to terpenoids and steroids. The breakdown occurs predominantly in the kidneys to give C2 units that can be utilized in fatty-acid synthesis. The sterol and the shunt pathways have been evaluated in nine different tissues of rat previous conclusions that the kidneys are the predominant site of both types of metabolism have been confirmed. MVA is known to accumulate, at a low level, in the blood, and these results suggest that impairment of renal clearance of serum MVA by either route may account for the hypercholesterolaemia associated with some kidney disorders. A study of the effects of possible antimetabolites of MVA (for example the 2,3-anhydro-compound) on the formation of cholesterol in cell-free systems from liver has been reported. ... 

HMG-CoA reductase is the major regulatory enzyme in cholesterol biosynthesis. HMG-CoA reductase is controlled hormonally by insulin and glucagon and transcription and translation of the enzyme can be suppressed by the presence of cholesterol in cells. 

HMG-CoA reductase is the major regulatory enzyme in cholesterol biosynthesis. HMG-CoA reductase is controlled hormonally by insulin and glucagon and transcription and translation of the enzyme can be suppressed by the presence of cholesterol in cells. Mevalonate is converted in the cytosol to the five carbon building blocks of isoprene synthesis-isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DPP)-in the reactions shown in Figure 19.19. Subsequently, IPP and DPP form famesyl pyrophosphate in the cytosol (Figure 19.20)... 

In addition to dietary therapy, aimed at reducing her blood cholesterol levels, Ann Jeina was treated with pravastatin, an HMG-CoA reductase inhibitor. The HMG-CoA reductase inhibitors decrease the rate of synthesis of cholesterol in cells. As cellular cholesterol levels decrease, the synthesis of LDL receptors increases. As the number of receptors rises on the cell surface, the uptake of LDL is increased. Consequently, the blood level of LDL cholesterol decreases. 

Problem 19.36. What is the function of cholesterol in cell membranes ... 

Excess accumulation of free cholesterol in cells stimulates the rate of cholesterol ester formation and induces deposition of cholestryl ester inclusions in the cytoplasm similar to the situation in the foam cells of atherosclerotic plaque. 

High blood cholesterol and lipoproteins—Total blood cholesterol is an indicator of a heart attack. Even better indicators are the level of the lipoproteins which carry cholesterol in the blood specifically, high-density lipoproteins (HDL) and low-density lipoproteins (LDL). HDL has a protective role since it transports cholesterol back to the liver, while LDL seems to deposit cholesterol in cells, including blood vessels. Also, evidence indicates that high HDL decreases the risk of heart attack while high LDL increases the risk. 

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