Information AboutCholesterol |
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Cholesterol is a Sterol (a combination Steroid and Alcohol ), a Lipid found in the Cell Membrane s of all Body tissues, and is transported in the Blood Plasma of all Animal s. Because cholesterol is synthesized by all Eukaryote s, trace amounts of cholesterol are also found in membranes of Plant s and Fungi . The name originates from the Greek ''chole-'' ( Bile ) and ''stereos'' (solid), and the Chemical Suffix ''-ol'' for an alcohol, as researchers first identified cholesterol in solid form in Gallstone s in 1784 . Most of the cholesterol is synthesized by the body and some has dietary origin. Cholesterol is more abundant in tissues which either synthesize more or have more abundant densely-packed membranes, for example, the Liver , Spinal Cord , Brain , and Atheroma ta (arterial plaques). Cholesterol plays a central role in many Biochemical processes, but is best known for the association of Cardiovascular Disease with various Lipoprotein cholesterol transport patterns and High Levels Of Cholesterol in the blood. Cholesterol is insoluble in blood, but is transported in the circulatory system bound to one of the varieties of Lipoprotein , spherical particles which have an exterior composed mainly of water-soluble proteins. In recent years, the term "bad cholesterol" has been used to refer to cholesterol contained in LDL ( Low-density Lipoprotein ) which, according to the Lipid Hypothesis , is thought to have harmful actions, and "good cholesterol" to refer to cholesterol contained in HDL ( High-density Lipoprotein ), thought to have beneficial actions. PHYSIOLOGY Function Cholesterol is required to build and maintain (which is stored in the gallbladder and helps digest fats), and is also important for the metabolism of Fat Soluble Vitamins , including vitamins A , D , E and K . It is the major precursor for the synthesis of Vitamin D and of the various Steroid Hormone s (which include Cortisol and Aldosterone in the Adrenal Gland s, and the sex hormones Progesterone , the various Estrogen s, Testosterone , and derivatives). Recently, cholesterol has also been implicated in cell signalling processes, where it has been suggested that it forms Lipid Rafts in the Plasma Membrane . It also reduces the permeability of the plasma membrane to Hydrogen ions ( Proton s) and Sodium Ion s.Haines, TH. Do sterols reduce proton and sodium leaks through lipid bilayers? ''Prog Lipid Res'' 2001:40:299 – 324. PMID 11412894. Cholesterol is essential for the structure and function of invaginated Caveolae and clathrin-coated pits, including the caveolae-dependent Endocytosis and clathrin-dependent endocytosis. The role of cholesterol in caveolae-dependent and clathrin-dependent endocytosis can be investigated by using Methyl Beta Cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Synthesis and intake Cholesterol is required in the membrane of mammalian cells for normal cellular function, and is either synthesized in the Endoplasmic Reticulum , or derived from the diet, in which case it is delivered by the bloodstream in low-density lipoproteins. These are taken into the cell by Receptor -mediated Endocytosis in clathrin-coated pits, and then hydrolysed in lysosomes. Cholesterol is primarily synthesized from Acetyl CoA through the HMG-CoA Reductase Pathway in many Cells and Tissues . About 20 – 25% of total daily production (~1 G / Day ) occurs in the Liver ; other sites of higher synthesis rates include the Intestines , Adrenal Gland s and Reproductive Organ s. For a person of about 150 pounds (68 kg), typical total body content is about 35 G , typical daily internal production is about 1 g and typical daily dietary intake is 200 to 300 mg. Of the cholesterol input to the intestines via bile production, 92-97% is reabsorbed in the intestines and recycled via Enterohepatic Circulation . Konrad Bloch and Feodor Lynen shared the Nobel Prize In Physiology Or Medicine in 1964 for their discoveries concerning the mechanism and regulation of the cholesterol and Fatty Acid metabolism. Regulation Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the . When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the Golgi Apparatus , where SREBP is cleaved by S1P and S2P (site 1/2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a Transcription Factor to bind to the SRE (sterol regulatory element) of a number of genes to stimulate their Transcription . Among the genes transcribed are the LDL Receptor and HMG-CoA Reductase . The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase of endogenous production of cholesterol.1 A large part of this mechanism was clarified by Dr Michael S. Brown and Dr Joseph L. Goldstein in the 1970s. They received the Nobel Prize In Physiology Or Medicine for their work in 1985. The average amount of blood cholesterol varies with age, typically rising gradually until one is about 60 years old. There appear to be seasonal variations in cholesterol levels in humans, more, on average, in winter.2 Excretion Cholesterol is excreted from the Liver in Bile and reabsorbed from the intestines. Under certain circumstances, when more concentrated, as in the Gallbladder , it crystallises and is the major constituent of most Gallstone s, although Lecithin and Bilirubin gallstones also occur less frequently. Body fluids Cholesterol is minimally soluble in Water ; it cannot dissolve and travel in the water-based bloodstream. Instead, it is transported in the bloodstream by Lipoprotein s - protein "molecular-suitcases" that are water-soluble and carry cholesterol and Triglyceride s internally. The Apolipoprotein s forming the surface of the given lipoprotein particle determine from what cells cholesterol will be removed and to where it will be supplied. The largest lipoproteins, which primarily transport fats from the Intestinal Mucosa to the liver, are called Chylomicron s. They carry mostly fats in the form of Triglyceride s and cholesterol. In the Liver , chylomicron particles release triglycerides and some cholesterol. The liver converts unburned food metabolites into very low density lipoproteins (VLDL) and secretes them into plasma where they are converted to Low-density Lipoprotein (LDL) particles and non-esterified fatty acids, which can affect other body cells. In healthy individuals, the relatively few LDL particles are large. In contrast, large numbers of small dense LDL (sdLDL) particles are strongly associated with the presence of Atheroma tous disease within the arteries. For this reason, LDL is referred to as "bad cholesterol". The 1987 report of National Cholesterol Education Program, Adult Treatment Panels suggest the total blood cholesterol level should be: <200 mg/dl normal blood cholesterol, 200-239 mg/dl borderline-high, >240 mg/dl high cholesterol. High-density Lipoprotein (HDL) particles transport cholesterol back to the liver for excretion, but vary considerably in their effectiveness for doing this. Having large numbers of large HDL particles correlates with better health outcomes, and hence it is commonly called "good cholesterol". In contrast, having small amounts of large HDL particles is independently associated with Atheroma tous disease progression within the arteries. CLINICAL SIGNIFICANCE Hypercholesterolemia See Also: hypercholesterolemia Conditions with elevated concentrations of oxidized LDL particles, especially "small dense LDL" (sdLDL) particles, are associated with Atheroma formation in the walls of Arteries , a condition known as '' Atherosclerosis '', which is the principal cause of Coronary Heart Disease and other forms of Cardiovascular Disease . In contrast, HDL particles (especially large HDL) have been identified as a mechanism by which cholesterol and inflammatory mediators can be removed from atheroma. Increased concentrations of HDL correlate with lower rates of atheroma progressions and even regression. Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL are regarded as ''atherogenic'' (prone to cause atherosclerosis). Levels of these fractions, rather than the total cholesterol level, correlate with the extent and progress of atherosclerosis. Conversely, the total cholesterol can be within normal limits, yet be made up primarily of small LDL and small HDL particles, under which conditions atheroma growth rates would still be high. In contrast, however, if LDL particle number is low (mostly large particles) and a large percentage of the HDL particles are large, then atheroma growth rates are usually low, even negative, for any given total cholesterol concentration. Multiple human trials utilizing HMG-CoA reductase inhibitors, known as Statins , have repeatedly confirmed that changing lipoprotein transport patterns from unhealthy to healthier patterns significantly lowers cardiovascular disease event rates, even for people with cholesterol values currently considered low for adults. As a result, people with a history of cardiovascular disease may derive benefit from statins irrespective of their cholesterol levels,3 and in men without cardiovascular disease there is benefit from lowering abnormally high cholesterol levels ("primary prevention").4 Primary prevention in women in practiced only by extension of the findings in studies on men.5 The American Heart Association provides a set of guidelines for total (fasting) blood cholesterol levels and risk for heart disease: "About cholesterol" - American Heart Association However, as today's testing methods determine LDL ("bad") and HDL ("good") cholesterol separately, this simplistic view has become somewhat outdated. The desirable LDL level is considered to be less than 100 mg/dL (2.6 begin to develop is 35 mg/dL. Patients should be aware that most testing methods for LDL do not actually measure LDL in their blood, much less particle size. For cost reasons, LDL values have long been estimated using the Friedewald formula: cholesterol − HDL − 20% of the Triglyceride value = estimated LDL. The basis of this is that Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Ordinarily just the total, HDL, and triglycerides are actually measured. The VLDL is estimated as one-fifth of the triglycerides. It is important to fast for at least 8-12 hours before the blood test because the triglyceride level varies significantly with food intake. Given the well-recognized role of cholesterol in cardiovascular disease, it is surprising that some studies have shown an inverse correlation between cholesterol levels and mortality in subjects over 50 years of age — an 11% increase overall and 14% increase in CVD mortality per 1 mg/dL per year drop in cholesterol levels. In the Framingham Heart Study , the researchers attributed this phenomenon to the fact that people with severe chronic diseases or cancer tend to have below-normal cholesterol levels.6 This explanation is not supported by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all ages and women over 50 lower cholesterol levels with very low cholesterol were increasingly likely to die of cancer, liver diseases, and mental diseases. This result indicates that the low cholesterol effect occurs even among younger respondents, contradicting the previous assessment among cohorts of older people that this is a proxy or marker for frailty occurring with age.7 Hypocholesterolemia Abnormally low levels of cholesterol are termed '' Hypocholesterolemia ''. Research into the causes of this state is relatively limited, and while some studies suggest a link with Depression , Cancer and Cerebral Hemorrhage it is unclear whether the low cholesterol levels are a cause for these conditions or an Epiphenomenon {Link without Title} . FOOD SOURCES Cholesterol is found in animal fats: all food containing animal fats contains cholesterol; food not containing animal fats either contains no cholesterol or negligible amounts. Major dietary sources of cholesterol include eggs, beef and poultry. Nutrition and Your Health: Dietary Guidelines for Americans. Table E-18. Dietary Sources of Cholesterol Listed in Decreasing Order. Plants have trace amounts of cholesterol, so even a Vegan diet, which includes no animal foods, has traces of cholesterol. However, the amounts are very small. For example, to ingest the amount of cholesterol in one egg, one would need to drink about 9.6 litres (19.57 pounds) of pure peanut oil. "About cholesterol" - American Heart Association Behrman EJ, Gopalan V. Cholesterol and plants. ''J Chem Educ'' 2005;82:1791-1793. PDF Plant products (e.g. Flax Seed , Peanut ), also contain cholesterol-like compounds, Phytosterols , which are suggested to help lower Serum cholesterol.8 CHOLESTERIC LIQUID CRYSTALS Some cholesterol derivatives, (among other simple cholesteric lipids) are known to generate the Liquid Crystal line ''cholesteric phase''. The cholesteric phase is in fact a Chiral Nematic Phase , and changes colour when its temperature changes. Therefore, cholesterol derivatives are commonly used as temperature-sensitive Dye s, in liquid crystal Thermometer s and temperature-sensitive paints. SEE ALSO ADDITIONAL IMAGES |
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