Cholesterol 7-alpha-Hydroxylase: A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS.Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.25-Hydroxyvitamin D3 1-alpha-Hydroxylase: A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol).Milk Substitutes: Food BEVERAGES that are used as nutritional substitutes for MILK.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion.Cholestanetriol 26-Monooxygenase: An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.Cholic Acids: The 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholanic acid family of bile acids in man, usually conjugated with glycine or taurine. They act as detergents to solubilize fats for intestinal absorption, are reabsorbed by the small intestine, and are used as cholagogues and choleretics.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Cholesterol, Dietary: Cholesterol present in food, especially in animal products.Cholestyramine Resin: A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium Cl(-) anion.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines (INTESTINAL REABSORPTION) into portal circulation, passage back into liver, and re-excretion in bile.Steroid 12-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.Cholesterol, LDL: Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol.Taurocholic Acid: The product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic.Cholesterol, HDL: Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.Phenylalanine Hydroxylase: An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC 1.14.16.1.Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.Hydroxycholesterols: Cholesterol which is substituted by a hydroxy group in any position.Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.Cholestenones: CHOLESTENES with one or more double bonds and substituted by any number of keto groups.Steroid 21-Hydroxylase: An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Sterols: Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)Bile Ducts: The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Gallbladder: A storage reservoir for BILE secretion. Gallbladder allows the delivery of bile acids at a high concentration and in a controlled manner, via the CYSTIC DUCT to the DUODENUM, for degradation of dietary lipid.Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Organic Anion Transporters, Sodium-Dependent: A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is driven either directly or indirectly by a gradient of sodium ions.Kinetics: The rate dynamics in chemical or physical systems.Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of TRYPTOPHAN to 5-HYDROXYTRYPTOPHAN in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of SEROTONIN.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Cholesterol Oxidase: An enzyme that catalyzes the oxidation of cholesterol in the presence of molecular oxygen to 4-cholesten-3-one and hydrogen peroxide. The enzyme is not specific for cholesterol, but will also oxidize other 3-hydroxysteroids. EC 1.1.3.6.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.Cholelithiasis: Presence or formation of GALLSTONES in the BILIARY TRACT, usually in the gallbladder (CHOLECYSTOLITHIASIS) or the common bile duct (CHOLEDOCHOLITHIASIS).Mevalonic AcidTriglyceridesFeces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Sitosterols: A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Hypercholesterolemia: A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Lipoproteins: Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.Anticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Biliary Fistula: Abnormal passage in any organ of the biliary tract or between biliary organs and other organs.Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Cholenes: Unsaturated derivatives of cholane with methyl groups at C-10 and C-13 and a branched five-carbon chain at C-17. They must have at least one double bond in the ring system.Xanthomatosis, Cerebrotendinous: An autosomal recessive lipid storage disorder due to mutation of the gene CYP27A1 encoding a CHOLESTANETRIOL 26-MONOOXYGENASE. It is characterized by large deposits of CHOLESTEROL and CHOLESTANOL in various tissues resulting in xanthomatous swelling of tendons, early CATARACT, and progressive neurological symptoms.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Xanthomatosis: A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Procollagen-Proline Dioxygenase: A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Dehydrocholesterols: Cholesterol derivatives having an additional double bond in any position. 24-Dehydrocholesterol is DESMOSTEROL. The other most prevalent dehydrocholesterol is the 7-isomer. This compound is a precursor of cholesterol and of vitamin D3.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Cholates: Salts and esters of CHOLIC ACID.Cholestanols: Cholestanes substituted in any position with one or more hydroxy groups. They are found in feces and bile. In contrast to bile acids and salts, they are not reabsorbed.Glycocholic Acid: The glycine conjugate of CHOLIC ACID. It acts as a detergent to solubilize fats for absorption and is itself absorbed.TritiumMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Lipoproteins, HDL: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.Psyllium: Dried, ripe seeds of PLANTAGO PSYLLIUM; PLANTAGO INDICA; and PLANTAGO OVATA. Plantain seeds swell in water and are used as demulcents and bulk laxatives.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Chromatography, Gas: Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.Cholesterol, VLDL: Cholesterol which is contained in or bound to very low density lipoproteins (VLDL). High circulating levels of VLDL cholesterol are found in HYPERLIPOPROTEINEMIA TYPE IIB. The cholesterol on the VLDL is eventually delivered by LOW-DENSITY LIPOPROTEINS to the tissues after the catabolism of VLDL to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LDL.trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride: An anticholesteremic agent that inhibits sterol biosynthesis in animals.Cholestenes: Steroids with methyl groups at C-10 and C-13 and a branched 8-carbon chain at C-17. Members include compounds with any degree of unsaturation; however, CHOLESTADIENES is available for derivatives containing two double bonds.Taurochenodeoxycholic Acid: A bile salt formed in the liver by conjugation of chenodeoxycholate with taurine, usually as the sodium salt. It acts as detergent to solubilize fats in the small intestine and is itself absorbed. It is used as a cholagogue and choleretic.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Bile Canaliculi: Minute intercellular channels that occur between liver cells and carry bile towards interlobar bile ducts. Also called bile capillaries.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Organic Chemistry Phenomena: The conformation, properties, reaction processes, and the properties of the reactions of carbon compounds.Receptor, Fibroblast Growth Factor, Type 4: A fibroblast growth factor receptor that is mainly expressed in LUNG; KIDNEY; PANCREAS; and SPLEEN. It also plays an important role in SKELETAL MUSCLE development and can contribute to NEOPLASTIC CELL TRANSFORMATION.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.Mesocricetus: A genus of the family Muridae having three species. The present domesticated strains were developed from individuals brought from Syria. They are widely used in biomedical research.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Taurodeoxycholic Acid: A bile salt formed in the liver by conjugation of deoxycholate with taurine, usually as the sodium salt. It is used as a cholagogue and choleretic, also industrially as a fat emulsifier.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Common Bile Duct: The largest bile duct. It is formed by the junction of the CYSTIC DUCT and the COMMON HEPATIC DUCT.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Orphan Nuclear Receptors: A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Sterol O-Acyltransferase: An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26.Lipoproteins, LDL: A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.Naphazoline: An adrenergic vasoconstrictor agent used as a decongestant.Feedback: A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Cholestanes: Derivatives of the saturated steroid cholestane with methyl groups at C-18 and C-19 and an iso-octyl side chain at C-17.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.Mice, Inbred C57BLAcetates: Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.Clofibric Acid: An antilipemic agent that is the biologically active metabolite of CLOFIBRATE.Fatty Acid Synthases: Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Hepatocyte Nuclear Factor 4: A subfamily of nuclear receptors that regulate GENETIC TRANSCRIPTION of a diverse group of GENES involved in the synthesis of BLOOD COAGULATION FACTORS; and in GLUCOSE; CHOLESTEROL; and FATTY ACIDS metabolism.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cystic Duct: The duct that is connected to the GALLBLADDER and allows the emptying of bile into the COMMON BILE DUCT.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Hyperlipoproteinemia Type II: A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins).Cholecystectomy: Surgical removal of the GALLBLADDER.Acyl Coenzyme A: S-Acyl coenzyme A. Fatty acid coenzyme A derivatives that are involved in the biosynthesis and oxidation of fatty acids as well as in ceramide formation.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Hydroxysteroid Dehydrogenases: Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Diet: Regular course of eating and drinking adopted by a person or animal.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Racemases and Epimerases: Enzymes that catalyze inversion of the configuration around an asymmetric carbon in a substrate having one (racemase) or more (epimerase) center(s) of asymmetry. (Dorland, 28th ed) EC 5.1.Acetyl-CoA Carboxylase: A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.Benzopyrene Hydroxylase: A drug-metabolizing, cytochrome P-448 (P-450) enzyme which catalyzes the hydroxylation of benzopyrene to 3-hydroxybenzopyrene in the presence of reduced flavoprotein and molecular oxygen. Also acts on certain anthracene derivatives. An aspect of EC 1.14.14.1.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Cholagogues and Choleretics: Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).Apolipoprotein A-I: The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.Adrenal Hyperplasia, Congenital: A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.Peroxisomal Bifunctional Enzyme: A monomeric protein found in liver peroxisomes that contains two enzymatically active domains; an enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase domain, and an (S)-3-hydroxyacyl-CoA dehydrogenase domain. The enzyme is stereospecific with regards to how cis and trans double bonds are metabolized. It is complemented by PEROXISOMAL MULTIFUNCTIONAL PROTEIN-2, which has the opposite stereospecificity.Bile Pigments: Linear TETRAPYRROLES that give a characteristic color to BILE including: BILIRUBIN; BILIVERDIN; and bilicyanin.Cerulenin: An epoxydodecadienamide isolated from several species, including ACREMONIUM, Acrocylindrum, and Helicoceras. It inhibits the biosynthesis of several lipids by interfering with enzyme function.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Enoyl-CoA Hydratase: An enzyme that catalyzes reversibly the hydration of unsaturated fatty acyl-CoA to yield beta-hydroxyacyl-CoA. It plays a role in the oxidation of fatty acids and in mitochondrial fatty acid synthesis, has broad specificity, and is most active with crotonyl-CoA. EC 4.2.1.17.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).4-Hydroxybenzoate-3-Monooxygenase: A flavoprotein that catalyzes the synthesis of protocatechuic acid from 4-hydroxybenzoate in the presence of molecular oxygen. EC 1.14.13.2.Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.beta-Cyclodextrins: Cyclic GLUCANS consisting of seven (7) glucopyranose units linked by 1,4-glycosidic bonds.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Biliary Tract: The BILE DUCTS and the GALLBLADDER.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Taurine: A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids.Bile Duct Diseases: Diseases in any part of the ductal system of the BILIARY TRACT from the smallest BILE CANALICULI to the largest COMMON BILE DUCT.Phytosterols: A class of organic compounds known as STEROLS or STEROIDS derived from plants.Bile Ducts, Intrahepatic: Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Symporters: Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Bile Reflux: Retrograde bile flow. Reflux of bile can be from the duodenum to the stomach (DUODENOGASTRIC REFLUX); to the esophagus (GASTROESOPHAGEAL REFLUX); or to the PANCREAS.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.ATP Binding Cassette Transporter 1: A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cyclodextrins: A homologous group of cyclic GLUCANS consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances.Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes.Hyperlipidemias: Conditions with excess LIPIDS in the blood.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.3-Hydroxyacyl CoA Dehydrogenases: Enzymes that reversibly catalyze the oxidation of a 3-hydroxyacyl CoA to 3-ketoacyl CoA in the presence of NAD. They are key enzymes in the oxidation of fatty acids and in mitochondrial fatty acid synthesis.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Bile Duct Neoplasms: Tumors or cancer of the BILE DUCTS.Bacterial Proteins: Proteins found in any species of bacterium.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.Liver Diseases: Pathological processes of the LIVER.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Chemical Phenomena: The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.UridineCycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Diterpenes: Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.ThymidineElectrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Glycochenodeoxycholic Acid: A bile salt formed in the liver from chenodeoxycholate and glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is a cholagogue and choleretic.Apolipoproteins B: Major structural proteins of triacylglycerol-rich LIPOPROTEINS. There are two forms, apolipoprotein B-100 and apolipoprotein B-48, both derived from a single gene. ApoB-100 expressed in the liver is found in low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). ApoB-48 expressed in the intestine is found in CHYLOMICRONS. They are important in the biosynthesis, transport, and metabolism of triacylglycerol-rich lipoproteins. Plasma Apo-B levels are high in atherosclerotic patients but non-detectable in ABETALIPOPROTEINEMIA.Desmosterol: An intermediate in the synthesis of cholesterol.
... the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, ... "Correlation of farnesoid X receptor coactivator recruitment and cholesterol 7alpha-hydroxylase gene repression by bile acids". ... "Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the ... In this way, a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are ...
Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. The body produces about ... An alternative (acidic) pathway of bile acid synthesis is initiated by mitochondrial sterol 27-hydroxylase (CYP27A1), expressed ... termed alpha (α; displayed as a dashed line). All bile acids have a 3-hydroxyl group, derived from the parent molecule, ... Bile acid synthesis occurs in liver cells which synthesize primary bile acids (cholic acid and chenodeoxycholic acid in humans ...
... and is important for the synthesis of bile acid and the regulation of cholesterol levels. Cholesterol 7 alpha-hydroxylase is ... the first and rate limiting step in bile acid synthesis. The inhibition of cholesterol 7-alpha-hydroxylase (CYP7A1) represses ... Glucose induction of bile acid synthesis have an important implication in metabolic control of glucose, lipid, and energy ... the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7α ...
... which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be ... "Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe ... biologic role in the regulation of cholesterol synthesis". J. Lipid Res. 38 (5): 1053-8. PMID 9186922. Li-Hawkins J, Lund EG, ... Wu Z, Martin KO, Javitt NB, Chiang JY (2000). "Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene ...
... both of which are secreted in the bile. In the intestine these bile acids affect the solubility of cholesterol and other lipids ... CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) also known as sterol 12-alpha-hydroxylase is a protein which in ... Ellis EC (2006). "Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes". World J. Gastroenterol. ... The balance between these two steroids determines the relative amounts of the two primary bile acids, cholic acid and ...
"Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis". Gastroenterology ... reflects the loss of bile acids secondary to bile acid malabsorption or the increased synthesis found in primary bile acid ... Hofmann, AF; Mangelsdorf, DJ; Kliewer, SA (2009). "Chronic diarrhea due to excessive bile acid synthesis and not defective ... Russell, DW (2003). "The enzymes, regulation, and genetics of bile acid synthesis". Annual Review of Biochemistry. 72: 137-74. ...
... is metabolized to protocatechuic acid (PCA) and phloroglucinol carboxylic acid (PGCA). It is also degraded by ... hydroxylase and further oxidized to taxifolin by flavanone 3-hydroxylase. Taxifolin is then reduced by dihydroflavanol 4- ... Bogs J, Downey MO, Harvey JS, Ashton AR, Tanner GJ, Robinson SP (October 2005). "Proanthocyanidin synthesis and expression of ... Epigeoside (Catechin-3-O-alpha-L-rhamnopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside) can be isolated from ...
The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol. Cholesterol can, in turn, be used ... To turn them into amino acids the alpha keto-acids formed from the citric acid cycle intermediates have to acquire their amino ... hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF". J. Biol. ... to synthesize the steroid hormones, bile salts, and vitamin D. The carbon skeletons of many non-essential amino acids are made ...
"Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha". Cell. 93 (5): 693- ... LXRs regulate fatty acid synthesis by modulating the expression of sterol regulatory element binding protein-1c (SREBP-1c). ... Song C, Liao S (November 2000). "Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha". Endocrinology. ... Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier ...
Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one after intravenous administration to bile duct-cannulated rats". J. Biol ... Other early-stage cholesterol synthesis inhibitors like colestolone. 7-Dehydrocholesterol reductase (7-DHCR) inhibitors such as ... and trilostane was formerly used to inhibit corticosteroid synthesis in the treatment of Cushing's syndrome. 17α-Hydroxylase/17 ... HMG-CoA reductase (HMGCR) inhibitors, also known as statins, prevent the conversion of HMG-CoA into mevalonic acid, a ...
CYP27A1 (bile acid biosynthesis), CYP27B1 (vitamin D3 1-alpha hydroxylase, activates vitamin D3), CYP27C1 (unknown function) ... including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 ... cholesterol 24-hydroxylase. 1 subfamily, 1 gene. CYP46A1 CYP51. cholesterol biosynthesis. 1 subfamily, 1 gene, 3 pseudogenes. ... retinoic acid hydroxylase. 3 subfamilies, 3 genes. CYP26A1, CYP26B1, CYP26C1 CYP27. varied. 3 subfamilies, 3 genes. ...
Rosenheim O, King H (1932). "The Ring-system of sterols and bile acids. Part II". J. Chem. Technol. Biotechnol. 51 (47): 954-7 ... vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells, and affects the synthesis of ... The conversion of calcifediol to calcitriol is catalyzed by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, which is the ... The major natural source of the vitamin is synthesis of cholecalciferol in the skin from cholesterol through a chemical ...
... by the synthesis of androstenedione from cholesterol. Androstenedione is a substance of weak androgenic activity which serves ... Resorcylic acid lactones (e.g., zearalanone, α-zearalenol, β-zearalenol, zearalenone, zeranol (α-zearalanol), taleranol ( ... In contrast, granulosa cells lack 17α-hydroxylase and 17,20-lyase, whereas theca cells express these enzymes and 17β-HSD but ... "DHEA metabolites activate estrogen receptors alpha and beta". Steroids. 78 (1): 15-25. doi:10.1016/j.steroids.2012.10.002. PMC ...
The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol. Cholesterol can, in turn, be used ... To turn them into amino acids the alpha keto-acids formed from the citric acid cycle intermediates have to acquire their amino ... hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF". J. Biol. ... to synthesize the steroid hormones, bile salts, and vitamin D.[35][36] ...
... genetic removal of Cyp7a1 promotes increased intestinal sterol synthesis and increases 12-alpha-hydroxylase (Cyp8b1) expression ... Alternate pathways of bile acid synthesis in the cholesterol 7alpha-hydroxylase knockout mouse are not upregulated by either ... Fuchs M. Bile acid regulation of hepatic physiology. III. Regulation of bile acid synthesis: past progress and future ... including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to ...
... cholesterol into bile acids was measured. Bile acid synthesis was stimulated in a dose-dependent way by glucocorticoids, but ... As with bile acid synthesis from [14C]cholesterol, no change in enzyme activity was found in hepatocytes cultured in the ... an intermediate of the bile acid pathway, to bile acids was not affected by dexamethasone. Measurement of cholesterol 7 alpha- ... Dexamethasone regulates bile acid synthesis in monolayer cultures of rat hepatocytes by induction of cholesterol 7α-hydroxylase ...
Insulin suppresses bile acid synthesis in cultured rat hepatocytes by down-regulation of cholesterol 7 alpha-hydroxylase and ... Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of hepatocyte nuclear factor 4alpha in ... Bile acids promote bile formation and facilitate dietary lipid absorption. Animal and human studies showing disturbed bile acid ... Bile acids are activating ligands of the farnesoid X receptor (FXR), a nuclear receptor with an established role in bile acid ...
... knockout mice develops spontaneous hypercholesterolemia but the detailed mechanisms by which EP4 affects cholesterol ... EP4 plays a critical role in maintaining cholesterol homeostasis by regulating the synthesis and elimination of bile acids. ... Deficiency of EP4 significantly decreased total bile acid levels in the liver by 26.2% and the fecal bile acid content by 27.6 ... Activation of EP4 serves as an effective novel strategy to promote cholesterol disposal in the forms of bile acids in order to ...
... and is important for the synthesis of bile acid and the regulation of cholesterol levels. Cholesterol 7 alpha-hydroxylase is ... the first and rate limiting step in bile acid synthesis. The inhibition of cholesterol 7-alpha-hydroxylase (CYP7A1) represses ... Glucose induction of bile acid synthesis have an important implication in metabolic control of glucose, lipid, and energy ... the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7α ...
Ketoconazole blocks bile acid synthesis in hepatocyte monolayer cultures and in vivo in rat by inhibiting cholesterol 7 alpha- ... The liver transaminates amino acids to corresponding α-keto acid gluconeogenic substrates. Alpha-ketoglutarate is often the α- ... hydroxylase. J Clin Invest. 1986;78:1064-1071. [PMC free article] [PubMed] ... For example, fatty acids act as ligands for several of the PPAR nuclear hormone receptors, bile acids activate FXR in liver, ...
hydroxylase, (C7.alpha.OH), being the rate limiting steps in the synthesis of cholesterol and bile acids, respectively. Animals ... hydroxylase (C7.alpha.OH), the key regulatory step in the synthesis of bile acids. (Ishibashi, S. et al. 1993. J. Clin. Invest ... Kurt Einarsson et al, "Bile Acid Synthesis in Man: Assay of Hepatic Microsomal Cholesterol 7.alpha.-Hydroxylase Activity by ... hydroxylase (C7.alpha.OH), a key regulatory step inbile acid synthesis. According to the present invention it is shown that GH ...
This has been suggested because the enzyme needed for the first step in bile acid synthesis, cholesterol 7-alpha hydroxylase, ... Bile acid formation, and hence cholesterol degradation are highly dependent on AA. Some hypothesize that vitamin C may even ... Ascorbic acid (AA) is an odorless, white solid having the chemical formula C6H8O6. The vitamin is easily oxidized to form ... The term ascorbic acid was adopted to describe its ability to prevent scurvy. The vitamin was then synthesized in the ...
... the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, ... "Correlation of farnesoid X receptor coactivator recruitment and cholesterol 7alpha-hydroxylase gene repression by bile acids". ... "Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the ... In this way, a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are ...
... faecal excretion of cholesterol and bile acid, and hepatic concentrations of bile acids, cholesterol and cholesterol 7 alpha- ... which was probably caused by lower endogenous cholesterol synthesis, and higher n-3 PUFA in serum and tissues in obese Zucker ... hydroxylase mRNA when compared to Control Diet. Rats fed Baked Cod Diet had higher concentrations of n-3 PUFAs in serum, liver ... and lower hepatic mRNA concentrations of HMG-CoA reductase and sterol O-acyltransferase-2 without affecting serum bile acid ...
Disruption of the sterol 12alpha-hydroxylase gene (Cyp8b1) in mice prevents the synthesis … ... Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback ... Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback ... Steroid 12-alpha-Hydroxylase / deficiency * Steroid 12-alpha-Hydroxylase / genetics * Transcription Factors / metabolism ...
Cafestol, the cholesterol-raising factor in boiled coffee, suppresses bile acid synthesis by downregulation of cholesterol 7 ... alpha-hydroxylase and sterol 27-hydroxylase in rat hepatocytes. Post, S.M., de Wit, E.C., Princen, H.M. Arterioscler. Thromb. ... Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature ... The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human ...
... cholesterol as precursor for bile acid synthesis. Therefore, treatment of patients with this drug may inhibit bile acid ... Translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes.. ... Ketoconazole blocks bile acid synthesis in hepatocyte monolayer cultures and in vivo in rat by inhibiting cholesterol 7 alpha- ... hydroxylase.. H M Princen, … , R J Vonk, H J Kempen H M Princen, … , R J Vonk, H J Kempen ...
... involving in fatty acid synthesis, LDLR-mediated cholesterol uptake, bile acid biosynthesis and cholesterol efflux. This study ... LDLR-mediated cholesterol uptake, bile acid biosynthesis and cholesterol efflux. Experimental results indicated that DHG ... low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum ... regulating 3 lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and ...
Synthesis of Cholesterol, Bile Salts, and Acids flashcards from Annette Liem ... bile acids) and 50% unprotonated (bile salts). -OH groups are below plane of sterol ring (alpha); methyl groups are above (beta ... Unit 6 - Cholesterol Metabolism I; Synthesis of Cholesterol, Bile Salts, and Acids Flashcards Preview Molecular and Cellular ... Flashcards in Unit 6 - Cholesterol Metabolism I; Synthesis of Cholesterol, Bile Salts, and Acids Deck (26): ...
... the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 ... Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), ...
Bile acid composition is an indicator of the homeostasis and turnover of cholesterol as well as of bile acid metabolism ... α-hydroxylase. d4-CA. cholic-2,2,4,4-d4 acid. d4-GCA. glycocholic-2,2,4,4-D4 acid. d4-TCA. tauro-cholic-2,2,4,4-D4 acid. DCA. ... 2012) Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. ... 2009) The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in non alcoholic fatty ...
Gustafsson J; Bile acid synthesis during development. Mitochondrial 12 alpha-hydroxylation in human fetal liver.; J Clin ... Lund EG, Kerr TA, Sakai J, Li WP, Russell DW; cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane ... Cuebas DA, Phillips C, Schmitz W, Conzelmann E, Novikov DK; The role of alpha-methylacyl-CoA racemase in bile acid synthesis ... Dehydroascorbic acid. 102. GPX 2. SelP. 39. Trx-S2. 102, 159, 264. Ascorbic acid. 85. Lipoic acid. 264. PRDX4. GPX 1. NADP+. ...
Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. ... liver X receptor alpha (LXRA), and peroxisome proliferation activated receptor-α (PPARα), which facilitates the conversion of ... Kiyoshiebihara A, Schneeman O. Interaction of bile acids, phospholipids, cholesterol and triglyceride with dietary fibers in ... Cod protein powder lowered serum nonesterified fatty acids and increased total bile acid concentrations in healthy, lean, ...
... the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, ... In this way a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are ... Chenodeoxycholic acid and other bile acids are natural ligands for FXR.. Like other steroid receptors, when activated, FXR ... Posted in New Publications , Tagged bile acids, farnesoid X receptor, FXR, microbial fermentation, RORγt, T cells , Comments ...
... which catalyzes the rate-limiting step in bile acid synthesis (23). The resultant elevation in liver cholesterol content leads ... the relatively efficient absorption of dietary cholesterol and limited hepatic conversion of cholesterol to bile acids (18-20 ... The consequence is an inhibition in the conversion of cholesterol to bile acids by the liver due to dramatically decreased ... 22)). In response to a casein-supplemented diet, there is a greater reabsorption of bile acids by the small intestine into ...
Genomes and Genes about Experts and Doctors on steroid hydroxylases in Dallas, Texas, United States ... Schwarz M, Russell D, Dietschy J, Turley S. Alternate pathways of bile acid synthesis in the cholesterol 7alpha-hydroxylase ... steroid 17 alpha hydroxylase*25 hydroxyvitamin d3 1 alpha hydroxylase*cytochrome p450 family 7*dietary cholesterol* ... pathway of bile acid synthesis involving an inducible oxysterol 7alpha-hydroxylase plays a crucial role in lipid and bile acid ...
... we identified three loci affecting HDL-cholesterol levels in a screen for ENU-induced mutations in mice and discovered two ... The cholesterol and bile acid synthesis enzyme cholesterol 7 alpha-hydroxylase (Cyp7a1) mRNA was increased by 55% in Ampd2m/m ... This may be a compensatory mechanism to enhance cholesterol disposal through bile acid synthesis and secretion and switching to ... Han S, Vaziri ND, Gollapudi P, Kwok V, Moradi H: Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome. Am J ...
Omega 3 fatty acids - omega-3s exhibit cardioprotective effects, fish oil part of regimen to protect against heart disease ... Further, alpha-linolenic acid produced strong plasma cholesterol-lowering effects and higher TBARS concentrations. ... Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected ... Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol ...
Clayton PT; Disorders of bile acid synthesis.; J Inherit Metab Dis, 2011 PubMed Europe PMC*Noshiro M, Okuda K; Molecular ... LXR-alpha. Cyp7B1. 24S-diHC. Cholesterol. Estrogen receptor alpha. EBI2. DDA. 27. 22. 5,6-alpha-Epoxycholesterol. Cholestane-3- ... AKA cholesterol 25-hydroxylase. ChEH. Protein. P34913 (Uniprot-TrEMBL) *AKA cholesterol epoxide hydrolase (ChEH); EC: 3.3.2.11* ... Russell DW; The enzymes, regulation, and genetics of bile acid synthesis.; Annu Rev Biochem, 2003 PubMed Europe PMC*Norlin ...
  • DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. (frontiersin.org)
  • A key player in reverse cholesterol transport is the high density lipoprotein (HDL). (biomedcentral.com)
  • Besides increasing LDL (low-density lipoprotein or "bad") cholesterol levels, trans fats also reduce the level of HDL (high-density lipoprotein or "good") cholesterol. (progressivehealth.com)
  • The RBBF and SBBF increased the levels of high density lipoprotein cholesterol (HDL-c). (springeropen.com)
  • 5 The metabolic syndrome has been defined by the National Cholesterol Education Program as a cluster of at least 3 of 5 criteria: insulin resistance and glucose intolerance, abdominal obesity, hypertension, low high-density lipoprotein (HDL) cholesterol, and hypertriglyceridemia. (ahajournals.org)
  • Previously, we identified three loci affecting HDL-cholesterol levels in a screen for ENU-induced mutations in mice and discovered two mutated genes. (biomedcentral.com)
  • Because aging increases significantly biliary cholesterol hypersecretion and gallstone prevalence in C57L mice carrying Lith genes, it is highly like that Longevity (aging) genes can enhance lithogenesis of Lith (gallstone) genes. (elsevier.com)
  • Previously oxysterols where though to be inactive metabolic intermediates, however recent findings have established that these metabolites are involved in cholesterol homoeostasis, can be ligands to nuclear and G protein-coupled receptors and biomarkers of diseases (for example Niemann-Pick disease). (wikipathways.org)
  • Within the gallbladder bile, biologic molecules influence the process in a positive or negative fashion. (medscape.com)
  • Arachidonyl lecithin, which is absorbed from the alimentary tract and secreted into the bile, stimulates prostanoid synthesis by gallbladder mucosa and promotes mucus hypersecretion, while inhibitors of prostaglandin inhibit mucus secretion. (medscape.com)
  • Finally, gallbladder hypomotility and bile stasis appear to promote gallstone formation and growth, which may be important in diabetes, pregnancy, oral contraceptive use in women, and prolonged fasting in critically ill patients on total parenteral nutrition. (medscape.com)
  • Accordingly, chow-fed P2Y 13 knockout (P2Y 13 -/- ) mice exhibit lower hepatic HDL uptake, which translates into a decrease of hepatic free cholesterol content and biliary cholesterol and phospholipid secretion. (biomedcentral.com)
  • We showed that P2Y 13 -deficient mice (P2Y 13 -/- ) exhibited a decrease in hepatic HDL uptake, hepatic cholesterol content, and biliary cholesterol output, although their plasma HDL-C and other lipid levels were normal. (biomedcentral.com)
  • PBC is a rare disease in which a chronic, immune-mediated injury to the small intrahepatic bile ducts leads to an imbalance between cholangiocyte proliferation and apoptosis, with resulting ductopaenia, fibrosis and eventually biliary cirrhosis. (medscape.com)
  • Primary sclerosing cholangitis affects predominantly medium- to large-sized bile ducts, with progressive inflammation and fibrosis leading to multifocal biliary strictures. (medscape.com)
  • Biliary disease is caused by abnormalities in bile composition, biliary anatomy, or function. (medscape.com)
  • Biliary-type pain, the typical clinical presentation, is due to the obstruction of the bile duct lumen. (medscape.com)