Bile Acids
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Bile Acids
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary bile acids are those synthesized by the liver. Secondary bile acids result from bacterial actions in the colon (anatomy), colon. In humans, taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile salts. The salts of their 7-alpha-dehydroxylated derivatives, deoxycholic acid and lithocholic acid, are also found, with derivatives of cholic, chenodeoxycholic and deoxycholic acids accounting for over 90% of human biliary bile acids. Description Bile acids comprise about 80% of the organic compounds in bile (others are phospholipids and cholesterol). An increased secretion of bile acids produces an ...
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Steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and as signal transduction, signaling molecules. Examples include the lipid cholesterol, sex hormones estradiol and testosterone, anabolic steroids, and the anti-inflammatory corticosteroid drug dexamethasone. Hundreds of steroids are found in Fungus, fungi, plants, and animals. All steroids are manufactured in cells from a sterols, sterol: Cholesterol, cholesterol (animals), lanosterol (opisthokonts), or cycloartenol (plants). All three of these molecules are produced via Cyclic compound, cyclization of the triterpene squalene. Structure The steroid nucleus (parent structure, core structure) is called gonane (cyclopentanoperhydrophenanthrene). It is typically composed of seventeen carbon atoms, bonded in fou ...
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Lithocholic Acid
Lithocholic acid, also known as 3α-hydroxy-5β-cholan-24-oic acid or LCA, is a bile acid that acts as a detergent to solubilize fats for absorption. Bacterial action in the colon produces LCA from chenodeoxycholic acid by reduction of the hydroxyl functional group at carbon-7 in the "B" ring of the steroid framework. It has been implicated in human and experimental animal carcinogenesis. Preliminary ''in vitro'' research suggests that LCA selectively kills neuroblastoma cells, while sparing normal neuronal cells and is cytotoxic to numerous other malignant cell types at physiologically relevant concentrations. Dietary fiber can bind to lithocholic acid and aid in its excretion in stool; as such, fiber can protect against colon cancer. LCA (and LCA acetate and LCA propionate) can activate the vitamin D receptor without raising calcium levels as much as vitamin D itself. LCA binds with 20 μM affinity to the human membrane enzyme NAPE-PLD, enhancing dimer assembly and enabling ...
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Rate-limiting Step
In chemical kinetics, the overall rate of a reaction is often approximately determined by the slowest step, known as the rate-determining step (RDS or RD-step or r/d step) or rate-limiting step. For a given reaction mechanism, the prediction of the corresponding rate equation (for comparison with the experimental rate law) is often simplified by using this approximation of the rate-determining step. In principle, the time evolution of the reactant and product concentrations can be determined from the set of simultaneous rate equations for the individual steps of the mechanism, one for each step. However, the analytical solution of these differential equations is not always easy, and in some cases numerical integration may even be required. The hypothesis of a single rate-determining step can greatly simplify the mathematics. In the simplest case the initial step is the slowest, and the overall rate is just the rate of the first step. Also, the rate equations for mechanisms with a ...
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Cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. In mammals, these enzymes oxidize steroids, fatty acids, xenobiotics, and participate in many biosyntheses. By hydroxylation, CYP450 enzymes convert xenobiotics into hydrophilic derivatives, which are more readily excreted. P450s are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived from the spectrophotometry, spectrophotometric peak at the wavelength of the absorption spectroscopy, absorption maximum of the enzyme (450 nanometre, nm) when it is in the redox, reduced state and complexed with carbon monoxide. Most P450s require a protein partner to deliver one or more electrons to reduc ...
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Hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bile salts and phospholipids * Detoxification, modification, and excretion of exogenous and endogenous substances * Initiation of formation and secretion of bile Structure The typical hepatocyte is cubical with sides of 20-30  μm, (in comparison, a human hair has a diameter of 17 to 180 μm).The diameter of human hair ranges from 17 to 181 μm. The typical volume of a hepatocyte is 3.4 x 10−9 cm3. Smooth endoplasmic reticulum is abundant in hepatocytes, in contrast to most other cell types. Microanatomy Hepatocytes display an eosinophilic cytoplasm, reflecting numerous mitochondria, and basophilic stippling due to large amounts of rough endoplasmic reticulum and free ribosomes. Brown lipofuscin granules are also observed (wit ...
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Cholic Acid Vs Other Bile Acids
Colic or cholic () is a form of pain that starts and stops abruptly. It occurs due to muscular contractions of a hollow tube (small and large intestine, gall bladder, ureter, etc.) in an attempt to relieve an obstruction by forcing content out. It may be accompanied by sweating and vomiting. Types include: *Baby colic, a condition, usually in infants, characterized by incessant crying *Biliary colic, blockage by a gallstone of the common bile duct or cystic duct *Devon colic or painter's colic, a condition caused by lead poisoning *Horse colic, a potentially fatal condition experienced by horses, caused by intestinal displacement or blockage *Renal colic, a pain in the flank, characteristic of kidney stone Kidney stone disease (known as nephrolithiasis, renal calculus disease, or urolithiasis) is a crystallopathy and occurs when there are too many minerals in the urine and not enough liquid or hydration. This imbalance causes tiny pieces of cr ...s The term is . Refer ...
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GPBAR1
The G protein-coupled bile acid receptor 1 (GPBAR1) also known as G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or Takeda G protein-coupled receptor 5 (TGR5) is a protein that in humans is encoded by the ''GPBAR1'' gene. Activated by bile acids, these receptors play a crucial role in metabolic regulation, including insulin secretion and energy balance, and are found in the gastrointestinal tract as well as other tissues throughout the body. History TGR5 receptors were first discovered by Takaharu Maruyama in 2002. It was the first membrane bound G protein coupled receptor that was discovered for faster bile acid signaling. Initially, up until the late 90's, bile acids were known only for its metabolic function of emulsifying fats and keeping cholesterol homeostasis. It wasn't until 1999 when researchers began exploring into its role as a hormone and signaling molecule with the discovery of the nuclear bile acid receptors, Farnesoid X Rece ...
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Farnesoid X Receptor
The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes. One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the ''CYP7A1'' promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the ''CYP7A1'' gene. FXR likewise stimula ...
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Fatty Acid Metabolism
Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds. In catabolism, fatty acids are metabolized to produce energy, mainly in the form of adenosine triphosphate (ATP). When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO2 and water by beta oxidation and the citric acid cycle. Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants. In anabolism, intact fatty acids are important precursors to triglycerides, phospholipids, second messengers, hormones and ketone bodies. For exa ...
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Chyme
Chyme or chymus (; ) is the semi-fluid mass of partly digested food that is expelled by the stomach, through the pyloric valve, into the duodenum (the beginning of the small intestine). Chyme results from the mechanical and chemical breakdown of a bolus and consists of partially digested food, water, hydrochloric acid, and various digestive enzymes. Chyme slowly passes through the pyloric sphincter and into the duodenum, where the extraction of nutrients begins. Depending on the quantity and contents of the meal, the stomach will digest the food into chyme in some time from 40 minutes to 3 hours. With a pH of approximately 2, chyme emerging from the stomach is very acidic. The duodenum secretes a hormone, cholecystokinin (CCK), which causes the gall bladder to contract, releasing alkaline bile into the duodenum. CCK also causes the release of digestive enzymes from the pancreas. The duodenum is a short section of the small intestine located between the stomach and the re ...
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Surfactant
Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. The word ''surfactant'' is a Blend word, blend of "surface-active agent", coined in 1950. As they consist of a water-repellent and a water-attracting part, they enable water and oil to mix; they can form foam and facilitate the detachment of dirt. Surfactants are among the most widespread and commercially important chemicals. Private households as well as many industries use them in large quantities as detergent, detergents and cleaning agents, but also for example as emulsion#Emulsifiers, emulsifiers, wetting agents, foaming agents, Antistatic agent, antistatic additives, or dispersants. Surfactants occur naturally in traditional plant-based detergents, e.g. Aesculus, horse chestnuts or Sapindus, soap nuts; they can also be found in the secretions of some caterpillars. Today one of the most commonly used anionic surfa ...
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Micelle
A micelle () or micella () ( or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension (also known as associated colloidal system). A typical micelle in water forms an aggregate, with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle centre. This phase is caused by the packing behavior of single-tail lipids in a bilayer. The difficulty in filling the volume of the interior of a bilayer, while accommodating the area per head group forced on the molecule by the hydration of the lipid head group, leads to the formation of the micelle. This type of micelle is known as a normal-phase micelle (or oil-in-water micelle). Inverse micelles have the head groups at the centre with the tails extending out (or water-in-oil micelle). Micelles are approximately spherical in shape. Other shapes, such ...
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