query: What is cholesterol?

title: Cholesterol

text: acid biosynthesis, function as transport forms of cholesterol, and regulation of gene transcription. In biochemical experiments radiolabelled forms of cholesterol, such as tritiated-cholesterol are used. These derivatives undergo degradation upon storage and it is essential to purify cholesterol prior to use. Cholesterol can be purified using small Sephadex LH-20 columns. Cholesterol is oxidized by the liver into a variety of bile acids. These, in turn, are conjugated with glycine, taurine, glucuronic acid, or sulfate. A mixture of conjugated and nonconjugated bile acids, along with cholesterol itself, is excreted from the liver into the bile. Approximately 95% of the bile acids

title: Cholesterol

text: mainly into coprostanol, a nonabsorbable sterol that is excreted in the feces. A cholesterol-reducing bacterium origin has been isolated from human feces. Although cholesterol is a steroid generally associated with mammals, the human pathogen "Mycobacterium tuberculosis" is able to completely degrade this molecule and contains a large number of genes that are regulated by its presence. Many of these cholesterol-regulated genes are homologues of fatty acid β-oxidation genes, but have evolved in such a way as to bind large steroid substrates like cholesterol. Cholesterol binds to and affects the gating of a number of ion channels such as the nicotinic

title: Cholesterol

text: in 1964 for their discoveries concerning some of the mechanisms and methods of regulation of cholesterol and fatty acid metabolism. Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2). In the presence of cholesterol, SREBP is bound to two other proteins: SCAP

title: Cholesterol

text: trials are still needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, soya protein, plant sterols or stanols, especially in the case of familial hypercholesterolemia. As an isolated molecule, cholesterol is only minimally soluble in water; it dissolves into the (water-based) bloodstream only at exceedingly small concentrations. Instead, cholesterol is transported within lipoproteins, complex discoidal particles with exterior amphiphilic proteins and lipids, whose outward-facing surfaces are water-soluble and inward-facing surfaces are lipid-soluble; i.e. transport via emulsification. Triglycerides and cholesterol esters are carried internally. Phospholipids and cholesterol, being amphipathic, are transported in the monolayer

title: Cholesterol

text: are reabsorbed from the intestines, and the remainder are lost in the feces. The excretion and reabsorption of bile acids forms the basis of the enterohepatic circulation, which is essential for the digestion and absorption of dietary fats. Under certain circumstances, when more concentrated, as in the gallbladder, cholesterol crystallises and is the major constituent of most gallstones (lecithin and bilirubin gallstones also occur, but less frequently). Every day, up to 1 g of cholesterol enters the colon. This cholesterol originates from the diet, bile, and desquamated intestinal cells, and can be metabolized by the colonic bacteria. Cholesterol is converted

title: Cholesterol

text: domain senses signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteosome. This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein kinase. Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low. Animal fats are complex mixtures of triglycerides, with lesser amounts of both the phospholipids and cholesterol molecules from which all animal (and human) cell membranes are constructed. Since all

title: Cholesterol

text: surface of the lipoprotein particle. There are several types of lipoproteins in the blood. In order of increasing density, they are chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Lower protein/lipid ratios make for less dense lipoproteins. Cholesterol within different lipoproteins is identical, although some is carried as its native "free" alcohol form (the cholesterol-OH group facing the water surrounding the particles), while others as fatty acyl esters, known also as cholesterol esters, within the particles. Lipoprotein particles are organized by complex apolipoproteins, typically 80–100 different proteins per particle, which can be recognized and

title: Cholesterol

text: A-I and apolipoprotein B) and increased risk of cardiovascular disease, casting doubt on the cardioprotective role of "good cholesterol". Elevated cholesterol levels are treated with a strict diet consisting of low saturated fat, trans fat-free, low cholesterol foods, often followed by one of various hypolipidemic agents, such as statins, fibrates, cholesterol absorption inhibitors, nicotinic acid derivatives or bile acid sequestrants. Extreme cases have previously been treated with partial ileal bypass surgery, which has now been superseded by medication. Apheresis-based treatments are still used for very severe hyperlipidemias that are either unresponsive to treatment or require rapid lowering of blood lipids.

title: Cholesterol

text: bound by specific receptors on cell membranes, directing their lipid payload into specific cells and tissues currently ingesting these fat transport particles. Lipoprotein particles thus include a molecular addresses which play key roles in distribution and delivery of fats around the body in the water outside cells. Chylomicrons, the least dense cholesterol transport molecules, contain apolipoprotein B-48, apolipoprotein C, and apolipoprotein E (the principal cholesterol carrier in the brain) in their shells. Chylomicrons carry fats from the intestine to muscle and other tissues in need of fatty acids for energy or fat production. Unused cholesterol remains in more cholesterol-rich chylomicron

title: Cholesterol

text: dietary cholesterol as possible. Increased dietary intake of industrial trans fats is associated with an increased risk in all-cause mortality and cardiovascular diseases. Trans fats have been shown to correlate with reduced levels of HDL and increased levels of LDL. Based on this evidence, along with other claims implicating low HDL and high LDL levels in cardiovascular disease, many health authorities advocate reducing LDL-cholesterol through changes in diet in addition to other lifestyle modifications. The related studies which correlate trans fats, as well as saturated fats, with unhealthy serum cholesterol levels, have since been contested on numerous points. The most

title: Cholesterol

text: cortisol and aldosterone, as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives. The liver excretes cholesterol into biliary fluids, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K. All animal cells manufacture cholesterol, for both membrane structure and other uses, with relative production rates varying by cell type and organ function. About 80% of total daily cholesterol production occurs in the liver and the intestines; other sites

title: Cholesterol

text: Specially designed vegetarian experimental diets have been produced yielding upwards of 700 mg/day. Cholesterol, given that it composes about 30% of all animal cell membranes, is required to build and maintain membranes and modulates membrane fluidity over the range of physiological temperatures. The hydroxyl group of each cholesterol molecule interacts with the water molecules surrounding the membrane as do the polar heads of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases

title: Cholesterol

text: the previous assessment among cohorts of older people that this is a proxy or marker for frailty occurring with age. Although the vast majority of doctors and medical scientists consider that there is a link between cholesterol and atherosclerosis as discussed above, a 2014 meta-analysis concluded there is insufficient evidence to support the recommendation of high consumption of polyunsaturated fatty acids and low consumption of total saturated fats for cardiovascular health. Abnormally low levels of cholesterol are termed "hypocholesterolemia". Research into the causes of this state is relatively limited, but some studies suggest a link with depression, cancer, and cerebral

title: Cholesterol

text: the lipid hypothesis, since cholesterol (like all fat molecules) is transported around the body (in the water outside cells) inside lipoprotein particles, elevated cholesterol concentrations (hypercholesterolemia) potentially offer a lower cost way to estimate concentrations of LDL particles; possibly even low concentrations of functional HDL particles, both variations strongly associated with cardiovascular disease because LDL particles promote atheroma development in arteries (atherosclerosis). This atherosclerotic disease process, over decades, leads to myocardial infarction (heart attack), stroke, and peripheral vascular disease. Since higher blood LDL, especially higher LDL particle concentrations and smaller LDL particle size, contribute to this process more than the

title: Cholesterol-dependent cytolysin

text: successful binding. The non-polar hydrocarbon tail of cholesterol orients itself toward the polar center of the membrane lipid bilayer, while the 3-β-OH group is oriented closer to the ester bonds formed by the fatty acid chains, and glycerol backbones closer to the membrane surface. Even with the 3-β-OH group near the membrane surface, it is not very exposed compared to the phospholipid head groups. The availability of cholesterol at the membrane surface is dependent upon its interaction with other membrane components such as phospholipids and proteins; and the more cholesterol interacts with these components the less available it is to

title: Cholesterol-dependent cytolysin

text: though the presence of cholesterol is not required by all CDCs for binding. For example, Intermedilysin (ILY; TC# 1.C.12.1.5) secreted by "Streptococcus intermedius" will bind only to target membranes containing a specific protein receptor, independent of the presence of cholesterol, but cholesterol is required by intermedilysin (ILY; TC# 1.C.12.1.5) for pore formation. While the lipid environment of cholesterol in the membrane can affect toxin binding, the exact molecular mechanism that cholesterol regulates the cytolytic activity of the CDC is not fully understood. Once the pore is formed within the target cell membrane, the regulation of the intracellular environment and what

title: Cholesterol

text: 68 kg (150 lb) normally synthesizes about 1 gram (1,000 mg) per day, and his body contains about 35 g, mostly contained within the cell membranes. Typical daily cholesterol dietary intake for a man in the United States is 307 mg. Most ingested cholesterol is esterified, and esterified cholesterol is poorly absorbed. The body also compensates for any absorption of additional cholesterol by reducing cholesterol synthesis. For these reasons, cholesterol in food, seven to ten hours after ingestion, has little, if any effect on concentrations of cholesterol in the blood. However, during the first seven hours after ingestion of cholesterol,

title: Cholesterol

text: animal cells manufacture cholesterol, all animal-based foods contain cholesterol in varying amounts. Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, poultry, fish, and shrimp. Human breast milk also contains significant quantities of cholesterol. Plant cells do not manufacture cholesterol, and it is not found in plant foods. Some plant foods, such as avocado, flax seeds and peanuts, contain phytosterols, which compete with cholesterol for absorption in the intestines, reducing the absorption of both dietary and bile cholesterol. A typical diet contributes on the order of 0.2 gram of phytosterols, which is not enough to have a significant

title: Cholesterol

text: and cigarette smoking. Some cholesterol derivatives (among other simple cholesteric lipids) are known to generate the liquid crystalline "cholesteric phase". The cholesteric phase is, in fact, a chiral nematic phase, and it changes colour when its temperature changes. This makes cholesterol derivatives useful for indicating temperature in liquid-crystal display thermometers and in temperature-sensitive paints. Cholesterol has 256 stereoisomers that arise from its 8 stereocenters, although only two of the stereoisomers are of biochemical significance ("nat"-cholesterol and "ent"-cholesterol, for "natural" and "enantiomer", respectively), and only one occurs naturally ("nat"-cholesterol). Cholesterol Cholesterol (from the Ancient Greek "chole-" (bile) and "stereos" (solid), followed

title: Remnant cholesterol

text: disease in patients with normal total cholesterol. High plasma remnant cholesterol is associated with increased plasma triglyceride levels. Hypertriglyceridemia is characteristic of high plasma remnant cholesterol, but persons with high plasma triglycerides without high remnant cholesterol rarely have coronary artery disease. Remnant cholesterol has about twice the association with ischemic heart disease as LDL cholesterol. Although remnant cholesterol tends to be higher in people who are overweight (high body mass index, normal-weight persons with high remnant cholesterol tend to have a higher risk of myocardial infarction. Remnant cholesterol is associated with chronic inflammation, whereas LDL cholesterol is not. Remnant cholesterol

title: Remnant cholesterol

text: Remnant cholesterol Remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Stated another way, remnant cholesterol is all plasma cholesterol that is not LDL cholesterol or HDL cholesterol, which are triglyceride-rich lipoproteins. Nonetheless, remnant cholesterol is primarily chylomicron and VLDL from which most triglyceride has been removed, such that each remnant particle contains about 40 times more cholesterol than LDL. According to one study, high remnant cholesterol is more predictive of myocardial infarction than any other lipid particle. Remnant cholesterol is especially predictive of coronary artery

title: Cholesterol crystal

text: Impaired removal of cholesterol crystals from demyelinated nerves by macrophages is believed to be associated with multiple sclerosis, and this remyelination failure is particularly impaired in the elderly. Cholesterol crystal A cholesterol crystal is a solid, crystalline form of cholesterol found in gallstones and atherosclerosis. Gallstones occurring in industrialized societies typically contain more than 70-90% cholesterol by weight, much of which is crystalline. Cholesterol crystals are a hallmark of atherosclerosis, which is believed to be an early cause of atherosclerotic inflammation. Cholesterol phase transition from liquid to crystalline form is linked to inflammation. Cholesterol crystals are believed to induce inflammation

title: Cholesterol

text: form (via bile) into the digestive tract. Typically, about 50% of the excreted cholesterol is reabsorbed by the small intestine back into the bloodstream. Plants make cholesterol in very small amounts. Plants manufacture phytosterols (substances chemically similar to cholesterol), which can compete with cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol reabsorption. When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into the GI tract, an important protective mechanism. The intake of naturally occurring phytosterols, which encompass plant sterols and stanols, ranges between ~200–300 mg/day depending on eating habits.

title: The 8-Week Cholesterol Cure

text: Pressure without Prescription Drugs", which dealt with blood pressure. In October 1988 a lawsuit was filed by 16 plaintiffs against Kowalski and Harper & Row. The plaintiffs alleged that following the advice listed in the book caused them emotional and physical harm and that the book was not properly researched by its author or publisher. In the book Kowalski writes about his experiences with cholesterol and uses it to help recommend changes that readers can use to improve their cholesterol. It includes information about cholesterol and what foods people can eat to immediately reduce cholesterol, as well as what vitamins

title: Cholesterol crystal

text: Cholesterol crystal A cholesterol crystal is a solid, crystalline form of cholesterol found in gallstones and atherosclerosis. Gallstones occurring in industrialized societies typically contain more than 70-90% cholesterol by weight, much of which is crystalline. Cholesterol crystals are a hallmark of atherosclerosis, which is believed to be an early cause of atherosclerotic inflammation. Cholesterol phase transition from liquid to crystalline form is linked to inflammation. Cholesterol crystals are believed to induce inflammation by activation of the NLRP3 inflammasome. In addition to being a source of inflammation, cholesterol crystals are believed to cause mechanical injury by tearing tissue, causing plaque rupture.

title: Cholesterol

text: used for membrane biosynthesis or esterified and stored within the cell, so as to not interfere with the cell membranes. LDL receptors are used up during cholesterol absorption, and its synthesis is regulated by SREBP, the same protein that controls the synthesis of cholesterol "de novo", according to its presence inside the cell. A cell with abundant cholesterol will have its LDL receptor synthesis blocked, to prevent new cholesterol in LDL molecules from being taken up. Conversely, LDL receptor synthesis proceeds when a cell is deficient in cholesterol. When this process becomes unregulated, LDL molecules without receptors begin to appear

title: Cholesterol

text: sodium ions. Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolae and clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. The role of cholesterol in endocytosis of these types can be investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recent studies show that cholesterol is also implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane, which brings receptor proteins in close proximity with high concentrations of second messenger molecules. In multiple

title: Cholesterol

text: hemorrhage. In general, the low cholesterol levels seem to be a consequence, rather than a cause, of an underlying illness. A genetic defect in cholesterol synthesis causes Smith-Lemli-Opitz syndrome, which is often associated with low plasma cholesterol levels. Hyperthyroidism, or any other endocrine disturbance which causes upregulation of the LDL receptor, may result in hypocholesterolemia. The American Heart Association recommends testing cholesterol every 4–6 years for people aged 20 years or older. A separate set of American Heart Association guidelines issued in 2013 indicates that patients taking statin medications should have their cholesterol tested 4–12 weeks after their first dose

title: Cholesterol

text: Cholesterol Cholesterol (from the Ancient Greek "chole-" (bile) and "stereos" (solid), followed by the chemical suffix "-ol" for an alcohol) is an organic molecule. It is a sterol (or modified steroid), a type of lipid molecule, and is biosynthesized by all animal cells, because it is an essential structural component of all animal cell membranes. In addition to its importance for animal cell structure, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Cholesterol is the principal sterol synthesized by all animals. In vertebrates, hepatic cells typically produce the greatest amounts. It

title: Cholesterol

text: is absent among prokaryotes (bacteria and archaea), although there are some exceptions, such as "Mycoplasma", which require cholesterol for growth. François Poulletier de la Salle first identified cholesterol in solid form in gallstones in 1769. However, it was not until 1815 that chemist Michel Eugène Chevreul named the compound "cholesterine". Since cholesterol is essential for all animal life, each cell is capable of synthesizing it by way of a complex 37-step process, beginning with the mevalonate pathway and ending with a 19-step conversion of lanosterol to cholesterol. Furthermore, it can be absorbed directly from animal-based foods. A human male weighing

title: Cholesterol

text: hormones, in a process known as reverse cholesterol transport (RCT). Large numbers of HDL particles correlates with better health outcomes, whereas low numbers of HDL particles is associated with atheromatous disease progression in the arteries. Cholesterol is susceptible to oxidation and easily forms oxygenated derivatives called oxysterols. Three different mechanisms can form these: autoxidation, secondary oxidation to lipid peroxidation, and cholesterol-metabolizing enzyme oxidation. A great interest in oxysterols arose when they were shown to exert inhibitory actions on cholesterol biosynthesis. This finding became known as the “oxysterol hypothesis”. Additional roles for oxysterols in human physiology include their participation in bile

title: Cholesterol

text: statistically significant for both genders. Though this result was met with some skepticism, later studies and meta-analyses likewise demonstrated statistically significant (but smaller) reductions in all-cause and cardiovascular mortality, without significant heterogeneity by gender. The 1987 report of National Cholesterol Education Program, Adult Treatment Panels suggests the total blood cholesterol level should be: < 200 mg/dL normal blood cholesterol, 200–239 mg/dL borderline-high, > 240 mg/dL high cholesterol. The American Heart Association provides a similar set of guidelines for total (fasting) blood cholesterol levels and risk for heart disease: However, as today's testing methods determine LDL ("bad") and HDL ("good") cholesterol

title: Cholesterol 24-hydroxylase

text: Cholesterol 24-hydroxylase In enzymology, a cholesterol 24-hydroxylase () is an enzyme that catalyzes the chemical reaction The 4 substrates of this enzyme are cholesterol, NADPH, H, and O, whereas its 3 products are (24S)-24-hydroxycholesterol, NADP, and HO. The systematic name of this enzyme class is cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating). Other common names include cholesterol 24-monooxygenase, CYP46, CYP46A1, cholesterol 24S-hydroxylase, and cytochrome P450 46A1. This enzyme belongs to the highly conserved family of enzymes known as cytochrome P450s (CYP). Like many other cholesterol-targeting cytochrome P450s, Cholesterol-24 hydroxylase is a monooxygenase that hydroxylates the side-chain of cholesterol. Present mainly in the brain, this

title: Cholesterol

text: over 50 years of age, they found an 11% increase overall and 14% increase in cardiovascular disease mortality per 1 mg/dL per year drop in total cholesterol levels. The researchers attributed this phenomenon to the fact that people with severe chronic diseases or cancer tend to have below-normal cholesterol levels. This explanation is not supported by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all ages and women over 50 with very low cholesterol were likely to die of cancer, liver diseases, and mental diseases. This result indicates the low-cholesterol effect occurs even among younger respondents, contradicting

title: Cholesterol

text: There are several international guidelines on the treatment of hypercholesterolaemia. Multiple human trials using 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. Studies have also found that statins reduce atheroma progression. As a result, people with a history of cardiovascular disease may derive benefit from statins irrespective of their cholesterol levels (total cholesterol below 5.0 mmol/L [193 mg/dL]), and in men without cardiovascular disease, there is benefit from lowering abnormally high cholesterol

title: Cholesterol

text: cholesterol content of the HDL particles, LDL particles are often termed "bad cholesterol" because they have been linked to atheroma formation. On the other hand, high concentrations of functional HDL, which can remove cholesterol from cells and atheroma, offer protection and are sometimes referred to as "good cholesterol". These balances are mostly genetically determined, but can be changed by body build, medications, food choices, and other factors. 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

title: Cholesterol

text: acetylcholine receptor, GABA receptor, and the inward-rectifier potassium ion channel. Cholesterol also activates the estrogen-related receptor alpha (ERRα), and may be the endogenous ligand for the receptor. The constitutively active nature of the receptor may be explained by the fact that cholesterol is ubiquitous in the body. Inhibition of ERRα signaling by reduction of cholesterol production has been identified as a key mediator of the effects of statins and bisphosphonates on bone, muscle, and macrophages. On the basis of these findings, it has been suggested that the ERRα should be de-orphanized and classified as a receptor for cholesterol. According to

title: Cholesterol embolism

text: Cholesterol embolism Cholesterol embolism occurs when cholesterol is released, usually from an atherosclerotic plaque, and travels as an embolus in the bloodstream to lodge (as an embolism) causing an obstruction in blood vessels further away. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene of the extremities and sometimes renal failure; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. When the kidneys are involved, the disease is referred to as atheroembolic renal disease. The diagnosis usually involves biopsy (removing a tissue sample) from an affected organ. Cholesterol embolism is

title: Cholesterol 24-hydroxylase

text: a prime candidate for drug therapy for AD or other brain injuries. Cholesterol 24-hydroxylase In enzymology, a cholesterol 24-hydroxylase () is an enzyme that catalyzes the chemical reaction The 4 substrates of this enzyme are cholesterol, NADPH, H, and O, whereas its 3 products are (24S)-24-hydroxycholesterol, NADP, and HO. The systematic name of this enzyme class is cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating). Other common names include cholesterol 24-monooxygenase, CYP46, CYP46A1, cholesterol 24S-hydroxylase, and cytochrome P450 46A1. This enzyme belongs to the highly conserved family of enzymes known as cytochrome P450s (CYP). Like many other cholesterol-targeting cytochrome P450s, Cholesterol-24 hydroxylase is a monooxygenase

title: Cholesterol oxidase

text: Cholesterol oxidase In enzymology, a cholesterol oxidase () is an enzyme that catalyzes the chemical reaction Thus, the two substrates of this enzyme are cholesterol and O, whereas its two products are cholest-4-en-3-one and HO. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with oxygen as acceptor. The systematic name of this enzyme class is cholesterol:oxygen oxidoreductase. Other names in common use include cholesterol- O2 oxidoreductase, 3beta-hydroxy steroid oxidoreductase, and 3beta-hydroxysteroid:oxygen oxidoreductase. This enzyme participates in bile acid biosynthesis. The substrate-binding domain found in some bacterial cholesterol oxidases is composed of

title: Cholesterol absorption inhibitor

text: then be absorbed by the intestinal enterocyte. Once absorbed by the enterocyte, cholesterol is reassembled into intestinal lipoproteins called chylomicrons. These chylomicrons are then secreted into the lymphatics and circulated to the liver. These cholesterol particles are then secreted by the liver into the blood as VLDL particles, precursors to LDL. As a class, cholesterol absorption inhibitors block the uptake of micellar cholesterol, thereby reducing the incorporation of cholesterol esters into chylomicron particles. By reducing the cholesterol content in chylomicrons and chylomicron remnants, cholesterol absorption inhibitors effectively reduce the amount of cholesterol that is delivered back to the liver. The

title: Cholesterol

text: continues to lose triacylglycerols in the bloodstream until they become LDL molecules, with the highest concentration of cholesterol within them. LDL particles are the major blood cholesterol carriers. Each one contains approximately 1,500 molecules of cholesterol ester. LDL molecule shells contain just one molecule of apolipoprotein B100, recognized by LDL receptors in peripheral tissues. Upon binding of apolipoprotein B100, many LDL receptors concentrate in clathrin-coated pits. Both LDL and its receptor form vesicles within a cell via endocytosis. These vesicles then fuse with a lysosome, where the lysosomal acid lipase enzyme hydrolyzes the cholesterol esters. The cholesterol can then be

title: Reverse cholesterol transport

text: is carried to the liver to release all the esterified cholesterol into the liver. Reverse cholesterol transport Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream. Cholesterol from non-hepatic peripheral tissues is transferred to HDL by the ABCA1 (ATP-binding cassette transporter). Apolipoprotein A1 (ApoA-1), the major protein component of HDL, acts as an acceptor, and the phospholipid component of HDL acts as a sink for the mobilised cholesterol. The cholesterol is converted to cholesteryl esters by the enzyme LCAT

title: Cholesterol absorption inhibitor

text: Cholesterol absorption inhibitor Cholesterol absorption inhibitors are a class of compounds that prevents the uptake of cholesterol from the small intestine into the circulatory system. Most of these molecules are monobactams but show no antibiotic activity. An example is ezetimibe (SCH 58235) Another example is Sch-48461. The "Sch" is for Schering-Plough, where these compounds were developed. Phytosterols are also cholesterol absorption inhibitors. There are two sources of cholesterol in the upper intestine: dietary (from food) and biliary (from bile). Dietary cholesterol, in the form of lipid emulsions, combines with bile salts, to form bile salt micelles from which cholesterol can

title: Reverse cholesterol transport

text: Reverse cholesterol transport Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream. Cholesterol from non-hepatic peripheral tissues is transferred to HDL by the ABCA1 (ATP-binding cassette transporter). Apolipoprotein A1 (ApoA-1), the major protein component of HDL, acts as an acceptor, and the phospholipid component of HDL acts as a sink for the mobilised cholesterol. The cholesterol is converted to cholesteryl esters by the enzyme LCAT (lecithin-cholesterol acyltransferase). The cholesteryl esters can be transferred, with the help of CETP (cholesterylester

title: Cholesterol 24-hydroxylase

text: enzyme works to convert cholesterol from degraded neurons into 24S-hydroxycholesterol to allow for the elimination of cholesterol from the brain. Because the highly aliphatic cholesterol is normally unable to pass the blood-brain barrier, Cholesterol-24 hydroxylase is required to convert cholesterol into the more polar 24S-hydroxycholesterol to allow for passage into the bloodstream, where it is then carried to the liver for degradation. This enzyme has also been found in insignificant quantities in the retina, where it serves a similar (but limited) function of catalyzing the hydroxylation of cholesterol for cholesterol-elimination from the eye. Genetic cloning of encoding gene (CYP46A1) was

title: Cholesterol

text: layers, cholesterol and phospholipids, both electrical insulators, can facilitate speed of transmission of electrical impulses along nerve tissue. For many neuron fibers, a myelin sheath, rich in cholesterol since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses. Demyelination (loss of some of these Schwann cells) is believed to be part of the basis for multiple sclerosis. Within cells, cholesterol is also a precursor molecule for several biochemical pathways. For example, it is the precursor molecule for the synthesis of vitamin D and all steroid hormones, including the adrenal gland hormones

title: Cholesterol absorption inhibitor

text: reduced delivery of cholesterol to the liver increases hepatic LDL receptor activity and thereby increases clearance of circulating LDL. The net result is a reduction in circulating LDL particles. Managing cholesterol at the site of absorption is an increasingly popular strategy in the treatment of hypercholesterolemia . Cholesterol absorption inhibitors are known to have a synergistic effect when combined a class of antihyperlipidemics called statins, to achieve an overall serum cholesterol target. For statin-resistant or statin-sensitive populations that are characterized by low one-year compliance rates, such a combination therapy is proving to be especially effective . Cholesterol absorption inhibitor Cholesterol

title: Cholesterol

text: and then every 3–12 months thereafter. A blood sample after 12-hour fasting is taken by a doctor, or a home cholesterol-monitoring device is used to measure a lipid profile, an approach used to estimate a person's lipoproteins, the vastly more important issue because lipoproteins have always been concordant with outcomes though the lipid profile is commonly discordant LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study. The lipid profile measures: (a) total cholesterol, (b) cholesterol associated with HDL (i.e. Higher Density {than water} Lipids-transported-within-proteins) particles ("which can regress arterial disease"), (c) triglycerides and (d) (by

title: Cholesterol embolism

text: increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. If vasculitis is suspected, complement levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system. Complement levels are frequently reduced in cholesterol embolism, limiting the use of this test in the distinction between vasculitis and cholesterol embolism. The microscopic examination of tissue (histology) gives the definitive diagnosis. The diagnostic histopathologic finding is intravascular cholesterol crystals, which are seen as cholesterol clefts in routinely

title: Cholesterol 24-hydroxylase

text: reduce mRNA levels of the following cholesterol synthesis enzymes: HMG CoA reductase, squalene synthase, and FPP synthase. Variable expression of cholesterol-24 hydroxylase has been linked to the onset of Alzheimer's Disease (AD) in humans. Studies have shown that in AD patients, there is significant decreased expression of cholesterol-24 hydroxylase in neurons. As a result, there is a marked increase of cholesterol in the brain tissue, consistent with the trend observed in AD patients. Neuron degradation in AD has often been attributed to the imbalance in cholesterol homeostasis, and many scientist hypothesize that the lowered expression of cholesterol-24 hydroxylase may be

title: Cholesterol 24-hydroxylase

text: an oxyferryl intermediate to hydroxylate cholesterol. The oxyferryl radical takes the hydrogen from carbon-24 to create an alkyl radical intermediate. The cholesterol alkyl radical then combines with the activated oxygen on the heme to create 24S-hydroxycholesterol. Cholesterol-24 hydroxylase contributes to brain cholesterol homeostasis by hydroxylating cholesterol at carbon-24 to 24S-hydroxycholesterol to allow for elimination of cholesterol from the brain to the liver. Only around 6–7 mg of cholesterol, however, are hydroxylated by this enzyme on a daily basis, suggesting the existence of alternative functions – presently unknown. "In vitro" experiments have shown that it is also capable of further metabolizing

title: Cholesterol

text: in the blood. These LDL molecules are oxidized and taken up by macrophages, which become engorged and form foam cells. These foam cells often become trapped in the walls of blood vessels and contribute to atherosclerotic plaque formation. Differences in cholesterol homeostasis affect the development of early atherosclerosis (carotid intima-media thickness). These plaques are the main causes of heart attacks, strokes, and other serious medical problems, leading to the association of so-called LDL cholesterol (actually a lipoprotein) with "bad" cholesterol. HDL particles are thought to transport cholesterol back to the liver, either for excretion or for other tissues that synthesize

title: Cholesterol embolism

text: 3.4% of a large autopsy series of older individuals with severe atherosclerosis of the aorta. Cholesterol embolism Cholesterol embolism occurs when cholesterol is released, usually from an atherosclerotic plaque, and travels as an embolus in the bloodstream to lodge (as an embolism) causing an obstruction in blood vessels further away. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene of the extremities and sometimes renal failure; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. When the kidneys are involved, the disease is referred to as atheroembolic renal disease. The

title: Cholesterol-dependent cytolysin

text: its target membrane requires the recognition of cholesterol or in the case of intermedilysin (ILY; TC# 1.C.12.1.5), the recognition of CD59 membrane-anchored protein. The recognition of cholesterol provides specificity for eukaryotic cells and the specificity for the glycosylphosphatidylinositol-anchored protein CD59 provides specificity for human cells. Even though cholesterol is not required for intermedilysin (ILY) to bind to a target cell, the presence of cholesterol is required for pore formation by all CDC. CDC are sensitive to both oxygen and cholesterol. Toxins isolated-form culture supernatants were inactivated once exposed to oxygen after being pre-incubated with cholesterol. CDC are also pH-sensitive. A

title: Cholesterol

text: is estimated using the Friedewald formula (or a variant): estimated LDL = [total cholesterol] − [total HDL] − [estimated VLDL]. VLDL can be calculated by dividing total triglycerides by five. Direct LDL measures are used when triglycerides exceed 400 mg/dL. The estimated VLDL and LDL have more error when triglycerides are above 400 mg/dL. Given the well-recognized role of cholesterol in cardiovascular disease, some studies have shown an inverse correlation between cholesterol levels and mortality. A 2009 study of patients with acute coronary syndromes found an association of hypercholesterolemia with better mortality outcomes. In the Framingham Heart Study, in subjects

title: Cholesterol

text: on health is still larger in older people. 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. Recently, a "post hoc" analysis of the IDEAL and the EPIC prospective studies found an association between high levels of HDL cholesterol (adjusted for apolipoprotein

title: Cholesterol

text: 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. A 2007 study pooling data on almost 900,000 subjects in 61 cohorts demonstrated that blood total cholesterol levels have an exponential effect on cardiovascular and total mortality, with the association more pronounced in younger subjects. Still, because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol

title: Cholesterol

text: membrane packing, which both alters membrane fluidity and maintains membrane integrity so that animal cells do not need to build cell walls (like plants and most bacteria). The membrane remains stable and durable without being rigid, allowing animal cells to change shape and animals to move. The structure of the tetracyclic ring of cholesterol contributes to the fluidity of the cell membrane, as the molecule is in a "trans" conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol also reduces the permeability of the plasma membrane to neutral solutes, hydrogen ions, and

title: Cholesterol

text: a calculation and assumptions) cholesterol carried by LDL (i.e. Lower Density {than water} Lipids-transported-within-proteins) particles ("which drive arterial disease"). It is recommended to test cholesterol at least every five years if a person has total cholesterol of 5.2 mmol/L or more (200+ mg/dL), or if a man over age 45 or a woman over age 50 has HDL-C values less than 1 mmol/L (40 mg/dL), or there are other drivers heart disease and stroke. Additional drivers of heart disease include diabetes mellitus, hypertension (or use of anti-hypertensive medication), low HDL level, family history of coronary artery disease (CAD) and hypercholesterolemia,

title: Cholesterol embolism

text: made confidently based on clinical criteria. Treatment of an episode of cholesterol emboli is generally symptomatic, i.e. it deals with the symptoms and complications but cannot reverse the phenomenon itself. In kidney failure resulting from cholesterol crystal emboli, statins (medication that reduces cholesterol levels) have been shown to halve the risk of requiring hemodialysis. The phenomenon of embolisation of cholesterol was first recognized by the Danish pathologist Dr. Peter Ludvig Panum and published in 1862. Further evidence that eroded atheroma was the source of emboli came from American pathologist Dr. Curtis M. Flory, who in 1945 reported the phenomenon in

title: Cholesterol 25-hydroxylase

text: Cholesterol 25-hydroxylase In enzymology, a cholesterol 25-hydroxylase () is an enzyme that catalyzes the chemical reaction The 3 substrates of this enzyme are cholesterol, an electron acceptor AH, and O, whereas its 3 products are 25-hydroxycholesterol (25HC), the reduction product A, and HO. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derive from O miscellaneous. The systematic name of this enzyme class is cholesterol, hydrogen-donor:oxygen oxidoreductase (25-hydroxylating). This enzyme is also called cholesterol 25-monooxygenase. Transcripts for this enzyme

title: Cholesterol 24-hydroxylase

text: 24S-hydroxycholesterol into 24,25- and 24,27-dihydroxycholesterols. Cholesterol-24 hydroxylase has a variety of possible substrates, including: elongated steroid chains, cholesterol derivatives, and a variety of drug candidates. As such, it is also likely that it plays a role in lipid metabolism in the brain beyond cholesterol breakdown. Because 24S-hydroxycholesterol (main product of this enzyme) is a major activator of oxysterol liver X receptors (LXR), it is possible that cholesterol-24 hydroxylase may play an indirect regulatory role in the metabolism of lipids in the liver. 24S-hydroxycholesterol also regulates the rate of cholesterol synthesis in the brain, with high levels of 24S-hydroxycholesterol shown to

title: Cholesterol 24-hydroxylase

text: region, known as the B'-C loop, has a series of 5 residues (residues 116-120) unique to cholesterol-24 hydroxylase that contribute to the positioning of the cholesterol molecule within the active site. A single cholesterol molecule takes up the entirety of the active site, with the aliphatic tail of the cholesterol held in place by interactions with the following hydrophobic residues: Phe-121, Val-126, Ile-301, Ala-302, Ala-367, Thr-475. The active site is accessed via a single entrance created by two helices (B' and F) and the β1-sheet. There are no known allosteric regulatory sites. Like all other cytochrome P450s, cholesterol-24 hydroxylase utilizes

title: Cholesterol-dependent cytolysin

text: interact with extramembranous molecules. Some factors that affect cholesterols availability are size of the polar head groups and the ability of the phospholipid to hydrogen bond with the 3-β-OH group of cholesterol. Cholesterol associates with phospholipids, forming a stoichiometric complex and contributes to membrane fluidity. If cholesterol concentration exceeds a certain point, free cholesterol will begin to precipitate out of the membrane. The binding and pore formation of CDC will occur when the concentration of cholesterol exceeds the association capacity of the phospholipids, allowing the excess cholesterol to associate with the toxin. The presence of cholesterol aggregates in an aqueous

title: Cholesterol 7 alpha-hydroxylase

text: Cholesterol 7 alpha-hydroxylase Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the "CYP7A1" gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis. The inhibition of cholesterol 7-alpha-hydroxylase (CYP7A1) represses bile acid biosynthesis. Sequence comparisons indicated a huge similarity between cytochromes P450 identified in man and bacteria, and suggested that the superfamily Cytochrome P450 first originated from a common ancestral

title: Lecithin cholesterol acyltransferase deficiency

text: opacification. It rarely presents with other findings, although, atherosclerosis, hepatomegaly, splenomegaly, and lymphadenopathy can occur. Carlson and Philipson found that the disease was named so because the cornea of the eye was so opaque or cloudy with dots of cholesterol that it resembled a boiled fish. If an individual only carry one copy of the mutated gene, they typically do not show symptoms. A deficiency of LCAT causes accumulation of unesterified cholesterol in certain body tissues. Cholesterol effluxes from cells as free cholesterol and is transported in HDL as esterified cholesterol. LCAT is the enzyme that esterifies the free cholesterol

title: Cholesterol oxidase

text: an eight-stranded mixed beta-pleated sheet and six alpha-helices. This domain is positioned over the isoalloxazine ring system of the FAD cofactor bound by the FAD-binding domain and forms the roof of the active site cavity, allowing for catalysis of oxidation and isomerisation of cholesterol to cholest-4-en-3-one. As of late 2007, 14 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , , , , , , and . Cholesterol oxidase In enzymology, a cholesterol oxidase () is an enzyme that catalyzes the chemical reaction Thus, the two substrates of

title: Cholesterol

text: HMG-CoA reductase leads to an increase of endogenous production of cholesterol. A large part of this signaling pathway was clarified by Dr. Michael S. Brown and Dr. Joseph L. Goldstein in the 1970s. In 1985, they received the Nobel Prize in Physiology or Medicine for their work. Their subsequent work shows how the SREBP pathway regulates expression of many genes that control lipid formation and metabolism and body fuel allocation. Cholesterol synthesis can also be turned off when cholesterol levels are high. HMG-CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane

title: Cholesterol embolism

text: people with severe atherosclerosis of the large arteries such as the aorta. In the other 75% it is a complication of medical procedures involving the blood vessels, such as vascular surgery or angiography. In coronary catheterization, for instance, the incidence is 1.4%. Furthermore, cholesterol embolism may develop after the commencement of anticoagulants or thrombolytic medication that decrease blood clotting or dissolve blood clots, respectively. They probably lead to cholesterol emboli by removing blood clots that cover up a damaged atherosclerotic plaque; cholesterol-rich debris can then enter the bloodstream. Findings on general investigations (such as blood tests) are not specific for

title: Cholesterol 7 alpha-hydroxylase

text: and thereafter, results of many cloning studies have revealed a large number of different enzymes. Advances in molecular biology and genomics facilitated the biochemical characterisation of individual P450 enzymes: Cholesterol 7 alpha hydroxylase consists of 491 amino acids, which on folding forms 23 alpha helices and 26 beta sheets. Cholesterol 7 alpha-hydroxylase is a cytochrome P450 heme enzyme that oxidizes cholesterol in the position 7 using molecular oxygen. It is an oxidoreductase. CYP7A1 is located in the endoplasmic reticulum (ER) and is important for the synthesis of bile acid and the regulation of cholesterol levels. Cholesterol 7 alpha-hydroxylase is the

title: Cholesterol 24-hydroxylase

text: that polymorphisms in the encoding gene for cholesterol-24 hydroxylase have an established positive correlation with AD onset, other publications did not find such an association. Increased expression of cholesterol-24 hydroxylase has also been observed in patients of traumatic brain injury, leading to decreased levels of cholesterol in the plasma membrane. This is hypothesized to be the brain’s typical response to injury. Cholesterol-24 hydroxylase is easily inhibited by many drugs due to its broad substrate specificity. It has been shown to metabolize Bufuralol, progesterone, Dextromethorphan, methoxyresorufin, cortisol, Diclofenac, Phenacetin, and testosterone. The ability for inhibition by various xenobiotics makes this enzyme

title: Cholesterol

text: impact on blocking cholesterol absorption. Phytosterols intake can be supplemented through the use of phytosterol-containing functional foods or dietary supplements that are recognized as having potential to reduce levels of LDL-cholesterol. Some supplemental guidelines have recommended doses of phytosterols in the 1.6–3.0 grams per day range (Health Canada, EFSA, ATP III, FDA). A recent meta-analysis demonstrating a 12% reduction in LDL-cholesterol at a mean dose of 2.1 grams per day. However, the benefits of a diet supplemented with phytosterols have been questioned. In 2016, the United States Department of Agriculture Dietary Guidelines Advisory Committee recommended that Americans eat as little

title: Cholesterol embolism

text: processed tissue (embedded in paraffin wax). The cholesterol crystals may be associated with macrophages, including giant cells, and eosinophils. The sensitivity of small core biopsies is modest, due to sampling error, as the process is often patchy. Affected organs show the characteristic histologic changes in 50-75% of the clinically diagnosed cases. Non-specific tissue findings suggestive of a cholesterol embolization include ischemic changes, necrosis and unstable-appearing complex atherosclerotic plaques (that are cholesterol-laden and have a thin fibrous cap). While biopsy findings may not be diagnostic, they have significant value, as they help exclude alternate diagnoses, e.g. vasculitis, that often cannot be

title: Cholesterol-dependent cytolysin

text: tissue. Cholesterol-dependent cytolysin The Thiol-activated Cholesterol-dependent Cytolysin (CDC) family (TC# 1.C.12) is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs are secreted as water-soluble monomers of 50-70 kDa, that when bound to the target cell, form a circular homo-oligomeric complex containing as many as 40 (or more) monomers. Through multiple conformational changes, the β-barrel transmembrane structure (~250 Å in diameter depending on the toxin) is formed and inserted into the target cell membrane. The presence of cholesterol in the target membrane is required for pore

title: Cholesterol-dependent cytolysin

text: Cholesterol-dependent cytolysin The Thiol-activated Cholesterol-dependent Cytolysin (CDC) family (TC# 1.C.12) is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs are secreted as water-soluble monomers of 50-70 kDa, that when bound to the target cell, form a circular homo-oligomeric complex containing as many as 40 (or more) monomers. Through multiple conformational changes, the β-barrel transmembrane structure (~250 Å in diameter depending on the toxin) is formed and inserted into the target cell membrane. The presence of cholesterol in the target membrane is required for pore formation,

title: Cholesterol 7alpha-monooxygenase

text: Cholesterol 7alpha-monooxygenase In enzymology, a cholesterol 7alpha-monooxygenase () is an enzyme that catalyzes the chemical reaction The 4 substrates of this enzyme are cholesterol, NADPH, H, and O, whereas its 3 products are 7-alpha-hydroxycholesterol, NADP, and HO. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and incorporation of one atom o oxygen into the other donor. The systematic name of this enzyme class is cholesterol,NADPH:oxygen oxidoreductase (7alpha-hydroxylating). Other

title: Cholesterol 7 alpha-hydroxylase

text: mediated through the inhibition of transcription of this enzyme. This inhibition leads to more cholesterol in the bile, which is the body's only route of cholesterol excretion. This also increases the risk of cholesterol gallstone formation. Inhibition of CYP7A1 is thought to be involved in or responsible for the hepatotoxicity associated with ketoconazole. The levorotatory enantiomer of ketoconazole, levoketoconazole, shows 12-fold reduced potency in inhibition of this enzyme, and is under development for certain indications (e.g., Cushing's syndrome) as a replacement for ketoconazole with reduced toxicity and improved tolerability and safety. Cholesterol 7 alpha-hydroxylase Cholesterol 7 alpha-hydroxylase also known as

title: Cholesterol

text: of higher synthesis rates include adrenal glands, and reproductive organs. Synthesis within the body starts with the mevalonate pathway where two molecules of acetyl CoA condense to form acetoacetyl-CoA. This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. Production of mevalonate is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for statins (a class of cholesterol lowering drugs). Mevalonate is finally converted to isopentenyl pyrophosphate (IPP) through two phosphorylation steps and one decarboxylation step

title: Cholesterol

text: separately, this simplistic view has become somewhat outdated. The desirable LDL level is considered to be less than 130 mg/dL (2.6 mmol/L), although a newer upper limit of 70 mg/dL (1.8 mmol/L) can be considered in higher-risk individuals based on some of the above-mentioned trials. A ratio of total cholesterol to HDL—another useful measure—of far less than 5:1 is thought to be healthier. Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Usually, only the total, HDL, and triglycerides are measured. For cost reasons, the VLDL is usually estimated as one-fifth of the triglycerides and the LDL

title: Cholesterol 7alpha-monooxygenase

text: names in common use include cholesterol 7alpha-hydroxylase, and CYP7A1. This enzyme participates in bile acid biosynthesis and ppar signaling pathway. It employs one cofactor, heme. Cholesterol 7alpha-monooxygenase In enzymology, a cholesterol 7alpha-monooxygenase () is an enzyme that catalyzes the chemical reaction The 4 substrates of this enzyme are cholesterol, NADPH, H, and O, whereas its 3 products are 7-alpha-hydroxycholesterol, NADP, and HO. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as

title: Cholesterol-dependent cytolysin

text: to begin the process of oligomerization into the prepore complex. The phospholipid composition of a cell membrane affects the arrangement of cholesterol within the membrane and the ability for CDC to bind and initiate pore-formation. For example, perfringolysin O will preferentially bind to cholesterol-rich membranes composed mainly of phospholipids containing 18-carbon acyl chains. Lipids having a conical molecular shape alter the energetic state of membrane cholesterol, augmenting the interaction of the sterol with the cholesterol-specific cytolysin. Since high cholesterol concentrations are required for CDC binding/pore-formation, it was thought that CDC would associate with lipid rafts. A later study showed that

text: reported cases. Lecithin cholesterol acyltransferase deficiency Lecithin cholesterol acyltransferase deficiency (LCAT deficiency) is a disorder of lipoprotein metabolism. The disease has two forms: Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency. Lecithin cholesterol acyltransferase catalyzes the formation of cholesterol esters in lipoproteins. Symptoms of the familial form include visual impairment caused by diffuse corneal opacities, target cell hemolytic anemia, and renal failure. Less common symptoms include atherosclerosis, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), and lymphadenopathy. Fish-eye disease is less severe and most commonly presents with impaired vision due

text: Lecithin cholesterol acyltransferase deficiency Lecithin cholesterol acyltransferase deficiency (LCAT deficiency) is a disorder of lipoprotein metabolism. The disease has two forms: Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency. Lecithin cholesterol acyltransferase catalyzes the formation of cholesterol esters in lipoproteins. Symptoms of the familial form include visual impairment caused by diffuse corneal opacities, target cell hemolytic anemia, and renal failure. Less common symptoms include atherosclerosis, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), and lymphadenopathy. Fish-eye disease is less severe and most commonly presents with impaired vision due to corneal

title: Cholesterol

text: remnants, and taken up from here to the bloodstream by the liver. VLDL molecules are produced by the liver from triacylglycerol and cholesterol which was not used in the synthesis of bile acids. These molecules contain apolipoprotein B100 and apolipoprotein E in their shells, and are degraded by lipoprotein lipase on the blood vessel wall to IDL. Blood vessels cleave and absorb triacylglycerol from IDL molecules, increasing the concentration of cholesterol. IDL molecules are then consumed in two processes: half is metabolized by HTGL and taken up by the LDL receptor on the liver cell surfaces, while the other half

title: Cholesterol

text: that requires ATP. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is converted to cholesterol through a 19-step process. The final 19 steps to cholesterol contain NADPH and oxygen to help oxidize methyl groups for removal of carbons, mutases to move alkene groups, and NADH to help reduce ketones. Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine

title: Cholesterol total synthesis

text: , in 2002 by Jiang & Covey and again in 2008 by Rychnovsky and Belani . Cholesterol is a tetracyclic alcohol and a type of sterol. Added to the sterol frame with the alcohol group at position 3 are 2 methyl groups at carbon positions 10 and 13 and a 2-isooctyl group at position 17. The molecule is unsaturated at position 5,6 with an alkene group. The total number of stereocenters is 8. The unnatural cholesterol molecule that has also been synthesized is called ent-cholesterol. The Robinson synthesis is an example of a so-called relay synthesis. As many of the

title: Reverse cholesterol transport

text: transfer protein) in exchange for triglycerides, to other lipoproteins (such as LDL and VLDL), and these lipoproteins can be taken up by secreting unesterified cholesterol into the bile or by converting cholesterol to bile acids. Uptake of HDL is mediated by hepatic lipase, a special form of lipoprotein lipase found only in the liver. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of HDL in women. Discoidal (Nascent) HDL: When the HDL molecule is cholesterol rich, it's shape is changed into more spherical and it becomes less dense (HDL 2) This

title: Cholesterol side-chain cleavage enzyme

text: Cholesterol side-chain cleavage enzyme Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones. P450scc is a member of the cytochrome P450 superfamily of enzymes (family 11, subfamily A, polypeptide 1). The gene name is CYP11A1. The systematic name of this enzyme class is cholesterol,reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving). Other names include: The highest level of the cholesterol side-chain

title: Cholesterol

text: (SREBP cleavage-activating protein) and INSIG-1. When cholesterol levels fall, INSIG-1 dissociates from the SREBP-SCAP complex, which allows the complex to migrate to the Golgi apparatus. Here SREBP is cleaved by S1P and S2P (site-1 protease and site-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 sterol regulatory element (SRE), which stimulates the transcription of many genes. Among these are the low-density lipoprotein (LDL) receptor and HMG-CoA reductase. The LDL receptor scavenges circulating LDL from the bloodstream, whereas

title: Cholesterol 7 alpha-hydroxylase

text: hydroxylase reducing and oxidizing that molecule. Deficiency of this enzyme will increase the possibility of cholesterol gallstones. Disruption of CYP7A1 from classic bile acid synthesis in mice leads to either increased postnatal death or a milder phenotype with elevated serum cholesterol. The latter is similar to the case in humans, where CYP7A1 mutations associate with high plasma low-density lipoprotein and hepatic cholesterol content, as well as deficient bile acid excretion. There is also a synergy between plasma low-density lipoprotein cholesterol (LDL-C) and risks of coronary artery disease (CAD). Glucose signaling also induces CYP7A1 gene transcription by epigenetic regulation of the

text: on HDL to cholesterol ester and allows the maturation of HDL. LCAT deficiency does not allow for HDL maturation resulting in its rapid catabolism of circulating apoA-1 and apoA-2. The remaining form of HDL resembles nascent HDL. The LCAT glycoprotein produces lysophosphatidylcholine and cholesterol ester and binds to lipoproteins after being secreted by the liver. Usually the enzyme produced is responsible for cholesterol ester formation and high density lipoprotein (HDL) metabolism, but in fish-eye disease the enzyme cannot esterify, or make the acid into an alkyl, cholesterol in HDL particles. However, there is only a partial deficiency because the enzyme

title: Cholesterol 25-hydroxylase

text: have been identified in macrophages from the testis. CH25H is an interferon-stimulated gene, and its primary product 25HC may have broad-spectrum antiviral activity, demonstrated in mice against HIV, ebola, Nipah virus, and Rift Valley Fever virus. Specifically, it blocks membrane fusion between the cell and virus, and may "implicate membrane-modifying oxysterols as potential antiviral therapeutics." Cholesterol 25-hydroxylase In enzymology, a cholesterol 25-hydroxylase () is an enzyme that catalyzes the chemical reaction The 3 substrates of this enzyme are cholesterol, an electron acceptor AH, and O, whereas its 3 products are 25-hydroxycholesterol (25HC), the reduction product A, and HO. This enzyme

title: Cholesterol-dependent cytolysin

text: change of pH in a medium from 7.4 to 6.0 caused a conformational change in perfringolysin O, leading to an alteration in the minimum cholesterol threshold required for binding. Another CDC, listeriolysin O (LLO), which functions at an acidic pH, will lose its function at a neutral pH at temperatures above 30 °C, which trigger the irreversible loss of activity by the unfolding of domain 3 in the soluble monomer. The presence of cholesterol in the membrane of the target cell is required for CDC pore formation. The arrangement of cholesterol molecules in the bilayer may also be important for

title: Cholesterol total synthesis

text: Cholesterol total synthesis Cholesterol total synthesis in chemistry describes the total synthesis of the complex biomolecule cholesterol and is considered a great scientific achievement. The research group of Robert Robinson with John Cornforth (Oxford University) published their synthesis in 1951 and that of Robert Burns Woodward with Franz Sondheimer (Harvard University) in 1952. Both groups competed for the first publication since 1950 with Robinson having started in 1932 and Woodward in 1949. According to historian Greg Mulheirn the Robinson effort was hampered by his micromanagement style of leadership and the Woodward effort was greatly facilitated by his good relationships with

title: Cholesterol 24-hydroxylase

text: first accomplished in 1999 and an extensive "Escherichia coli" expression and purification system was later developed in 2003. The enzymatic structure of the human cholesterol-24 hydroxylase was determined via crystallography at the Stanford Synchrotron Radiation Lightsource, and was shown to be a 57kDa (500 residues) monomeric heme-containing protein bound to the endoplasmic reticulum in neurons. Cholesterol-24 hydroxylase is similar in structure to many other cytochrome P450s, possessing, for example, the conserved stretch of 23 hydrophobic residues in the N-terminus that make up a transmembrane-anchoring domain (residues 3-27). Even so, the cholesterol-24 hydroxylase C-terminus has a unique proline-rich region of 5

title: Cholesterol side-chain cleavage enzyme

text: always active, however its activity is limited by the supply of cholesterol in the inner membrane. The supplying of cholesterol to this membrane (from the outer mitochondrial membrane) is, thus, considered the true rate-limiting step in steroid production. This step is mediated primarily by the steroidogenic acute regulatory protein (StAR or STARD1). Upon stimulation of a cell to make steroid, the amount of StAR available to transfer cholesterol to the inner membrane limits how fast the reaction can go (the acute phase). With prolonged (chronic) stimulation, it is thought that cholesterol supply becomes no longer an issue and that the

title: Cholesterol 7 alpha-hydroxylase

text: CYP7A1 transcription through the 5′-upstream region of the promoter. The average life of this enzyme is between two and three hours. Activity can be regulated by phosphorylation-dephosphorylation. CYP7A1 is upregulated by the nuclear receptor LXR (liver X receptor) when cholesterol (to be specific, oxysterol) levels are high. The effect of this upregulation is to increase the production of bile acids and reduce the level of cholesterol in hepatocytes. It is downregulated by Sterol regulatory element-binding proteins (SREBP) when plasma cholesterol levels are low. Bile acids provide feedback inhibition of CYP7A1 by at least two different pathways, both involving the farnesoid

title: The 8-Week Cholesterol Cure

text: The 8-Week Cholesterol Cure The New 8-Week Cholesterol Cure is a 1987 health book by Robert Kowalski, who wrote it as a personal recollection about dealing with cholesterol issues. Kowalski wrote the book after having two coronary bypass surgeries and a heart attack. He created the program detailed in the book after he realized that a diet change alone would not help him, and the book is sometimes credited with popularizing oat bran as a health food. Kowalski published three other books in the "8-Week Cholesterol Cure" series as well as "The Blood Pressure Cure: 8 Weeks to Lower Blood

title: National Cholesterol Education Program

text: National Cholesterol Education Program The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. Its goal is to reduce increased cardiovascular disease rates due to hypercholesterolemia (elevated cholesterol levels) in the United States of America. The program has been running since 1985. The assigned goal of the NCEP committee is to meet on a recurring basis, review ongoing scientific research about atherosclerotic cardiovascular disease and make simplified, consensus, committee recommendations to be promoted by the NIH, the American Heart Association and other groups to both