Cholesterol is a waxy steroid metabolite found in the cell membranes and transported in the blood plasma of all animals. It is an essential structural component of mammalian cell membranes, where it is required to establish proper membrane permeability and fluidity. In addition, cholesterol is an important component for the manufacture of bile acids, steroid hormones, and several fat-soluble vitamins. Cholesterol is the principal sterol synthesized by animals, but small quantities are synthesized in other eukaryotes, such as plants and fungi. It is almost completely absent among prokaryotes, which include bacteria.
Cholesterol is most popularly known to be a value given by doctors to their patients after a blood test that represents the quantity of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in their bloodstream. Fasting vs. non-fasting tests will give more specific results. A high level of LDL ("bad cholesterol") is considered to be undesirable, particularly for patients with a personal or familial history of coronary heart disease (CHD) because the smaller molecules are more easily able to penetrate the linings of blood vessels and cause arterial plaques or adversely affect the heart itself. Conversely, higher levels of HDL ("good cholesterol") are considered to be more desirable because this type appears to transport cholesterol out of the arteries to the liver where it can be reused or excreted from the body. Levels of both HDL and LDL can be influenced by one's diet (eating less meat products and increasing soluble fiber intake, like oatmeal, for example) as well as exercise. However, some people have a genetic predisposition to certain cholesterol levels and may need assistance in regulating them by using medications. People with a history of heart disease are encouraged to work on reducing LDL and increasing HDL more stringently than the average person in order to avoid future health problems.
The name cholesterol originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol, as François Poulletier de la Salle first identified cholesterol in solid form in gallstones, in 1769. However, it was only in 1815 that chemist Eugène Chevreul named the compound "cholesterine".
Physiology
Overview
Since cholesterol is essential for all animal life, it is primarily synthesized from simpler substances within the body. However, high levels in blood circulation, depending on how it is transported within lipoproteins, are strongly associated with progression of atherosclerosis. For a person of about 68 kg (150 pounds), typical total body cholesterol synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g. Typical daily additional dietary intake, in the United States and societies with similar dietary patterns, is 200–300 mg. The body compensates for cholesterol intake by reducing the amount synthesized.
Cholesterol is recycled. It is excreted by the liver via the bile into the digestive tract. Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream. Intestinal tract absorption is highly selective for cholesterol, excreting plant stanols and sterols (which promote atherosclerosis progression more than cholesterol), back into the intestinal lumen for elimination.
Function
Cholesterol is required to build and maintain membranes; it regulates membrane fluidity over the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups 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. In this structural role, cholesterol reduces the permeability of the plasma membrane to protons (positive hydrogen ions) and 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 such endocytosis can be investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol has also been implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane. In many neurons, 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.
Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, 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, Vitamin A, Vitamin D, Vitamin E, and Vitamin K. Cholesterol is an important precursor molecule for the synthesis of Vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives.
Some research indicates that cholesterol may act as an antioxidant.
Dietary sources
Animal fats are complex mixtures of triglycerides, with lesser amounts of phospholipids and cholesterol. As a consequence, all foods containing animal fat contain cholesterol to varying extents. Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, poultry, and shrimp. Human breast milk also contains significant quantities of cholesterol. Cholesterol is not present in plant-based food sources unless it has been added during the food's preparation. However, plant products such as flax seeds and peanuts contain cholesterol-like compounds called phytosterols, which are suggested to help lower serum cholesterol levels.
Total fat intake, especially saturated fat and trans fat, plays a larger role in blood cholesterol than intake of cholesterol itself. Saturated fat is present in full fat dairy products, animal fats, several types of oil and chocolate. Trans fats are typically derived from the partial hydrogenation of unsaturated fats, and, in contrast to other types of fat, do not occur in significant amounts in nature. Research supports a recommendation to minimize or eliminate trans fats from the diet due to their adverse health effects. Trans fat is most often encountered in margarine and hydrogenated vegetable fat, and consequently in many fast foods, snack foods, and fried or baked goods.
A change in diet in addition to other lifestyle modifications may help reduce blood cholesterol. Avoiding animal products may decrease the cholesterol levels in the body not through dietary cholesterol reduction alone but primarily through a reduced saturated fat intake. Those wishing to reduce their cholesterol through a change in diet should aim to consume less than 7% of their daily calories from saturated fat and less than 200 mg of cholesterol per day.
The view that a change in diet (to be specific, a reduction in dietary fat and cholesterol) can lower blood cholesterol levels, and thus reduce the likelihood of development of, among others, coronary artery disease (CHD) has been challenged. An alternative view is that any reductions to dietary cholesterol intake are counteracted by the organs such as the liver, which will increase or decrease production of cholesterol to keep blood cholesterol levels constant.
Synthesis
About 20–25% of total daily cholesterol production occurs in the liver; other sites of high synthesis rates include the intestines, adrenal glands, and reproductive organs. Synthesis within the body starts with one molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are dehydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This step is an irreversible step in cholesterol synthesis and is the site of action for the statins (HMG-CoA Reductase Inhibitors).
Mevalonate is then converted to 3-isopentenyl pyrophosphate in three reactions that require ATP. This molecule is decarboxylated to isopentenyl pyrophosphate, which is a key metabolite for various biological reactions. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate 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 then converted to cholesterol.
Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine in 1964 for their discoveries concerning the mechanism and regulation of cholesterol and fatty acid metabolism.
Regulation of cholesterol synthesis
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 choles
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