17:18
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Cholesterol is a waxy fat steroids in the liver or intestine, produced for the synthesis of hormones and cell membranes are used and transported in the blood plasma of all mammals. Cholesterol is an important structural component of the plasma membrane of mammals for maintaining proper membrane permeability and fluid requirements. It is also an important tool for the production of bile acids, steroid hormones and vitamin D. He is the main steroid are animals, but also produces small quantities in plants and fungi to synthesize necessary. Cholesterol is totally absent from prokaryotes. When their concentration in the blood increases the risk of heart disease by increasing the level should be controlled. The word cholesterol from the Greek word origins and was discovered by François de La Salle Poulletier solid form in gallstones in 1769, but the chemical was identified by Eugène Chevreul in 1815, the concept of cholesterol had been done.
Physiology
Cholesterol is involved in the synthesis of male and female steroid hormones, particularly testosterone and estrogen. Approximately 80% of the body cholesterol is synthesized in the liver, while the rest comes from our diet. The main sources of cholesterol in the diet are meat, fish, poultry and dairy products. Among the meat, liver, high cholesterol, cholesterol while foods of plant origin. After a meal, cholesterol is absorbed from the intestine and wrapped in a protein coat. This cover-protein complexes cholesterol as chylomicrons, which are then stored in the liver known. The liver has the ability to regulate cholesterol in the blood. Cholesterol synthesis is based on simple elements in the body. In the blood is transported in lipoproteins, and if the level rises and increases the risk of atherosclerosis. Typically for a person weighing 68 kg for the synthesis of cholesterol, 1 g per day. The extra day of cholesterol in the United States 200-300 mg. The body maintains a balance by the minimization of the total amount synthesized in the body, when the supply of cholesterol.
Cholesterol is also recycled, is eliminated by the liver via the bile into the digestive tract. Approximately 50% of the excreted cholesterol absorbed by the small intestine and reaches the bloodstream. Phytosterols compete with cholesterol absorption in the intestine and thus cholesterol. Cholesterol is a fat in the body in small quantities are needed. High levels of cholesterol in the blood can lead to conditions of coronary artery disease and angina pectoris. Nitrates are found to relieve angina. Most people have regular tests to draw blood cholesterol, triglycerides, which consist of the study, high-density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol.
Methods for increasing good cholesterol and lowering cholesterol in the blood cholesterol, including statins, fibrates, niacin and bile acid sequestrants. These drugs are not able to reverse the calcification of the coronary arteries are blocked when a heart attack. The two main types of cholesterol are high-density lipoprotein (HDL) and low density lipoprotein (LDL). For simplicity, the LDL cholesterol HDL the good cholesterol is known as long as the bad cholesterol. We can see that the bad cholesterol that is responsible for the formation of plaque in arteries and therefore the risk of heart attack increases. Transport of cholesterol good cholesterol in the other plate by hand and returned to the bloodstream for excretion by the liver.
Type
There are three main types of lipoproteins in fasting serum lipoproteins informed, low density (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL) found.
The first low-density lipoprotein (LDL) or bad cholesterol, and management
LDL or bad cholesterol comprises 60-70% of total serum cholesterol. It is important atherogenic lipoprotein-lowering therapy in high cholesterol are dangerous. Cholesterol deposits in artery walls, which calls for the formation of a hard substance, such as cholesterol plaque. This board is responsible for the hardening of the arteries, making them narrow and the process is called atherosclerosis. The liver not only produces and secretes LDL cholesterol into the blood, but also removes the blood. A large number of active receivers on the surface of the liver, which actively bind to molecules of LDL cholesterol and remove the blood. LDL receptor deficiency is associated with high levels of molecules in the blood.
Some benefits are known as reducing levels of bad cholesterol, for example, decay reduced the formation of new plaques in artery walls, removing existing plaques in the arteries, the veins are normal shape, preventing plaque rupture, formation of blood clots and possibly the risk of heart attack is easier. Several studies have shown that reducing the risk of heart attack by 25% for every 10% reduction in LDL cholesterol and is the decisive factor in the total cholesterol in the blood reached a safe area. A study of 4,000 people confirmed that the bad cholesterol and the risk of heart attack by 25% and 42% reduction in the statin. Is it viable is that the daily consumption of calories from fat to 30% and reduced the consumption of different types of food should be rich in carbohydrates, proteins, because the body that increases triglycerides, which are then stored as fat.
Foods high in saturated fat increases LDL-cholesterol in the blood. Fats can be classified as saturated and unsaturated. Saturated fats are readily available in meat, dairy products and certain vegetable oils, especially coconut oil, palm oil and cocoa available. Therapeutic lifestyle changes to reduce levels of bad cholesterol, regular exercise taken, losing weight and a diet low in saturated fat and cholesterol. When lifestyle changes, the desired results are not considered drugs. Statins are the drugs most effective in giving the best results at the level of bad cholesterol and reduces the risk of heart disease. Other drugs that can be used are gemfibrozin fibrates, such as cholestyramine, and ezetimibe Zetia. National Institutes of Health, the American Heart Association and the American College of Cardiology some guidelines to help medical experts for dealing with high cholesterol free.
Two high-density lipoprotein (LDL) or good cholesterol and its benefits
HDL or good cholesterol, prevent atherosclerosis by removing cholesterol from artery walls and their elimination by the liver. High levels of LDL cholesterol and HDL cholesterol are at lower risk of heart disease. Therefore, the levels maintained a healthy and happy and enjoy life. HDL cholesterol is 20-30% of total serum cholesterol. Because it reduces the risk of atherosclerosis reduces the amount should be checked occasionally. Heredity and diet have a major impact on the individual HDL, LDL and total cholesterol. Families with low levels of HDL have an increased risk of heart attack and vice versa. Lifestyle and other factors affecting HDL levels. HDL are low in people who smoke, obesity, physical inactivity and diabetes mellitus type II. HDL levels are higher in people who are thin, regular exercise and not smoking. Estrogens also increase HDL levels that women higher levels of HDL cholesterol than men.
LDL cholesterol is easier to raise HDL cholesterol. The reduction of LDL and HDL increases have a positive effect on the health of the individual. Previous researchers have a lot more about how the level of bad cholesterol, but with the progress of the investigation, it became clear that it is better to increase the levels of good cholesterol lowers bad cholesterol because it automatically is concentrated. Levels can be affected by weight reduction, regular exercise and increased consumption of niacin. Some studies suggest that statins and niacin, in combination with better results and women with high HDL lower risk of heart attack. The mean HDL levels in women must be between 50 to 55 mg dl / dl in men and mg / 40-50. Total cholesterol and HDL cholesterol may be useful to estimate the risk of atherosclerosis. An average ratio should be between 4-5.
Studies have shown that even a small increase in HDL cholesterol may reduce the risk of a heart attack. For each 1 mg / dl increase in HDL-cholesterol, reduces the risk of heart disease in 4.2%. However, the therapeutic lifestyle changes to help raise HDL levels. If these changes do not yield positive results after taking drugs. Regular aerobic exercise, losing weight and quitting smoking are useful for increasing HDL levels. Regular consumption of alcohol can help, such as one drink per day in this area, but many side effects alcohol consumption is related to the health of this criterion has been ignored. Effective drugs are gemfibrozil, estrogen and lower doses of statins. A new drug is the most successful and fenofibrate in reducing serum triglycerides.
Third triglycerides or lipoprotein of very low density lipoproteins (VLDL) and their effects or ugly
Lipoprotein cholesterol, triglycerides are ugly, that 10-15% of total serum cholesterol accounts. Cholesterol is produced by the liver and some VLDL remnants seem to promote atherosclerosis similar to LDL. Triglycerides are a type of fat transported to the tissues by blood. Most body fat consists of triglycerides. Serum triglycerides can be drawn from two sources. The first source is the food we eat, for example, when we eat a diet rich in fats in the intestine and enter some of them during the rest transported to the liver. The second source is the liver itself. When fats are absorbed in the liver, the fatty acids needed by fat cells and converts them into packets of triglycerides, which was later published as a fuel. There is some controversy about the fact that high levels of triglycerides are responsible for the disease or not.
Other clinical outcomes often with a high level of triglycerides in the blood pressure, obesity, diabetes, chronic kidney disease, liver and heart disease and hypothyroidism. Hereditary in certain high levels of triglycerides are people, and this condition has been identified as hypertriglyceridemia. The best known examples of hypertriglyceridemia mixed hypertriglyceridemia, familial hypertriglyceridemia and dysbetalipoproteinemia. Hypertriglyceridemia may also occur due to non-genetic factors such as obesity, alcohol abuse, diabetes mellitus, kidney disease and the use of estrogen-containing medications, such as the pill. Levels back to normal, without medication, with the help of a doctor. The first step was to treat hypertriglyceridemia involves the administration of a diet low in fat with reduced consumption of sweets, regular aerobic exercise, losing excess weight, alcohol and reduce snuff. In patients with diabetes mellitus, an effective control of blood glucose in the blood is necessary.
If necessary medications, statins, fibrates and niacin can be used. Fibrates not only reduce triglyceride levels, but also to increased levels of HDL and LDL particle size of molecules. Same task is performed by niacin, but decreases the rate of Lp (a) and cholesterol. Statins, on the other hand, lower triglycerides and LDL, but are not effective in raising HDL levels. A recently published drug fenofibrate has promising results in reducing the levels of triglycerides and LDL cholesterol and raise HDL levels, particularly in individuals with an optimal response, illustrated with fibrates. For some people, a combined dose of fenofibrate with a statin or fibrate necessary for best results.
Function
Cholesterol is needed for the creation and maintenance of membranes and modulates membrane fluidity over a wide range of physiological temperatures. The hydroxyl group on cholesterol molecule reacts with the polar headgroups of membrane phospholipids and sphingolipids, causing the membrane permeability for protons. Within the cell membrane, which also works in the performance of the cell transport, signaling and intracellular nerve. Cholesterol is also very important for the structure and function of invaginated caveolae and coated pit endocytosis. Recently it was suggested that cholesterol also plays a role in cell signaling processes, helping in the formation of lipid rafts in the plasma membrane. In many neurons, a myelin sheath rich in cholesterol is present, from compressed layers of the membrane-derived Schwann cells to aid in efficient nerve conduction. This layer also provides insulation. In cells, cholesterol serves as a precursor to a number of biochemical processes. In the liver, cholesterol in the bile, which is then stored in the gallbladder. The bile is rich in bile salts dissolve the active molecules of fat in the digestive tract and in the intestinal absorption of fat molecules and fat-soluble vitamins A, D, E and K. help is also an important precursor for the synthesis of vitamin D and steroid hormones.
Biosynthesis and regulation
All animal cells produce cholesterol, but production varies with the type of cells and organs. 20-25% of the daily production of cholesterol in the liver and the rest of the colon, adrenal glands and reproductive organs. The synthesis of cholesterol in the body starts with a molecule of acetyl-CoA and acetoacetyl-CoA from one molecule, which is hydrated to form the 3-hydroxy-3-methyl-CoA (HMG-CoA). HMG-CoA to mevalonate is formed is reduced by the enzyme HMG-CoA reductase to form. This step is irreversible and rate-limiting step in cholesterol synthesis. Mevalonate is formed, it is necessary to have a 3-isopentenyl pyrophosphate in three reactions are ATP. Mevalonate isopentenyl pyrophosphate is then decarboxylated form. Isopentenyl pyrophosphate and three molecules together to form farnesyl pyrophosphate in the presence of geranyl transferase. Two molecules of farnesyl pyrophosphate, squalene is in the endoplasmic reticulum to form and to the reaction catalyzed by squalene synthetase. Lanosterol cyclase Oxidosqualene converts squalene, ultimately leading to cholesterol. The regulatory mechanism of cholesterol and is used by Bloch and Feodor Lynen Konard, the Nobel Prize in Physiology or Medicine was awarded in 1964.
Cholesterol under the strict control of blood cholesterol, but the mechanisms involved in their homeostatic regulation partially understood. A higher intake of cholesterol results in a marked decrease in endogenous production, and vice versa. The main mechanism involved includes the detection of intracellular cholesterol to the protein (the protein binding of sterol regulatory element 1 and 2) SREBP from the endoplasmic reticulum. It binds cholesterol in the presence of this protein with two other proteins, ie, the SCAP (SREBP activation protein-splitting) and INSIG first or cholesterol decreases SREBP complex dissociates to INSIG-an PAP, so this complex at the entrance to the Golgi where SREBP is cleaved by proteases S1 and S2. These proteases are activated by SCAP when cholesterol levels fall. The cleaved SREBP migrates over to the nucleus as a transcription factor, and is then connected to the sterol regulatory element (SRE), the transcription of many genes promoting, for example, the interception of circulating blood volume LDL low-density lipoprotein (LDL) and increase of the body's production of cholesterol in the HMG-CoA reductase. Much of this route was developed by Dr. Michael S. Brown and Joseph L. Goldstein, Ph.D., in the year 1970, received the Nobel Prize for his work in 1985.
Cholesterol synthesis may be terminated if cholesterol is high. HMG-CoA reductase, contributes to both the cytosolic and membrane domains. The surface of the membrane is sensitive to signals that are required for removal. High levels of cholesterol results in a change in the state of oligomerization domain, making them more susceptible to destruction by the proteasome. The activity of this enzyme is also the phosphorylation of protein kinase activated by AMP are reduced. Cholesterol is only slightly soluble in water and can be dissolved in the aqueous blood, but moves at very low concentrations. Because cholesterol is not soluble in the blood, is transported to the movement in the lipoprotein complex, the exterior is composed of protein and lipid amphiphiles. Triglycerides and cholesterol esters are carried internally. Lipoprotein cholesterol is soluble in the blood and therefore lipoproteins are transported in different forms in chylomicrons say blood, very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) lipoprotein density lipoprotein (LDL) and high density lipoprotein performed (HDL).
The chylomicrons are transported to the less dense type of cholesterol molecules, whose shells are rich in apolipoprotein B-48, C and apolipoprotein E. They are fat, needed in the intestines, muscles and other tissues, fatty acids into energy. Cholesterol, not the muscles remain in the form of chylomicron remnants, which are then eliminated by the liver via the blood. Molecules are produced by VLDL triglyceride and cholesterol in the liver, not liver to produce bile acids necessary costs. These molecules contain apolipoprotein B100 and apolipoprotein E in the shell. While the distribution of the transport of blood vessels and take the IDL triglyceride molecules that have a high concentration of cholesterol. LDL molecules are the main carrier of cholesterol in the blood and each molecule contains about 1500 cholesterol esters. The shell of the LDL molecule contains a single molecule of apolipoprotein B100, which is recognized by LDL receptors in peripheral tissues. While the binding of apolipoprotein B100 and LDL receptors are located in many coated pits. LDL and its receptors are made by endocytosis, vesicles in the cell that fuses with lysosomes to lysosomal acid lipase, which hydrolyzes cholesterol esters to form. At this stage can be used for the cholesterol biosynthesis of the membrane and can be stored in the cell.
Protein synthesis of the LDL receptor is regulated by SREBP. If the cell has enough cholesterol, LDL receptor synthesis is blocked and no more cholesterol molecules in the cell. If the cell is the lack of LDL cholesterol receptors are formed. If this system is more LDL LDL receptor molecules was liberalized in the bloodstream, especially in the vicinity of the peripheral tissues. These molecules are oxidized and forms of macrophage foam cells contributes to the formation of atherosclerotic plaques on the walls of arteries causing a heart attack more. HDL molecules to participate in reverse cholesterol transport, as he returned to the liver for excretion. Cholesterol is susceptible to oxidation and can easily form oxysterol, such as derivatives of oxygen. Oxysterol can be generated by three main mechanisms of auto-oxidation, oxidation secondary to lipid peroxidation and the enzymatic oxidation of cholesterol metabolism. Oxysterol in the biosynthesis of bile acids, cholesterol and transport of various forms of regulation of transcription of the genes involved.
Cholesterol is oxidized by the liver into a variety of bile acids, which in turn, conjugated with glycine, taurine, glucuronic acid. A mixture of conjugated bile acids conjugated with two cholesterol from the liver is excreted in the bile. Approximately 95% of bile acids absorbed by the intestine, while the rest is lost in the stool. Excretion and reabsorption of bile acids are the basis of the enterohepatic circulation is essential for digestion and absorption of fats in the diet. In certain circumstances, cholesterol crystallizes, forming gallstones, especially in the gallbladder. Lecithin and bilirubin gallstones also occur are known, but their share is low. Every day, approximately 1 g of cholesterol is known as the colon, go into the food, the bile is the elimination of intestinal cells and can be metabolized by intestinal bacteria. Cholesterol is excreted primarily in a non-absorbable sterols coprostanol in stool. Cholesterol-lowering bacterium was isolated from human feces. Some derivatives of cholesterol known cholesteric liquid crystalline phase to produce. Cholesterol
Physiology
Cholesterol is involved in the synthesis of male and female steroid hormones, particularly testosterone and estrogen. Approximately 80% of the body cholesterol is synthesized in the liver, while the rest comes from our diet. The main sources of cholesterol in the diet are meat, fish, poultry and dairy products. Among the meat, liver, high cholesterol, cholesterol while foods of plant origin. After a meal, cholesterol is absorbed from the intestine and wrapped in a protein coat. This cover-protein complexes cholesterol as chylomicrons, which are then stored in the liver known. The liver has the ability to regulate cholesterol in the blood. Cholesterol synthesis is based on simple elements in the body. In the blood is transported in lipoproteins, and if the level rises and increases the risk of atherosclerosis. Typically for a person weighing 68 kg for the synthesis of cholesterol, 1 g per day. The extra day of cholesterol in the United States 200-300 mg. The body maintains a balance by the minimization of the total amount synthesized in the body, when the supply of cholesterol.
Cholesterol is also recycled, is eliminated by the liver via the bile into the digestive tract. Approximately 50% of the excreted cholesterol absorbed by the small intestine and reaches the bloodstream. Phytosterols compete with cholesterol absorption in the intestine and thus cholesterol. Cholesterol is a fat in the body in small quantities are needed. High levels of cholesterol in the blood can lead to conditions of coronary artery disease and angina pectoris. Nitrates are found to relieve angina. Most people have regular tests to draw blood cholesterol, triglycerides, which consist of the study, high-density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol.
Methods for increasing good cholesterol and lowering cholesterol in the blood cholesterol, including statins, fibrates, niacin and bile acid sequestrants. These drugs are not able to reverse the calcification of the coronary arteries are blocked when a heart attack. The two main types of cholesterol are high-density lipoprotein (HDL) and low density lipoprotein (LDL). For simplicity, the LDL cholesterol HDL the good cholesterol is known as long as the bad cholesterol. We can see that the bad cholesterol that is responsible for the formation of plaque in arteries and therefore the risk of heart attack increases. Transport of cholesterol good cholesterol in the other plate by hand and returned to the bloodstream for excretion by the liver.
Type
There are three main types of lipoproteins in fasting serum lipoproteins informed, low density (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL) found.
The first low-density lipoprotein (LDL) or bad cholesterol, and management
LDL or bad cholesterol comprises 60-70% of total serum cholesterol. It is important atherogenic lipoprotein-lowering therapy in high cholesterol are dangerous. Cholesterol deposits in artery walls, which calls for the formation of a hard substance, such as cholesterol plaque. This board is responsible for the hardening of the arteries, making them narrow and the process is called atherosclerosis. The liver not only produces and secretes LDL cholesterol into the blood, but also removes the blood. A large number of active receivers on the surface of the liver, which actively bind to molecules of LDL cholesterol and remove the blood. LDL receptor deficiency is associated with high levels of molecules in the blood.
Some benefits are known as reducing levels of bad cholesterol, for example, decay reduced the formation of new plaques in artery walls, removing existing plaques in the arteries, the veins are normal shape, preventing plaque rupture, formation of blood clots and possibly the risk of heart attack is easier. Several studies have shown that reducing the risk of heart attack by 25% for every 10% reduction in LDL cholesterol and is the decisive factor in the total cholesterol in the blood reached a safe area. A study of 4,000 people confirmed that the bad cholesterol and the risk of heart attack by 25% and 42% reduction in the statin. Is it viable is that the daily consumption of calories from fat to 30% and reduced the consumption of different types of food should be rich in carbohydrates, proteins, because the body that increases triglycerides, which are then stored as fat.
Foods high in saturated fat increases LDL-cholesterol in the blood. Fats can be classified as saturated and unsaturated. Saturated fats are readily available in meat, dairy products and certain vegetable oils, especially coconut oil, palm oil and cocoa available. Therapeutic lifestyle changes to reduce levels of bad cholesterol, regular exercise taken, losing weight and a diet low in saturated fat and cholesterol. When lifestyle changes, the desired results are not considered drugs. Statins are the drugs most effective in giving the best results at the level of bad cholesterol and reduces the risk of heart disease. Other drugs that can be used are gemfibrozin fibrates, such as cholestyramine, and ezetimibe Zetia. National Institutes of Health, the American Heart Association and the American College of Cardiology some guidelines to help medical experts for dealing with high cholesterol free.
Two high-density lipoprotein (LDL) or good cholesterol and its benefits
HDL or good cholesterol, prevent atherosclerosis by removing cholesterol from artery walls and their elimination by the liver. High levels of LDL cholesterol and HDL cholesterol are at lower risk of heart disease. Therefore, the levels maintained a healthy and happy and enjoy life. HDL cholesterol is 20-30% of total serum cholesterol. Because it reduces the risk of atherosclerosis reduces the amount should be checked occasionally. Heredity and diet have a major impact on the individual HDL, LDL and total cholesterol. Families with low levels of HDL have an increased risk of heart attack and vice versa. Lifestyle and other factors affecting HDL levels. HDL are low in people who smoke, obesity, physical inactivity and diabetes mellitus type II. HDL levels are higher in people who are thin, regular exercise and not smoking. Estrogens also increase HDL levels that women higher levels of HDL cholesterol than men.
LDL cholesterol is easier to raise HDL cholesterol. The reduction of LDL and HDL increases have a positive effect on the health of the individual. Previous researchers have a lot more about how the level of bad cholesterol, but with the progress of the investigation, it became clear that it is better to increase the levels of good cholesterol lowers bad cholesterol because it automatically is concentrated. Levels can be affected by weight reduction, regular exercise and increased consumption of niacin. Some studies suggest that statins and niacin, in combination with better results and women with high HDL lower risk of heart attack. The mean HDL levels in women must be between 50 to 55 mg dl / dl in men and mg / 40-50. Total cholesterol and HDL cholesterol may be useful to estimate the risk of atherosclerosis. An average ratio should be between 4-5.
Studies have shown that even a small increase in HDL cholesterol may reduce the risk of a heart attack. For each 1 mg / dl increase in HDL-cholesterol, reduces the risk of heart disease in 4.2%. However, the therapeutic lifestyle changes to help raise HDL levels. If these changes do not yield positive results after taking drugs. Regular aerobic exercise, losing weight and quitting smoking are useful for increasing HDL levels. Regular consumption of alcohol can help, such as one drink per day in this area, but many side effects alcohol consumption is related to the health of this criterion has been ignored. Effective drugs are gemfibrozil, estrogen and lower doses of statins. A new drug is the most successful and fenofibrate in reducing serum triglycerides.
Third triglycerides or lipoprotein of very low density lipoproteins (VLDL) and their effects or ugly
Lipoprotein cholesterol, triglycerides are ugly, that 10-15% of total serum cholesterol accounts. Cholesterol is produced by the liver and some VLDL remnants seem to promote atherosclerosis similar to LDL. Triglycerides are a type of fat transported to the tissues by blood. Most body fat consists of triglycerides. Serum triglycerides can be drawn from two sources. The first source is the food we eat, for example, when we eat a diet rich in fats in the intestine and enter some of them during the rest transported to the liver. The second source is the liver itself. When fats are absorbed in the liver, the fatty acids needed by fat cells and converts them into packets of triglycerides, which was later published as a fuel. There is some controversy about the fact that high levels of triglycerides are responsible for the disease or not.
Other clinical outcomes often with a high level of triglycerides in the blood pressure, obesity, diabetes, chronic kidney disease, liver and heart disease and hypothyroidism. Hereditary in certain high levels of triglycerides are people, and this condition has been identified as hypertriglyceridemia. The best known examples of hypertriglyceridemia mixed hypertriglyceridemia, familial hypertriglyceridemia and dysbetalipoproteinemia. Hypertriglyceridemia may also occur due to non-genetic factors such as obesity, alcohol abuse, diabetes mellitus, kidney disease and the use of estrogen-containing medications, such as the pill. Levels back to normal, without medication, with the help of a doctor. The first step was to treat hypertriglyceridemia involves the administration of a diet low in fat with reduced consumption of sweets, regular aerobic exercise, losing excess weight, alcohol and reduce snuff. In patients with diabetes mellitus, an effective control of blood glucose in the blood is necessary.
If necessary medications, statins, fibrates and niacin can be used. Fibrates not only reduce triglyceride levels, but also to increased levels of HDL and LDL particle size of molecules. Same task is performed by niacin, but decreases the rate of Lp (a) and cholesterol. Statins, on the other hand, lower triglycerides and LDL, but are not effective in raising HDL levels. A recently published drug fenofibrate has promising results in reducing the levels of triglycerides and LDL cholesterol and raise HDL levels, particularly in individuals with an optimal response, illustrated with fibrates. For some people, a combined dose of fenofibrate with a statin or fibrate necessary for best results.
Function
Cholesterol is needed for the creation and maintenance of membranes and modulates membrane fluidity over a wide range of physiological temperatures. The hydroxyl group on cholesterol molecule reacts with the polar headgroups of membrane phospholipids and sphingolipids, causing the membrane permeability for protons. Within the cell membrane, which also works in the performance of the cell transport, signaling and intracellular nerve. Cholesterol is also very important for the structure and function of invaginated caveolae and coated pit endocytosis. Recently it was suggested that cholesterol also plays a role in cell signaling processes, helping in the formation of lipid rafts in the plasma membrane. In many neurons, a myelin sheath rich in cholesterol is present, from compressed layers of the membrane-derived Schwann cells to aid in efficient nerve conduction. This layer also provides insulation. In cells, cholesterol serves as a precursor to a number of biochemical processes. In the liver, cholesterol in the bile, which is then stored in the gallbladder. The bile is rich in bile salts dissolve the active molecules of fat in the digestive tract and in the intestinal absorption of fat molecules and fat-soluble vitamins A, D, E and K. help is also an important precursor for the synthesis of vitamin D and steroid hormones.
Biosynthesis and regulation
All animal cells produce cholesterol, but production varies with the type of cells and organs. 20-25% of the daily production of cholesterol in the liver and the rest of the colon, adrenal glands and reproductive organs. The synthesis of cholesterol in the body starts with a molecule of acetyl-CoA and acetoacetyl-CoA from one molecule, which is hydrated to form the 3-hydroxy-3-methyl-CoA (HMG-CoA). HMG-CoA to mevalonate is formed is reduced by the enzyme HMG-CoA reductase to form. This step is irreversible and rate-limiting step in cholesterol synthesis. Mevalonate is formed, it is necessary to have a 3-isopentenyl pyrophosphate in three reactions are ATP. Mevalonate isopentenyl pyrophosphate is then decarboxylated form. Isopentenyl pyrophosphate and three molecules together to form farnesyl pyrophosphate in the presence of geranyl transferase. Two molecules of farnesyl pyrophosphate, squalene is in the endoplasmic reticulum to form and to the reaction catalyzed by squalene synthetase. Lanosterol cyclase Oxidosqualene converts squalene, ultimately leading to cholesterol. The regulatory mechanism of cholesterol and is used by Bloch and Feodor Lynen Konard, the Nobel Prize in Physiology or Medicine was awarded in 1964.
Cholesterol under the strict control of blood cholesterol, but the mechanisms involved in their homeostatic regulation partially understood. A higher intake of cholesterol results in a marked decrease in endogenous production, and vice versa. The main mechanism involved includes the detection of intracellular cholesterol to the protein (the protein binding of sterol regulatory element 1 and 2) SREBP from the endoplasmic reticulum. It binds cholesterol in the presence of this protein with two other proteins, ie, the SCAP (SREBP activation protein-splitting) and INSIG first or cholesterol decreases SREBP complex dissociates to INSIG-an PAP, so this complex at the entrance to the Golgi where SREBP is cleaved by proteases S1 and S2. These proteases are activated by SCAP when cholesterol levels fall. The cleaved SREBP migrates over to the nucleus as a transcription factor, and is then connected to the sterol regulatory element (SRE), the transcription of many genes promoting, for example, the interception of circulating blood volume LDL low-density lipoprotein (LDL) and increase of the body's production of cholesterol in the HMG-CoA reductase. Much of this route was developed by Dr. Michael S. Brown and Joseph L. Goldstein, Ph.D., in the year 1970, received the Nobel Prize for his work in 1985.
Cholesterol synthesis may be terminated if cholesterol is high. HMG-CoA reductase, contributes to both the cytosolic and membrane domains. The surface of the membrane is sensitive to signals that are required for removal. High levels of cholesterol results in a change in the state of oligomerization domain, making them more susceptible to destruction by the proteasome. The activity of this enzyme is also the phosphorylation of protein kinase activated by AMP are reduced. Cholesterol is only slightly soluble in water and can be dissolved in the aqueous blood, but moves at very low concentrations. Because cholesterol is not soluble in the blood, is transported to the movement in the lipoprotein complex, the exterior is composed of protein and lipid amphiphiles. Triglycerides and cholesterol esters are carried internally. Lipoprotein cholesterol is soluble in the blood and therefore lipoproteins are transported in different forms in chylomicrons say blood, very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) lipoprotein density lipoprotein (LDL) and high density lipoprotein performed (HDL).
The chylomicrons are transported to the less dense type of cholesterol molecules, whose shells are rich in apolipoprotein B-48, C and apolipoprotein E. They are fat, needed in the intestines, muscles and other tissues, fatty acids into energy. Cholesterol, not the muscles remain in the form of chylomicron remnants, which are then eliminated by the liver via the blood. Molecules are produced by VLDL triglyceride and cholesterol in the liver, not liver to produce bile acids necessary costs. These molecules contain apolipoprotein B100 and apolipoprotein E in the shell. While the distribution of the transport of blood vessels and take the IDL triglyceride molecules that have a high concentration of cholesterol. LDL molecules are the main carrier of cholesterol in the blood and each molecule contains about 1500 cholesterol esters. The shell of the LDL molecule contains a single molecule of apolipoprotein B100, which is recognized by LDL receptors in peripheral tissues. While the binding of apolipoprotein B100 and LDL receptors are located in many coated pits. LDL and its receptors are made by endocytosis, vesicles in the cell that fuses with lysosomes to lysosomal acid lipase, which hydrolyzes cholesterol esters to form. At this stage can be used for the cholesterol biosynthesis of the membrane and can be stored in the cell.
Protein synthesis of the LDL receptor is regulated by SREBP. If the cell has enough cholesterol, LDL receptor synthesis is blocked and no more cholesterol molecules in the cell. If the cell is the lack of LDL cholesterol receptors are formed. If this system is more LDL LDL receptor molecules was liberalized in the bloodstream, especially in the vicinity of the peripheral tissues. These molecules are oxidized and forms of macrophage foam cells contributes to the formation of atherosclerotic plaques on the walls of arteries causing a heart attack more. HDL molecules to participate in reverse cholesterol transport, as he returned to the liver for excretion. Cholesterol is susceptible to oxidation and can easily form oxysterol, such as derivatives of oxygen. Oxysterol can be generated by three main mechanisms of auto-oxidation, oxidation secondary to lipid peroxidation and the enzymatic oxidation of cholesterol metabolism. Oxysterol in the biosynthesis of bile acids, cholesterol and transport of various forms of regulation of transcription of the genes involved.
Cholesterol is oxidized by the liver into a variety of bile acids, which in turn, conjugated with glycine, taurine, glucuronic acid. A mixture of conjugated bile acids conjugated with two cholesterol from the liver is excreted in the bile. Approximately 95% of bile acids absorbed by the intestine, while the rest is lost in the stool. Excretion and reabsorption of bile acids are the basis of the enterohepatic circulation is essential for digestion and absorption of fats in the diet. In certain circumstances, cholesterol crystallizes, forming gallstones, especially in the gallbladder. Lecithin and bilirubin gallstones also occur are known, but their share is low. Every day, approximately 1 g of cholesterol is known as the colon, go into the food, the bile is the elimination of intestinal cells and can be metabolized by intestinal bacteria. Cholesterol is excreted primarily in a non-absorbable sterols coprostanol in stool. Cholesterol-lowering bacterium was isolated from human feces. Some derivatives of cholesterol known cholesteric liquid crystalline phase to produce. Cholesterol
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