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Since cholesterol is essential for the whole animal world, it is primarily synthesized from simple substances in the body. However, the high level of circulation in the blood, depending on how it is transported in lipoproteins, were significantly associated with progression of atherosclerosis. For a man of about 68 kilograms (150 pounds), a typical synthesis of cholesterol the body makes about 1 gram (1000 mg) per day, and the total content of the body is about 35 г. typical daily dietary intake more in the United States and companies with similar dietary power is 200-300 mg. Tel compensate cholesterol, reducing the amount synthesized.
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Recycled cholesterol. He stands in the liver with bile in the gastrointestinal tract. Usually about 50% of the allocated cholesterol absorbed by the small intestine back into the bloodstream. Tract absorption of very selective cholesterol, excreting plant stanols and sterols (which contribute to the progression of atherosclerosis more than cholesterol), back into the lumen of the intestine for elimination.
[edit] Functions

Cholesterol is necessary for the establishment and maintenance of membranes, regulates membrane fluidity in the range of physiological temperatures. Hydroxyl groups on cholesterol interacts with the polar head groups of membrane phospholipids and sphingolipids, and bulky steroid and the hydrocarbon chain embedded in the membrane, along with the nonpolar chain fatty acids from other lipids. In this structural role of cholesterol reduces the permeability of plasma protons (positive hydrogen ions) and sodium ions. [5]

The cell membrane, cholesterol is also functioning in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of caveolae invaginate and clathrin-coated pits, including the fossa-dependent and clathrin-dependent endocytosis. Role of cholesterol in endocytosis can be studied using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol also been implicated in the processes of intracellular signal aid in the formation of lipid rafts in the plasma membrane. In many neurons, myelin sheath, rich in cholesterol, since it derives from the compacted layer of Schwann cell membrane, provides insulation for more efficient conduction of impulses. [6]

Inside the cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted into bile, which is then stored in the gall bladder. Bile contains bile acid salt, which dissolves the fat in the gastrointestinal tract and aid in the intestinal absorption of fat molecules, as well as fat-soluble vitamins, vitamin A, vitamin D, vitamin E and vitamin C. Cholesterol is an important precursor molecule of the synthesis of vitamin D and steroid hormones, including corticosteroids, cancer of cortisol and aldosterone, as well as the sex hormones progesterone, estrogen and testosterone, as well as their derivatives.

Some studies suggest that cholesterol may act as an antioxidant [7].
[edit] Dietary sources

Animal fats are complex mixtures of triglycerides, with a smaller number of phospholipids and cholesterol. As a result, all products containing animal fat contain cholesterol, in varying degrees. [8] The main sources of dietary cholesterol include cheese, egg yolk, beef, pork, poultry and shrimp. [9] Human breast milk also contains significant amounts of cholesterol. [10] Cholesterol is not present in plant sources of food, if it was added during the preparation of food. [9] However, plant products, such as flax seeds and peanuts contain cholesterol-like compounds called phytosterols, which have offered to help lower serum cholesterol. [11]

Total consumption of fats, especially saturated fats and trans fats [12], plays an important role in blood cholesterol than the intake of cholesterol itself. Saturated fat is present in its dairy products, animal fats, oils and several types of chocolate. Trans fats are usually obtained by partial hydrogenation of unsaturated fats, and, unlike other types of fats, are not found in significant quantities in nature. Research supports the recommendation to minimize or eliminate trans fats from the diet because of their adverse health effects. [13] Trans-fats are most often found in margarine and hydrogenated vegetable fats, and consequently, many fast foods, snacks, and fried or baked goods.

Changes in diet, along with other lifestyle changes can help reduce cholesterol in the blood. Avoid animal products can reduce cholesterol in the body is not by reducing dietary cholesterol alone, but mainly through the reduction of saturated fat. Those wishing to reduce their cholesterol by making changes in diet should be designed to consume less than 7% of daily calories from saturated fat and less than 200 mg of cholesterol per day. [14]

Agree that changes in diet (for certainty, reduce consumption of fats and cholesterol) can reduce blood cholesterol levels and thereby reduce the likelihood of development, in particular, coronary heart disease (CHD) has been questioned. An alternative view is that any reduction of dietary cholesterol opposition from bodies such as the liver, which will increase or decrease the production of cholesterol in order to keep the level of cholesterol in the blood continuously. [15]
[edit] Synthesis

Approximately 20-25% of the total daily production of cholesterol occurs in the liver and other objects of high-level synthesis include the intestines, adrenal glands and genital organs. Synthesis in the body begins with one molecule of acetyl-CoA and one molecule of atsetoatsetil-CoA, which are dehydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is reduced to mevalonate enzyme HMG-CoA reductase. This step is an irreversible step in the synthesis of cholesterol and is the site of action for statins (HMG-CoA reductase).

Mevalonate then converted a 3-isopentenyl pyrophosphate in the three reactions that require ATP. This molecule is decarboxylated to isopentenyl pyrophosphate, which is one of the key metabolites for various biological reactions. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate and then condenses in the form of action of squalene squalene synthase endoplasmic reticulum. Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is then converted to cholesterol. [16]

Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine in 1964 for discoveries concerning the mechanism and regulation of cholesterol and fatty acids.
[edit] Regulation of cholesterol synthesis

The biosynthesis of cholesterol is directly regulated by the level of cholesterol present, although homeostatic mechanisms involved in only partially understood. Higher dietary intake leads to an overall reduction in local production, while the lower dietary intake has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum protein in SREBP (sterol regulatory element-binding protein 1 and 2). [17] In the presence of cholesterol, SREBP is connected with two other proteins: SCAP (SREBP-cleavage-activating protein) and Insig1. When cholesterol levels fall, slim-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the Golgi apparatus, where SREBP is split by S1P and S2P (site-1 and -2 proteases), two enzymes that are activated by SCAP, when cholesterol levels are low. Cleaved SREBP then migrates to the nucleus and acts as a transcription factor to bind to the SRE (sterol regulatory element), which stimulates the transcription of many genes. Among these LDL receptors and HMG-CoA reductase. The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to increased production of endogenous cholesterol. [18] Much of this signaling pathway was explained Dr. Michael Brown and Dr. Goldstein in 1970. In 1985 they received the Nobel Prize in Physiology or Medicine for their work. Their subsequent work shows how the path SREBP regulates the expression of many genes that control the formation and lipid metabolism and distribution of fuel the body.

Synthesis of cholesterol may be turned off when cholesterol levels are high as well. HMG-CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and the membrane domain. Membrane function domain sense signals for its degradation. Increasing the concentration of cholesterol (and other sterols) cause changes in the oligomerization of this state, which makes it more receptive to the destruction of the proteosome. This enzyme activity can also be reduced by phosphorylation of AMP-activated protein kinase. Since this kinase is activated by AMP, which is obtained by the hydrolysis of ATP, it follows that cholesterol synthesis stops when low levels of ATP [19].
[edit] The plasma transport and regulation of absorption
See also: blood lipids

Cholesterol is poorly soluble in water, it can dissolve and travel in water-based blood in extremely small concentrations. Since cholesterol is insoluble in blood, it is transported in the circulatory system within lipoproteins, complex spherical particles that consist of external amphiphilic proteins and lipids facing the outer surface of the water-soluble and fat-soluble inner-facing surfaces; triglycerides and cholesterol esters are carried out within the country. Phospholipids and cholesterol, being amphipathic, carried on the surface of the monolayer particles lipoproteins.

In addition to providing a means for transporting soluble cholesterol, lipoproteins is a cell-targeting signals that direct lipids they carry certain tissues. For this reason, there are several types of lipoproteins within the blood is called, in order of increasing density, chylomicrons, very-low-density lipoprotein (VLDL), the average density lipoprotein (IDL), low-density lipoprotein (LDL) and high density lipoprotein (HDL). More cholesterol and less protein, lipoprotein, it is less dense. Cholesterol in all the various lipoproteins are identical, although some of the cholesterol is carried as "free" Alcohol and some carried as fatty acyl esters are called esters of cholesterol. Nevertheless, the various lipoproteins contain apolipoproteins, which serve as ligands for specific receptors on cell membranes. Thus, the particle density lipoprotein molecular addresses, definition of the beginning and ends of cholesterol transport.

Chylomicrons, the least dense type of cholesterol transport molecules, contain apolipoprotein B-48, apolipoprotein C and apolipoprotein E in their shells. Chylomicrons carriers that carry fats from the intestine into the muscles and other tissues that need fatty acids for energy production or fat. Cholesterol, which is not used muscles remain in a more cholesterol-rich remnants of Metabolism, which will be taken from the blood into the liver.

VLDL molecules produced in the liver and excessive triacylglycerol and cholesterol, which is not required in the liver to synthesize bile acids. These molecules contain apolipoprotein B100 and apolipoprotein E in their shell. During transport in the blood, blood vessels break down and absorb more triacylglycerol leave IDL molecules that contain an even higher percentage of cholesterol in the blood. IDL molecules have two possible outcomes: Half of them were examined in the liver for the metabolism of other biomolecules, and the other half continue to lose triglycerides in the blood until they form of LDL molecules that have the highest percentage of cholesterol in them.

LDL molecules, therefore, are the main carriers of cholesterol in the blood, and each of them contains about 1500 molecules of cholesterol ester. Shell LDL molecule contains only one molecule of apolipoprotein B100, which is recognized by LDL receptors in peripheral tissues. After mandatory apolipoprotein B100, many of LDL receptors are localized in clathrin-coated pits. Both LDL and its receptor endocytosis in the form of internalized vesicles within the cell. Vesicle then fuses with lysosomes, which is called the lysosomal enzyme acid lipase, which hydrolyzes esters of cholesterol. Now in the cell, cholesterol can be used for membrane biosynthesis or esters and stored inside the cell, so as to not interfere with the cell membranes.

The synthesis of LDL receptors is regulated by SREBP, the same regulatory protein, which was used to control cholesterol synthesis anew in accordance with the presence of cholesterol in the cell. When a cell has abundant cholesterol, LDL receptor synthesis is blocked, to a new level of cholesterol in the form of LDL molecules can not be accepted. On the contrary, more LDL receptors are made when the cell is deficient in cholesterol. When deregulated the system, many molecules of LDL appear in the blood without the receptors on peripheral tissues. These molecules are oxidized LDL and taken up by macrophages, which become engorged and the cells form foam. These cells often become trapped in the walls of blood vessels and contribute to artherosclerotic formation of plaque. These plaques are a major cause of heart attacks, strokes and other serious health problems, leading to the association of so-called low-density lipoprotein (actually lipoproteins) with a "bad" cholesterol [19].

In addition, particles of HDL, is believed to transport cholesterol back to liver for excretion or other tissues that use cholesterol for the synthesis of hormones in a process known as reverse cholesterol transport (RCT) [20]. Presence of large numbers of large HDL particles correlates with better health. [21] In contrast, having a small number of large HDL particles independently associated with atheromatous disease progression in the arteries.