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).
Food BEVERAGES that are used as nutritional substitutes for MILK.
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.
The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Cholesterol present in food, especially in animal products.
Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.
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.
Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol.
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).
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.
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.
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.
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.
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.
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.
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
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.
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)
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.
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.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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.
Substances used to lower plasma CHOLESTEROL levels.
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.
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.
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)
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
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.
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.
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.
Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
The rate dynamics in chemical or physical systems.
A flavoprotein that catalyzes the synthesis of protocatechuic acid from 4-hydroxybenzoate in the presence of molecular oxygen. EC 1.14.13.2.
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.
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.
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.
Cholesterol which is substituted by a hydroxy group in any position.
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.
A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.
Cyclic GLUCANS consisting of seven (7) glucopyranose units linked by 1,4-glycosidic bonds.
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.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
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.
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.
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.
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.
A class of organic compounds known as STEROLS or STEROIDS derived from plants.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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.
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.
Conditions with excess LIPIDS in the blood.
An enzyme secreted from the liver into the plasma of many mammalian species. It catalyzes the esterification of the hydroxyl group of lipoprotein cholesterol by the transfer of a fatty acid from the C-2 position of lecithin. In familial lecithin:cholesterol acyltransferase deficiency disease, the absence of the enzyme results in an excess of unesterified cholesterol in plasma. EC 2.3.1.43.
Dioxygenase enzymes that specifically hydroxylate a PROLINE residue on the HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA.
A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).
A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter.
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.
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.
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.
Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES.
Elements of limited time intervals, contributing to particular results or situations.
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.
A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium Cl(-) anion.
An intermediate in the synthesis of cholesterol.
Proteins that bind to and transfer CHOLESTEROL ESTERS between LIPOPROTEINS such as LOW-DENSITY LIPOPROTEINS and HIGH-DENSITY LIPOPROTEINS.
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.
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.
A complex of polyene antibiotics obtained from Streptomyces filipinensis. Filipin III alters membrane function by interfering with membrane sterols, inhibits mitochondrial respiration, and is proposed as an antifungal agent. Filipins I, II, and IV are less important.
Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.
A drug-metabolizing, cytochrome P-450 enzyme which catalyzes the hydroxylation of aniline to hydroxyaniline in the presence of reduced flavoprotein and molecular oxygen. EC 1.14.14.-.
Uptake of substances through the lining of the INTESTINES.
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.
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.
Proteins prepared by recombinant DNA technology.
Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.
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.
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.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
An enzyme that catalyzes the hydrolysis of CHOLESTEROL ESTERS and some other sterol esters, to liberate cholesterol plus a fatty acid anion.
Established cell cultures that have the potential to propagate indefinitely.
Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A member of the P450 superfamily, this enzyme catalyzes the first oxidative step of the phenylpropanoid pathway in higher PLANTS by transforming trans-cinnamate into p-coumarate.
Presence or formation of GALLSTONES in the BILIARY TRACT, usually in the gallbladder (CHOLECYSTOLITHIASIS) or the common bile duct (CHOLEDOCHOLITHIASIS).
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.
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)
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
A triterpene that derives from the chair-boat-chair-boat folding of 2,3-oxidosqualene. It is metabolized to CHOLESTEROL and CUCURBITACINS.
A mitochondrial cytochrome P450 enzyme that catalyzes the side-chain cleavage of C27 cholesterol to C21 pregnenolone in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11A1 gene, catalyzes the breakage between C20 and C22 which is the initial and rate-limiting step in the biosynthesis of various gonadal and adrenal steroid hormones.
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.
A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS.
Unsaturated derivatives of the steroid androstane containing at least one double bond at any site in any of the rings.
Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.
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.
An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.
An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.
A diet that contributes to the development and acceleration of ATHEROGENESIS.
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.
Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.
A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues.
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Blocking of a blood vessel by CHOLESTEROL-rich atheromatous deposits, generally occurring in the flow from a large artery to small arterial branches. It is also called arterial-arterial embolization or atheroembolism which may be spontaneous or iatrogenic. Patients with spontaneous atheroembolism often have painful, cyanotic digits of acute onset.
Derivatives of the saturated steroid cholestane with methyl groups at C-18 and C-19 and an iso-octyl side chain at C-17.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
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.
Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.
Transport proteins that carry specific substances in the blood or across cell membranes.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.
A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.
An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Lipid-laden macrophages originating from monocytes or from smooth muscle cells.
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
Regular course of eating and drinking adopted by a person or animal.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.
A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.
A group of autosomal recessive disorders in which harmful quantities of lipids accumulate in the viscera and the central nervous system. They can be caused by deficiencies of enzyme activities (SPHINGOMYELIN PHOSPHODIESTERASE) or defects in intracellular transport, resulting in the accumulation of SPHINGOMYELINS and CHOLESTEROL. There are various subtypes based on their clinical and genetic differences.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
An enzyme that catalyzes the HYDROXYLATION of gamma-butyrobetaine to L-CARNITINE. It is the last enzyme in the biosynthetic pathway of L-CARNITINE and is dependent on alpha-ketoglutarate; IRON; ASCORBIC ACID; and OXYGEN.
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.
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
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.
Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.
A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.
Compounds based on 2-amino-4-hydroxypteridine.
A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.
This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.
A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.
Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A sterol regulatory element binding protein that regulates GENES involved in CHOLESTEROL synthesis and uptake.
An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.
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.
The processes whereby the internal environment of an organism tends to remain balanced and stable.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.
A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.
An autosomal recessive disorder of CHOLESTEROL metabolism. It is caused by a deficiency of 7-dehydrocholesterol reductase, the enzyme that converts 7-dehydrocholesterol to cholesterol, leading to an abnormally low plasma cholesterol. This syndrome is characterized by multiple CONGENITAL ABNORMALITIES, growth deficiency, and INTELLECTUAL DISABILITY.
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).
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Cholesterol substituted in any position by a keto moiety. The 7-keto isomer inhibits 3-hydroxy-3-methylglutaryl-CoA reductase activity and inhibits cholesterol uptake in the coronary arteries and aorta in vitro.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
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.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.
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.
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).
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.

Chinese hamster ovary cells require the coexpression of microsomal triglyceride transfer protein and cholesterol 7alpha-hydroxylase for the assembly and secretion of apolipoprotein B-containing lipoproteins. (1/481)

Due to the absence of microsomal triglyceride transfer protein (MTP), Chinese hamster ovary (CHO) cells lack the ability to translocate apoB into the lumen of the endoplasmic reticulum, causing apoB to be rapidly degraded by an N-acetyl-leucyl-leucyl-norleucinal-inhibitable process. The goal of this study was to examine if expression of MTP, whose genetic deletion is responsible for the human recessive disorder abetalipoproteinemia, would recapitulate the lipoprotein assembly pathway in CHO cells. Unexpectedly, expression of MTP mRNA and protein in CHO cells did not allow apoB-containing lipoproteins to be assembled and secreted by CHO cells expressing apoB53. Although expression of MTP in cells allowed apoB to completely enter the endoplasmic reticulum, it was degraded by a proteolytic process that was inhibited by dithiothreitol (1 mM) and chloroquine (100 microM), but resistant to N-acetyl-leucyl-leucyl-norleucinal. In marked contrast, coexpression of the liver-specific gene product cholesterol 7alpha-hydroxylase with MTP resulted in levels of MTP lipid transfer activity that were similar to those in mouse liver and allowed intact apoB53 to be secreted as a lipoprotein particle. These data suggest that, although MTP-facilitated lipid transport is not required for apoB translocation, it is required for the secretion of apoB-containing lipoproteins. We propose that, in CHO cells, MTP plays two roles in the assembly and secretion of apoB-containing lipoproteins: 1) it acts as a chaperone that facilitates apoB53 translocation, and 2) its lipid transfer activity allows apoB-containing lipoproteins to be assembled and secreted. Our results suggest that the phenotype of the cell (e.g. expression of cholesterol 7alpha-hydroxylase by the liver) may profoundly influence the metabolic relationships determining how apoB is processed into lipoproteins and/or degraded.  (+info)

The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil. (2/481)

Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body.  (+info)

High plasma cholesterol in drug-induced cholestasis is associated with enhanced hepatic cholesterol synthesis. (3/481)

In alpha-naphthylisothiocyanate-treated mice, plasma phospholipid (PL) levels were elevated 10- and 13-fold at 48 and 168 h, respectively, whereas free cholesterol (FC) levels increased between 48 h (17-fold) and 168 h (39-fold). Nearly all of these lipids were localized to lipoprotein X-like particles in the low-density lipoprotein density range. The PL fatty acyl composition was indicative of biliary origin. Liver cholesterol and PL content were near normal at all time points. Hepatic hydroxymethylglutaryl CoA reductase activity was increased sixfold at 48 h, and cholesterol 7alpha-hydroxylase activity was decreased by approximately 70% between 24 and 72 h. These findings suggest a metabolic basis for the appearance of abnormal plasma lipoproteins during cholestasis. Initially, PL and bile acids appear in plasma where they serve to promote the efflux of cholesterol from hepatic cell membranes. Hepatic cholesterol synthesis is then likely stimulated in the response to the depletion of hepatic cell membranes of cholesterol. We speculate that the enhanced synthesis of cholesterol and impaired conversion to bile acids, particularly during the early phase of drug response, contribute to the accumulation of FC in the plasma.  (+info)

Identification of a nuclear receptor for bile acids. (4/481)

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.  (+info)

CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene. (5/481)

Cholesterol 7alpha-hydroxylase is the first and rate-limiting enzyme in a pathway through which cholesterol is metabolized to bile acids. The gene encoding cholesterol 7alpha-hydroxylase, CYP7A, is expressed exclusively in the liver. Overexpression of CYP7A in hamsters results in a reduction of serum cholesterol levels, suggesting that the enzyme plays a central role in cholesterol homeostasis. Here, we report the identification of a hepatic-specific transcription factor that binds to the promoter of the human CYP7A gene. We designate this factor CPF, for CYP7A promoter binding factor. Mutation of the CPF binding site within the CYP7A promoter abolished hepatic-specific expression of the gene in transient transfection assays. A cDNA encoding CPF was cloned and identified as a human homolog of the Drosophila orphan nuclear receptor fushi tarazu F1 (Ftz-F1). Cotransfection of a CPF expression plasmid and a CYP7A reporter gene resulted in specific induction of CYP7A-directed transcription. These observations suggest that CPF is a key regulator of human CYP7A gene expression in the liver.  (+info)

Lipoprotein cholesterol uptake mediates up-regulation of bile-acid synthesis by increasing cholesterol 7alpha-hydroxylase but not sterol 27-hydroxylase gene expression in cultured rat hepatocytes. (6/481)

Lipoproteins may supply substrate for the formation of bile acids, and the amount of hepatic cholesterol can regulate bile-acid synthesis and increase cholesterol 7alpha-hydroxylase expression. However, the effect of lipoprotein cholesterol on sterol 27-hydroxylase expression and the role of different lipoproteins in regulating both enzymes are not well established. We studied the effect of different rabbit lipoproteins on cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase in cultured rat hepatocytes. beta-Migrating very-low-density lipoprotein (betaVLDL) and intermediate-density lipoprotein (IDL) caused a significant increase in the intracellular cholesteryl ester content of cells (2. 3- and 2-fold, respectively) at a concentration of 200 microgram of cholesterol/ml, whereas high-density lipoprotein (HDL, 50% v/v), containing no apolipoprotein E (apo E), showed no effect after a 24-h incubation. betaVLDL and IDL increased bile-acid synthesis (1. 9- and 1.6-fold, respectively) by up-regulation of cholesterol 7alpha-hydroxylase activity (1.7- and 1.5-fold, respectively). Dose- and time-dependent changes in cholesterol 7alpha-hydroxylase mRNA levels and gene expression underlie the increase in enzyme activity. Incubation of cells with HDL showed no effect. Sterol 27-hydroxylase gene expression was not affected by any of the lipoproteins added. Transient-expression experiments in hepatocytes, transfected with a promoter-reporter construct containing the proximal 348 nucleotides of the rat cholesterol 7alpha-hydroxylase promoter, showed an enhanced gene transcription (2-fold) with betaVLDL, indicating that a sequence important for a cholesterol-induced transcriptional response is located in this part of the cholesterol 7alpha-hydroxylase gene. The extent of stimulation of cholesterol 7alpha-hydroxylase is associated with the apo E content of the lipoprotein particle, which is important in the uptake of lipoprotein cholesterol. We conclude that physiological concentrations of cholesterol in apo E-containing lipoproteins increase bile-acid synthesis by stimulating cholesterol 7alpha-hydroxylase gene transcription, whereas HDL has no effect and sterol 27-hydroxylase is not affected.  (+info)

Selective uptake of cholesteryl ester from low density lipoprotein is involved in HepG2 cell cholesterol homeostasis. (7/481)

Low density lipoprotein (LDL) can follow either a holoparticle uptake pathway, initiated by the LDL receptor (LDLr), and be completely degraded, or it can deliver its cholesteryl esters (CE) selectively to HepG2 cells. Although high density lipoprotein-CE selective uptake has been shown to be linked to cell cholesterol homeostasis in nonhepatic cells, there is no available information on the effect of LDL-CE selective uptake on hepatic cell cholesterol homeostasis. In order to define the role of the LDL-CE selective uptake pathway in hepatic cell cholesterol homeostasis, we used a cellular model that expresses constitutively a LDLr antisense mRNA and that shows LDLr activity at 31% the normal level (HepG2-all cells). The addition of a specific antibody anti-LDLr (IgG-C7) reduces LDL protein degradation (LDLr activity) to 7%. This cellular model therefore reflects, above all, LDL-CE selective uptake activity when incubated with LDL. The inactivation of LDLr reduces LDL-protein association by 78% and LDL-CE association by only 43%. The LDL-CE selective uptake was not reduced by the inactivation of LDLr. The activities of the various enzymes involved in cell cholesterol homeostasis were measured in normal and LDLr-deficient cells during incubation in the absence or presence of LDL as a cholesterol source. Essentially, 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase (ACAT) activities responded to LDL in LDLr-deficient cells as well as in normal HepG2 cells. Inhibition of lysosomal hydrolysis with chloroquine abolished the effect measured on ACAT activity in the presence of LDL, suggesting that CE of LDL, but not free cholesterol, maintains cell cholesterol homeostasis. Thus, in HepG2 cells, when LDLr function is virtually abolished, LDL-CE selective uptake is coupled to cell cholesterol homeostasis.  (+info)

Bile acid synthesis in the Smith-Lemli-Opitz syndrome: effects of dehydrocholesterols on cholesterol 7alpha-hydroxylase and 27-hydroxylase activities in rat liver. (8/481)

The Smith-Lemli-Opitz syndrome (SLOS) is a congenital birth defect syndrome caused by a deficiency of 3beta-hydroxysterol Delta(7)-reductase, the final enzyme in the cholesterol biosynthetic pathway. The patients have reduced plasma and tissue cholesterol concentrations with the accumulation of 7-dehydrocholesterol and 8-dehydrocholesterol. Bile acid synthesis is reduced and unnatural cholenoic and cholestenoic acids have been identified in some SLOS patients. To explore the mechanism of the abnormal bile acid production, the activities of key enzymes in classic and alternative bile acid biosynthetic pathways (microsomal cholesterol 7alpha-hydroxylase and mitochondrial sterol 27-hydroxylase) were measured in liver biopsy specimens from two mildly affected SLOS patients. The effects of 7- and 8-dehydrocholesterols on these two enzyme activities were studied by using liver from SLOS model rats that were treated with the Delta(7)-reductase inhibitor (BM15.766) for 4 months and were comparable with more severe SLOS phenotype in plasma and hepatic sterol compositions. In the SLOS patients, cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase were not defective. In BM15.766-treated rats, both enzyme activities were lower than those in control rats and they were competitively inhibited by 7- and 8-dehydrocholesterols. Rat microsomal cholesterol 7alpha-hydroxylase did not transform 7-dehydrocholesterol or 8-dehydrocholesterol into 7alpha-hydroxylated sterols. In contrast, rat mitochondrial sterol 27-hydroxylase catalyzed 27-hydroxylation of 7- and 8-dehydrocholesterols, which were partially converted to 3beta-hydroxycholestadienoic acids. Addition of microsomes to the mitochondrial 27-hydroxylase assay mixture reduced 27-hydroxydehydrocholesterol concentrations, which suggested that 27-hydroxydehydrocholesterols were further metabolized by microsomal enzymes. These results suggest that reduced normal bile acid production is characteristic of severe SLOS phenotype and is caused not only by depletion of hepatic cholesterol but also by competitive inhibition of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by accumulated 7- and 8-dehydrocholesterols. Unnatural bile acids are synthesized mainly by the alternative pathway via mitochondrial sterol 27-hydroxylase in SLOS.  (+info)

Looking for online definition of 17alpha-hydroxylase in the Medical Dictionary? 17alpha-hydroxylase explanation free. What is 17alpha-hydroxylase? Meaning of 17alpha-hydroxylase medical term. What does 17alpha-hydroxylase mean?
7 alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylaseCYPVIIIB1cytochrome P450 8B1cytochrome P450, subfamily VIIIB (sterol 12-alpha- ...
The main objective of the present work was to characterize the response of human cholesterol synthesis that occurs within the normal range of cholesterol intake. Our results demonstrate modestly reduced cholesterogenesis with increasing dietary cholesterol levels as assessed by two techniques. Metabolic responses to increased dietary cholesterol potentially include reduced endogenous synthesis, decreased absorption, and increased biliary excretion of cholesterol.7 35 Feedback inhibition of cholesterol synthesis has been well described in animals,20 21 whereas the results of investigations in humans have been somewhat equivocal, with downregulation reported in some6 7 35 36 37 38 39 but not all22 23 24 40 41 42 studies. Nestel and Poyser7 fed 2 normolipidemic and 7 hyperlipidemic subjects diets with either 250 or 750 mg/d cholesterol for ,4 weeks. Cholesterol synthesis, as measured by sterol balance, was suppressed at the higher level of dietary cholesterol in 5 of 9 study participants, including ...
To study the effect of steroid hormones on bile acid synthesis by cultured rat hepatocytes, cells were incubated with various amounts of these compounds during 72 h and conversion of [4-14C]cholesterol into bile acids was measured. Bile acid synthesis was stimulated in a dose-dependent way by glucocorticoids, but not by sex steroid hormones, pregnenolone or the mineralocorticoid aldosterone in concentrations up to 10 microM. Dexamethasone proved to be the most efficacious inducer, giving 3-fold and 7-fold increases in bile acid synthesis during the second and third 24 h incubation periods respectively, at a concentration of 50 nM. Mass production of bile acids as measured by g.l.c. during the second day of culture (28-52 h) was 2.2-fold enhanced by 1 microM-dexamethasone. No change in the ratio of bile acids produced was observed during this period in the presence of dexamethasone. Conversion of [4-14C]7 alpha-hydroxycholesterol, an intermediate of the bile acid pathway, to bile acids was not ...
Principal Investigator:AOYAMA Yoritaka, Project Period (FY):1994 - 1995, Research Category:Grant-in-Aid for General Scientific Research (C), Research Field:食品科学・栄養科学
The synthesis and excretion of bile acids comprise the major pathway of cholesterol catabolism in mammals. Synthesis provides a direct means of converting cholesterol, which is both hydrophobic and insoluble, into a water-soluble and readily excreted molecule, the bile acid. The biosynthetic steps t …
triglycerides-207.20,LDL cholesterol-65.26,VLDL cholesterol-41.44 please advise me Hello Swati, I read your message carefully and understood your medical
TY - JOUR. T1 - Cloning and regulation of cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. AU - Jelinek, D. F.. AU - Andersson, S.. AU - Slaughter, C. A.. AU - Russell, D. W.. N1 - Copyright: Copyright 2007 Elsevier B.V., All rights reserved.. PY - 1990. Y1 - 1990. N2 - The rate-limiting step in bile acid biosynthesis is catalyzed by the microsomal cytochrome P-450 cholesterol 7α-hydroxylase (7α-hydroxylase). The expression of this enzyme is subject to feedback regulation by sterols and is thought to be coordinately regulated with enzymes in the cholesterol supply pathways, including the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase and synthase. Here we report the purification of rat 7α-hydroxylase and the determination of a partial amino acid sequence. Oligonucleotides derived from peptide sequence were used to clone a full-length cDNA encoding 7α-hydroxylase. DNA sequence analysis of the cDNA revealed a 7α-hydroxylase ...
Upregulation of hepatic bile acid synthesis via fibroblast growth factor 19 is defective in gallstone disease but functional in overweight ...
CsA-treated animals showed a significant reduction in hepatic tissue abundance of cholesterol 7α-hydroxylase. This enzyme is the rate-limiting step in cholesterol conversion to bile acid, which is the principal pathway of cholesterol catabolism. Therefore, its down-regulation by CsA therapy can potentially contribute to elevation of cholesterol level. In an earlier study, Princen et al. (1991)demonstrated that CsA blocks bile acid synthesis by cultured hepatocytes in vitro. Down-regulation of hepatic cholesterol 7α-hydroxylase shown in the CsA-treated animals here provides the molecular basis of the in vitro studies by Princen et al. (1991). Intracellular concentration of free cholesterol exerts a direct regulatory role on hepatic cholesterol 7α-hydroxylase expression in the liver (Russell and Setchell, 1992). Down-regulation of cholesterol 7α-hydroxylase found in our CsA-treated animals may be due to depressed intracellular free cholesterol concentration noted in these animals.. In contrast ...
Perwad F, Zhang MY, Tenenhouse HS, Portale AA. Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Renal Physiol. 2007 Nov; 293(5):F1577-83 ...
Bile acid synthesis defects may manifest in the neonatal period or later. This panel is specifically designed to cover the genes which lead to neonatal or infantile onset of symptoms. The Jaundice NGS Panel is an option for those cases which present with jaundice and an unclear cause.
In article ,43scem$q40 at intruder.smcvt.edu,, t_cleary at smcvax.smcvt.edu wrote: , I NEED HELP. I AM A SENIOR AND DOING A RESEARCH PROJECT INVOLVING CHOLESTEROLDETERMINATION IN LIVER CELLS. I HAVE LOOKED ALMOST EVERYWHERE IN THE LITERATUREAND HAVE FOUND NOTHING. I NEED A PROCEDURE THAT EITHER DOES NOT INVOLVE , CENTRIFUGING OR INVOLVES CENTRIFUGING BUT ONLY UP TO 10,000g. If anyone , can help me with this it would be greatly appreciated. , Thank you, , Tabitha Cleary Sigma sells a cholesterol kit (cat # 352-20) with standards also available. It comes in several sizes, but is not cheap. It is a very simple assay and although designed for plasma, is easily used for liver if you extract the lipids first. e-mail me if you need more info. Darren -- Darren Fast fast at biochem.wisc.edu Dept of Biochemistry University of Wisconsin-Madison (608)-262-4705 ...
Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (
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.[6] 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. In this way, a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high. FXR has also been found to be important in regulation of hepatic triglyceride levels.[7] Studies have also shown the FXR to ...
TY - JOUR. T1 - On the stereospecificity of microsomal 26-hydroxylation in bile acid biosynthesis.. AU - Gustafsson, J.. AU - Sjöstedt, S.. PY - 1978/1/10. Y1 - 1978/1/10. N2 - The stereospecificity of microsomal 26 -hydroxylation in bile acid biosynthesis was studied. Cholesterol was biosynthesized from [2-14C] mevalonate by a rat liver preparation. The cholesterol was converted stepwise into 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid by microsomal and soluble fractions of rat liver homogenate. The 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid was decarboxylated chemically and the carbon dioxide was assayed for 14C. The amount of radioactivity in the liberated carbon dioxide was assayed for 14C. The amount of radioactivity in the liberated carbon dioxide was such as to indicate complete stereospecificity of the microsomal 26 -hydroxylase system. The system hydroxylates the methyl group in position C-26 (the 25-pro-R methyl group) and its ...
In addition to their well-known function as dietary lipid detergents, bile acids have emerged as important signalling molecules that regulate energy homeostasis. Recent studies have highlighted that disrupted bile acid metabolism is associated with metabolism disorders such as dyslipidaemia, intestinal chronic inflammatory diseases and obesity. In particular, type 2 diabetes (T2D) is associated with quantitative and qualitative modifications in bile acid metabolism. Bile acids bind and modulate the activity of transmembrane and nuclear receptors (NR). Among these receptors, the G-protein-coupled bile acid receptor 1 (TGR5) and the NR farnesoid X receptor (FXR) are implicated in the regulation of bile acid, lipid, glucose and energy homeostasis. The role of these receptors in the intestine... in energy metabolism regulation has been recently highlighted. More precisely, recent studies have shown that FXR is important for glucose homeostasis in particular in metabolic disorders such as T2D and ...
Abstract CYP27B1 encodes mitochondrial 1a-hydroxylase, which converts 25-hydroxyvitamin D to its active 1,25- dihydroxylated metabolite. We tested the hypothesis that common variants in the CYP27B1 promoter are associated with fracture risk. The study was designed as a populationbased genetic association study, which involved 153 men and 596 women aged 65101 years, who had been followed for 2.2 years (range 0.15.5) between 1999 and 2006. During the follow-up period, the incidence of fragility fractures was ascertained. Bone ultrasound attenuation (BUA) was measured in all individuals, as were serum 25-hydroxyvitamin D and PTH concentrations; 86% subjects had vitamin D insufficiency. Genotypes were determined for the 1260C[A (rs10877012) and ?2838T[C (rs4646536) CYP27B1 polymorphisms.Areporter gene assay was used to assess functional expression of the 1260C[A CYP27B1 variants. The association between genotypes and fracture risk was analyzed by Coxs proportional hazards model. We found that ...
Examples of orphan receptors are found in the G protein-coupled receptor (GPCR)[2][3][4] and nuclear receptor[5][6][7] families. If an endogenous ligand is found, the orphan receptor is adopted or de-orphanized[8]. An example is the nuclear receptor Farnesoid X receptor (FXR) and the GPCR TGR5/GPCR19/G protein-coupled bile acid receptor, both of which are activated by bile acids.[9] Adopted orphan receptors in the nuclear receptor group include FXR, liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). Another example of an orphan receptor site is the PCP binding site in the NMDA receptor,[10] a type of ligand-gated ion channel. This site is where the recreational drug PCP works, but no endogenous ligand is known to bind to this site. GPCR orphan receptors are usually given the name GPR followed by a number, for example GPR1. In the GPCR family, nearly 100 receptor-like genes remain orphans.[11] ...
AIMS: To investigate expression of nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) as a diagnostic tool to improve grading of dysplasia in Barretts oesophagus patients. METHODS AND RESULTS: Immunostaining was analysed on a total of 192 biopsy samples of 22 Barretts patients with no dysplasia (ND), 17 with low-grade dysplasia (LGD), 20 high-grade dysplasia (HGD) and 24 with adenocarcinoma (AC). Nuclear FXR expression was observed in 15 of 22 (68%) ND cases versus none of 19 HGD; 3 of 17 (18%); LGD; 5 of 60 (8%) patients with AC (P,0 ...
AIMS: To investigate expression of nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) as a diagnostic tool to improve grading of dysplasia in Barretts oesophagus patients. METHODS AND RESULTS: Immunostaining was analysed on a total of 192 biopsy samples of 22 Barretts patients with no dysplasia (ND), 17 with low-grade dysplasia (LGD), 20 high-grade dysplasia (HGD) and 24 with adenocarcinoma (AC). Nuclear FXR expression was observed in 15 of 22 (68%) ND cases versus none of 19 HGD; 3 of 17 (18%); LGD; 5 of 60 (8%) patients with AC (P,0 ...
Senior Brandeis research scientist Daniel Perlman 68 has discovered a way to make phytosterol molecules from plants dispersible in beverages and foods that are consumed by humans, potentially opening the way to dramatic reductions in human cholesterol levels.. A U.S. patent (number 8,460,738) on the new process and composition was issued on June 11. Phytosterols in plants and cholesterol molecules in animals are highly similar and when both are dispersed together they are attracted to one another. When they mix in the gut of an animal, the cholesterol molecules are competitively inhibited from passing into the blood stream and instead are excreted.. The ability of phytosterols to reduce cholesterol levels in animals has been recognized since the 1950s, but practical application of this knowledge was difficult because phytosterols are not naturally water-soluble, and they are only poorly soluble in fatty substances. Perlman and K.C. Hayes, professor emeritus of biology and former director of the ...
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [From RefSeq ...
We investigated the effect of increasing dietary cholesterol on bile acid pool sizes and the regulation of the two bile acid synthetic pathways (classic, via cholesterol 7α-hydroxylase, and alternative, via sterol 27-hydroxylase) in New Zealand white rabbits fed 3 g cholesterol/per day for up to 15 days. Feeding cholesterol for one day increased hepatic cholesterol 75% and cholesterol 7α-hydroxylase activity 1.6 times without significant change of bile acid pool size or sterol 27-hydroxylase activity. After three days of cholesterol feeding, the bile acid pool size increased 83% (P < 0.01), and further feeding produced 10%-20% increments, whereas cholesterol 7α-hydroxylase activity declined progressively to 60% below baseline. In contrast, sterol 27-hydroxylase activity rose 58% after three days of cholesterol feeding and remained elevated with continued intake. Bile drainage depleted the bile acid pool and stimulated downregulated cholesterol 7α-hydroxylase activity but did not affect ...
Title:Medicinal Chemistry and Pharmacological Effects of Farnesoid X Receptor (FXR) Antagonists. VOLUME: 14 ISSUE: 19. Author(s):Christina Lamers, Manfred Schubert-Zsilavecz and Daniel Merk. Affiliation:Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt (Main), Germany.. Keywords:Atherosclerosis, cancer, FXR antagonists, FXR knockout, glucose homeostasis, guggulsterone, lipid homeostasis, liver disorders, metabolic disorders, selective bile acid receptor modulators (SBARMs).. Abstract:The nuclear bile acid sensor farnesoid X receptor (FXR) constitutes a rising target for the treatment of a variety of diseases including metabolic disorders, inflammation and certain forms of cancer. While the research on FXR agonists has yielded many compounds and first clinical candidates, only few FXR antagonists have been discovered so far and the knowledge about their in vivo effects is quite narrow. We have evaluated available in vitro and in vivo studies ...
A research scientist from Brandeis University has found a way to make phytosterol molecules from plants dispersible in beverages and foods that are consumed by humans. Daniel Perlman reports that this new formula could potentially open the way to dramatic reductions in human cholesterol levels. A US patent has been filed on the new process and composition. Perlman has developed a method which changes the behaviour of phytosterols in liquids. Previously dispersing phytosterols in water has been problematic. The new technique changes the behaviour by forming a new complex in which glycerin molecules attach to phytosterol molecules. In a press release the scientist describes the process, saying: Phytosterols and glycerin are heated together to a temperature at which the water molecule that usually attaches to each phytosterol molecule boils off and is replaced by a glycerin molecule. Because glycerin molecules have multiple places at which water molecules can be attached and because glycerin also ...
Information on Congenital bile acid synthesis defect, type 1, which may include symptoms, causes, inheritance, treatments, orphan drugs, associated orgs, and other relevant data.
The liver receptor homolog-1 (LRH-1) also known as NR5A2 (nuclear receptor subfamily 5, group A, member 2) is a protein that in humans is encoded by the NR5A2 gene.[1][2] LRH-1 is a member of the nuclear receptor family of intracellular transcription factors. LRH-1 plays a critical role in the regulation of development, cholesterol transport, bile acid homeostasis and steroidogenesis.[3][4][5] LRH-1 is important for maintaining pluripotence of stem cells during embryonic development.[6] ...
The relative representation of each mutant was determined by calculating the fold change (sequence reads/insertion in cholesterol divided by sequence reads/insertion in glycerol) for each gene. Statistical significance was determined by t-test. Each insertion site in each replicate sample was treated as a separate data point. The hyperbola used for defining genes specifically required for growth in cholesterol was defined by the formula, y = 3.8/x+0.7. Genes above this line are annotated as required for growth on cholesterol. - Griffin JE, Gawronski JD, Dejesus MA, Ioerger TR, Akerley BJ, Sassetti CM, High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog (2011) 7(9). ...
Outlines  Overview and Functions  Liver cholesterol pool  Structure and Types  Synthesis and Regulation  Bile acids and salts  Enterohepatic circulation
This originally started happening back in September. He has had, maybe 6 since then. This last one was probably the scariest. I ran blood work as well as a thyroid test, and everything...I repeat everything, came back normal. I was hoping we would get an answer from the blood work, we didnt. Now we are onto step two, which is the Bile-Acid Test, it checks his liver function. If this doesnt turn out, we still have a halter test, which checks hearth function, as well as a CT or something of the short to check out his brain to see if it is seizure activity ...
The ingredients in Lipitrol work together to support optimal cholesterol metabolism and to maintain normal range cholesterol levels. �
Bile acid synthesis, determined by conversion of [4-14C]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52% (rat) and 45% (human) inhibition of 10 microM. The decreased bile acid production in rat hepatocytes was due only to a fall in the synthesis of beta-muricholic and chenodeoxycholic acids (-64% at 10 microM-cyclosporin A), with no change in the formation of cholic acid. In isolated rat liver mitochondria, 26-hydroxylation of cholesterol was potently inhibited by the drug (concn. giving half-maximal inhibition = 4 microM). These results suggest that cyclosporin A blocks the alternative pathway in bile acid synthesis, which leads preferentially to the formation of chenodeoxycholic acid. ...
Background: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor lacking DNA binding domain. SHP directly modulates the activities of other nuclear receptors and regulates a variety of cellular events such as cell differentiation, proliferation, and metabolism in various tissues. However, the role of SHP in heart has not yet been elucidated. Thus, in this study, we tried to investigate the functional roles of SHP in heart physiology and in the development of cardiac hypertrophy.. Methods and Results: We observed that SHP knock-out mice elicited cardiac hypertrophic features determined by heart weight to body weight or to tibia length ratios. Fetal genes, such as atrial natriuretic factor (ANF) or beta myosin heavy chain (βMHC) were significantly up-regulated in SHP knockout mice heart. In neonatal rat ventricular cardiomyocytes (NRVCs), phenylephrine (PE) reduced promoter activation of SHP and decreased protein level of SHP. Adenovirus-mediated over-expression of SHP ...
We have been told for years that cholesterol levels being too high are problematic, that it can contribute to heart disease and strokes. In fact, this is true for many people. However, what has gone unrecognized or ignored for many years is that too low cholesterol can be just as detrimental often leading to a myriad of mental health and disease conditions. There is a dynamic balance of all things in the body that must be achieved for optimal health to manifest, and cholesterol is a critically important component of that balance.. Sonic Cholesterol is an excellent choice for reviving low cholesterol levels:. Sonic Cholesterol is a pure and potent nutritional supplement designed specifically to support healthy cholesterol levels.. Sonic Cholesterol is the only cholesterol supplement on the market designed to help raise cholesterol to normal levels.. To learn more about the benefits of Sonic Cholesterol, the dangers of low cholesterol, and how to obtain your own supply of Sonic Cholesterol make ...
Bringing down cholesterol is imperative for everybody, including more youthful, moderately aged, and more established grown-ups, and individuals with or without coronary illness and/or stroke. Bringing down cholesterol is amazingly imperative key to diminishing the danger of coronary illness. Elevated amounts of LDL are connected with an expanded danger of coronary illness. Lower levels of LDL cholesterol mean a lower danger of coronary illness. Most specialists propose cholesterol levels ought to stay under 200 mg/dl. Bringing cholesterol is prescribed down to lead a more sound life and fundamental. Bringing down cholesterol is only one approach to take care of your heart. Bringing down cholesterol is really very basic, and doesnt oblige surgery or medications with solid way of life, actually bringing down cholesterol is simple since it aides standardize your cholesterol, normally and securely. One of the most straightforward approaches to beginning bringing cholesterol is down to farthest ...
Need to lower cholesterol? First, you must understand what it is and why its high. Cholesterol is a waxy molecule produced in the liver. Its a building block used all over the body to make neurotransmitters in your brain, hormones like testosterone/estrogens/progesterone/vitamin D (hormones with a cholesterol base are called steroid hormones), and its a component of every cell membrane in your body.. Remember, you cant pee in just one end of the pool. When you take a drug to lower cholesterol, every system that depends on cholesterol is affected. The side effects of memory loss, muscle pain, liver damage, and type 2 diabetes reflect the fundamental importance of cholesterol as a building block all over the body.. Cholesterol is made in the liver. Sooooo, why is the heart doctor giving you a drug to treat your liver. The reason is that its not really heart disease that causes heart attacks. These events, as well as most strokes, are caused by years of blood vessel inflammation. The final ...
Low prices on Cholesterol Support! Support healthy cholesterol levels already within the normal range*. Cholesterol can be both good and bad. LDL is usually referred to as bad cholesterol and HDL is good cholesterol. Numerous natural ingredients may help support healthy cholesterol levels already within the normal range.
Cholesterol is necessary to aid in body function, but sometimes we collect too much of the wrong kind of cholesterol. It is important to understand the differences between good and bad cholesterol and how you can control your cholesterol levels. (Tips.Net)
Catalog #: P2010002 - 250 U Cholesterol oxidase is a flavoprotein involved in the first step of cholesterol catabolism. The enzyme first oxidizes cholesterol to cholest-5-en-3-one then isomerizes it to cholest-4-en-3-one while producing hydrogen peroxide H2O2. Available in a 250 Units and custom bulk sizes. Live Enquiry about this product via Text/SMS: 1-858-900-3210 (8 am - 8 pm PST ...
Boost Your Good Cholesterol - 15 Heart-Healthy Foods to Boost Your Good Cholesterol - Youve probably heard that HDL cholesterol and LDL cholesterol = bad.
Real name: Unknown. Status: Inactive. Series: Cholesterol Man appeared in the Blorg Trek series. Notes: Cholesterol Man is an inactive character, available for use. Known powers: Cholesterol Man can increase the fat levels of anyone he touches, to a point where the victim becomes ridiculously bloated. His thick layer of fat prevents him from being harmed by most attacks. Description: Obese is an understatement. So is chubby. The man is huge. Cholesterol Man wears a jogging suit (he tries, unsuccessfully, to lose weight in his spare time). ...
Pregnenolone (17-hydroxy), 1 ml. 17a-OH-Pregnenolone is an intermediate in steroid biosynthesis and is produced through hydroxylation of|br /|pregnenolone by the enzyme 17-alpha-hydroxylase.
Cholesterol is a waxy fat-like substance found in your body. Your body needs cholesterol to keep your cells healthy. Too much LDL (bad) cholesterol causes plaque to collect in your arteries.
We can help you control your cholesterol to avoid heart and circulation problems. Plus discover the types of cholesterol and what level readings mean.
Cholesterol is a type of fat found in your blood. The body needs some cholesterol, but too much can be a problem. Discover more about cholesterol in this article for teens.
Cholesterol is a type of fat found in your blood. The body needs some cholesterol, but too much can be a problem. Discover more about cholesterol in this article for teens.
Cholesterol is a type of fat found in your blood. The body needs some cholesterol, but too much can be a problem. Discover more about cholesterol in this article for teens.
Cholesterol testing can play an important role in supporting overall health, but many people who are at risk for cardiovascular complications do not pursue this screening because they have a lack of understanding of how cholesterol affects their well-being. Individuals should improve their knowledge about the dangers of cholesterol in order to support well-being, experts say ...
How Can You Remember to Take Your Cholesterol Medications? - Our experts discuss strategies for staying on top of your cholesterol medication while away from home.
How to Reduce Cholesterol Without Medicines. When there are more natural ways to keep your bad cholesterol down, taking medications seems inorganic and foreign. If you simply want to manage your cholesterol but dont want the fuss of...
Most of us have heard about good cholesterol and bad cholesterol. But its not the cholesterol that causes harm, its the particles that carry it. And routine
The only critical risk factor for artery plaque buildup is cholesterol. Get the latest research on cholesterol in free, easy to understand videos.
Interested in lowering your cholesterol? Find out what your cholesterol test results mean & get plenty of advice about taking care of your heart here.
Think youre too young to worry about your cholesterol levels? Its never too early to learn the facts about cholesterol - the good, the bad and the ugly.
The cholesterol in your blood comes from the foods you eat and your liver. Your liver makes all of the cholesterol your body needs.
The cholesterol in your blood comes from the foods you eat and your liver. Your liver makes all of the cholesterol your body needs.
In Step 3 of our Ultimate Cholesterol Lowering Plan youll start adding some key foods into your diet which actually help to lower your cholesterol.
An excess of cholesterol can build up in the arteries, narrowing them and slowing or blocking blood flow to the heart. Take this quiz to learn more about cholesterol and its role in your health.
An excess of cholesterol can build up in the arteries, narrowing them and slowing or blocking blood flow to the heart. Take this quiz to learn more about cholesterol and its role in your health.
Define Cholesterol. Cholesterol is a soft and waxy fatty substance present in the bloos streams and cells of both humans and animals.
The risks of high cholesterol and cancer can be lowered by following these rules. Learn more about cholesterol and cancer how to lower your risks from Discovery Health.
We offer cholesterol and cardiac tests in California. Visit one of our conveniently located test labs for heart and cholesterol screening near Yuba City. Order online or call (530) 771-6497.
We offer cholesterol and cardiac tests in California. Visit one of our conveniently located test labs for heart and cholesterol screening near Barstow. Order online or call (760) 507-2786.
You know you should manage your cholesterol, but a busy lifestyle can make that tough to do. A health care provider offers insight on some common obstacles to controlling your cholesterol, as well as ways to break through them.
Contrary to popular belief, not all cholesterol is bad for you! If youve ever asked yourself, What is good cholesterol? Simplefill has the answers.
Question - Would it still be important to try to reduce cholesterol ?. Ask a Doctor about Cholesterol, Ask a Critical Care Specialist
Triglycerides also play an important role in clearing the toxins from the blood, as in cases of severe sepsis! (So high TGs means its a normal response to infection ...
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Cholesterol is a chemical compound that the body requires as a building block for cell membranes ... greater your risk for developing heart disease
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Cholesterol is a fatty substance that is vital for our body and its functioning. But even very useful thing always should be into the measure, and the leve
Many adults under 40 may not need to have routine cholesterol screenings, a new study suggests. To come to this conclusion, the researchers looked at the real w
Are new medicines for people with out-of-control cholesterol wildly overpriced? Its a question thats sparking debate among consumers and providers of care.
iMedPub is a new approach to scientific publishing. As an open service to scientists, it is driven by researchers for researchers, while serving the interests of the general public Cholesterol | .
Cholesterol blood tests are used to determine an individuals risk of developing heart disease. Such tests typically look for the total quantity of...
... or alpha-) methylacyl-CoA racemase (AMACR) deficiency; cholesterol 7 alpha-hydroxylase (CYP7A1) deficiency. The most common ... sterol 27-hydroxylase (presenting as cerebrotendinous xanthomatosis, CTX) deficiency; 2- ( ... Cholic acid downregulates cholesterol-7-α-hydroxylase (rate-limiting step in bile acid synthesis), and cholesterol does the ... where it is synthesized from cholesterol. These two major bile acids are roughly equal in concentration in humans. Derivatives ...
In an animal model, THAP was reported to enhance cholesterol 7 alpha-hydroxylase (CYP7A1) activity. THAP is also used as a ... "Induction of human cholesterol 7α-hydroxylase in HepG2 cells by 2,4,6-trihydroxyacetophenone". European Journal of Pharmacology ... THAP is a chemical precursor that can be used to form part of the backbone of 5,7-dihydroxyflavones like noreugenin, apigenin, ...
Lavery, Daniel J.; Schibler, Ueli (1993). "Circadian transcription of the cholesterol 7 alpha hydroxylase gene may involve the ... 7 (10): 1871-84. doi:10.1101/gad.7.10.1871. PMID 8405996. Gorski, K.; Carneiro, M.; Schibler, U. (1986). "Tissue-specific in ...
Do R, Kiss RS, Gaudet D, Engert JC (January 2009). "Squalene synthase: a critical enzyme in the cholesterol biosynthesis ... Ness GC, Zhao Z, Keller RK (June 1994). "Effect of squalene synthase inhibition on the expression of hepatic cholesterol ... As a squalene synthase inhibitor, zaragozic acid produces lower plasma cholesterol levels in primates. Treatment of rats with ... and cholesterol 7 alpha hydroxylase". Arch. Biochem. Biophys. 311 (2): 277-85. doi:10.1006/abbi.1994.1238. PMID 7911291. ...
"A prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4 α that regulates the cholesterol ... is a corepressor of human liver receptor homolog-1 and suppresses the transcription of the cholesterol 7-alpha-hydroxylase gene ... 225 (3): 351-7. doi:10.1002/dvdy.10163. PMID 12412020. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and ... 7α-hydroxylase gene". J. Biol. Chem. 281 (15): 10081-8. doi:10.1074/jbc.M513420200. PMC 1785292. PMID 16488887. Schneider M, ...
"Correlation of farnesoid X receptor coactivator recruitment and cholesterol 7alpha-hydroxylase gene repression by bile acids". ... Peroxisome proliferator-activated receptor gamma coactivator 1-alpha and Retinoid X receptor alpha. A number of ligands for FXR ... Kalaany NY, Mangelsdorf DJ (2006). "LXRS and FXR: the yin and yang of cholesterol and fat metabolism". Annual Review of ... One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate- ...
Minor pathways initiated by 25-hydroxylase in the liver and 24-hydroxylase in the brain also may contribute to bile acid ... In so doing, more endogenous cholesterol is shunted into the production of bile acids, thereby lowering cholesterol levels. The ... termed alpha (α; displayed as a dashed line). All bile acids have a 3-hydroxyl group, derived from the parent molecule, ... The relationship of bile acids to cholesterol saturation in bile and cholesterol precipitation to produce gallstones has been ...
... cholesterol side-chain cleavage enzyme MeSH D08.244.453.915.400 - 25-hydroxyvitamin d3 1-alpha-hydroxylase MeSH D08.244.453.915 ... steroid 11-beta-hydroxylase MeSH D08.244.453.915.730 - steroid 12-alpha-hydroxylase MeSH D08.244.453.915.737 - steroid 16-alpha ... steroid 12-alpha-hydroxylase MeSH D08.811.682.690.708.170.915.737 - steroid 16-alpha-hydroxylase MeSH D08.811.682.690.708.170. ... steroid 12-alpha-hydroxylase MeSH D08.811.682.690.708.783.737 - steroid 16-alpha-hydroxylase MeSH D08.811.682.690.708.783.745 ...
In addition, production of Apo A1 and ATP binding cassette A1 is up-regulated, leading to increased reverse cholesterol ... These stimulate peroxisome proliferator activated receptor (PPAR) alpha, which controls the expression of gene products that ... They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore ... Fibrates decrease the synthesis of bile acid by down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase ...
... cholesterol side-chain cleavage enzyme MeSH D12.776.422.220.453.915.400 - 25-hydroxyvitamin d3 1-alpha-hydroxylase MeSH D12.776 ... steroid 12-alpha-hydroxylase MeSH D12.776.422.220.453.915.737 - steroid 16-alpha-hydroxylase MeSH D12.776.422.220.453.915.748 ... steroid 17-alpha-hydroxylase MeSH D12.776.422.220.453.915.760 - steroid 21-hydroxylase MeSH D12.776.422.512.380.440 - ... alpha 1-antichymotrypsin MeSH D12.776.377.715.085.085 - alpha 1-antitrypsin MeSH D12.776.377.715.085.100 - alpha-macroglobulins ...
Boyd GS, Grimwade AM, Lawson ME (1973). "Studies on rat-liver microsomal cholesterol 7alpha-hydroxylase". Eur. J. Biochem. 37 ( ... In enzymology, a cholesterol 7alpha-monooxygenase (EC 1.14.13.17) is an enzyme that catalyzes the chemical reaction cholesterol ... Mitton JR, Scholan NA, Boyd GS (1971). "The oxidation of cholesterol in rat liver sub-cellular particles The cholesterol-7- ... alpha-Hydroxylase enzyme system". Eur. J. Biochem. 20 (4): 569-79. doi:10.1111/j.1432-1033.1971.tb01429.x. PMID 4397276. ...
Davis RA, Miyake JH, Hui TY, Spann NJ (Apr 2002). "Regulation of cholesterol-7alpha-hydroxylase: BAREly missing a SHP". Journal ... Li T, Chanda D, Zhang Y, Choi HS, Chiang JY (Apr 2010). "Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription ... Li T, Chanda D, Zhang Y, Choi HS, Chiang JY (Apr 2010). "Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription ... Gbaguidi GF, Agellon LB (2004-01-01). "The inhibition of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter by ...
Evidence that the enzyme involved is different from cholesterol 7 alpha-hydroxylase". European Journal of Biochemistry. 224 (2 ... 25-hydroxycholesterol+7alpha-hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal ... Li-Hawkins J, Lund EG, Bronson AD, Russell DW (June 2000). "Expression cloning of an oxysterol 7alpha-hydroxylase selective for ... 25-hydroxycholesterol 7alpha-hydroxylase (EC 1.14.13.100, 25-hydroxycholesterol 7alpha-monooxygenase, CYP7B1, CYP7B1 oxysterol ...
Other hydroxylating agents include flavins, alpha-ketoglutarate-dependent hydroxylases, and some diiron hydroxylases. The ... 17α-Hydroxylase Cholesterol 7 alpha-hydroxylase Dopamine β-hydroxylase Phenylalanine hydroxylase Tyrosine hydroxylase One ... multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase and lysyl 5-hydroxylase, respectively. These reactions require ... In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. A C-H bond is converted to an ...
The demethylated products of the CYP51 reaction are vital intermediates in pathways leading to the formation of cholesterol in ... Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14). 1.14.11: 2-oxoglutarate. *Prolyl hydroxylase ... Tuck SF, Patel H, Safi E, Robinson CH (June 1991). "Lanosterol 14 alpha-demethylase (P45014DM): effects of P45014DM inhibitors ... alpha helix and the β4 loop.[8][9] Finally, the active site contains a heme prosthetic group in which the iron is tethered to a ...
... belongs to the family of ferrous iron and alpha-ketoglutarate-dependent hydroxylases superfamily.,[6] and is active as a ... Cholesterol 7 alpha-hydroxylase. *Methane monooxygenase. *3A4. *Lanosterol 14 alpha-demethylase. *24-hydroxycholesterol 7α- ... The catalytic activity of PHF8 depends on molecular oxygen,[7] a fact considered important with respect to reports on increased ... histone lysine demethylase with selectivity for the di-and monomethyl states.[7] ...
Macheroux P, Plattner HJ, Romaguera A, Diekmann H (1993). "FAD and substrate analogs as probes for lysine N6-hydroxylase from ... Cholesterol 7 alpha-hydroxylase. *Methane monooxygenase. *3A4. *Lanosterol 14 alpha-demethylase. *24-hydroxycholesterol 7α- ... Marrone L, Siemann S, Beecroft M, Viswanatha T (1996). "Specificity of lysine:N-6-hydroxylase: A hypothesis for a reactive ... This enzyme is also called lysine N6-hydroxylase. This enzyme participates in lysine degradation. ...
Capyk JK, D'Angelo I, Strynadka NC, Eltis LD (April 2009). "Characterization of 3-ketosteroid 9{alpha}-hydroxylase, a Rieske ... indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis". The Journal of ... Capyk JK, Casabon I, Gruninger R, Strynadka NC, Eltis LD (November 2011). "Activity of 3-ketosteroid 9α-hydroxylase (KshAB) ... 3-ketosteroid 9alpha-monooxygenase (EC 1.14.13.142, KshAB, 3-ketosteroid 9alpha-hydroxylase) is an enzyme with systematic name ...
cholesterol 24-hydroxylase. 1 subfamily, 1 gene. CYP46A1 CYP51. cholesterol biosynthesis. 1 subfamily, 1 gene, 3 pseudogenes. ... steroid biosynthesis, 17-alpha hydroxylase. 1 subfamily, 1 gene. CYP17A1 CYP19. steroid biosynthesis: aromatase synthesizes ... steroid 20α-hydroxylase, steroid 22-hydroxylase, cholesterol side-chain scission). ... CYP27A1 (bile acid biosynthesis), CYP27B1 (vitamin D3 1-alpha hydroxylase, activates vitamin D3), CYP27C1 (unknown function) ...
... cholesterol homeostasis, cholesterol O-acyltransferase activity, cholesterol 25-hydroxylase activity, cholesterol 7-alpha- ... cholesterol binding, cholesterol biosynthetic process, cholesterol catabolic process, response to cholesterol, cellular ... intestinal cholesterol absorption, cholesterol transport, lysosome to ER cholesterol transport, cholesterol transfer activity, ... cholesterol import, cholesterol metabolic process, cholesterol biosynthetic process via 24,25-dihydrolanosterol, cholesterol ...
Li-Hawkins J, Lund EG, Turley SD, Russell DW (June 2000). "Disruption of the oxysterol 7alpha-hydroxylase gene in mice". J. ... This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic ... Wu Z, Martin KO, Javitt NB, Chiang JY (2000). "Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene ... Tang W, Norlin M (2006). "Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate cancer LNCaP cells". ...
... cholestanetriol 26-hydroxylase, sterol 27-hydroxylase, sterol 26-hydroxylase, cholesterol 27-hydroxylase, CYP27A, CYP27A1, and ... 12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid". J. Biol. Chem. 268 (15): 11079-85. PMID ... 12alpha-triol 26-hydroxylase, 5beta-cholestane-3alpha,7alpha,12alpha-triol hydroxylase, ... Usui E, Noshiro M, Okuda K (1990). "Molecular cloning of cDNA for vitamin D3 25-hydroxylase from rat liver mitochondria". FEBS ...
2004). "Mechanisms of cholesterol and sterol regulatory element binding protein regulation of the sterol 12alpha-hydroxylase ... Li Y, Mezei O, Shay NF (2007). "Human and murine hepatic sterol-12-alpha-hydroxylase and other xenobiotic metabolism mRNA are ... CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) also known as sterol 12-alpha-hydroxylase is a protein which in ... In the intestine these bile acids affect the solubility of cholesterol and other lipids, promoting their absorption. CYP8B1 is ...
At the carboxyl terminal of the peptide chain there's a short alpha helix domain that allows tetramerization.[15] The central ~ ... Cholesterol 7 alpha-hydroxylase. *Methane monooxygenase. *3A4. *Lanosterol 14 alpha-demethylase. *24-hydroxycholesterol 7α- ... Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid ... Tyrosine hydroxylase activity is increased in the short term by phosphorylation. The regulatory domain of tyrosine hydroxylase ...
Hydroxylation in the kidneys of calcifediol to calcitriol by 1-alpha-hydroxylase is tightly regulated: it is stimulated by ... The cholesterol undergoes a four-step process to make 7-dehydrocholesterol, the same compound that is produced in the skin of ... 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, a kidney enzyme that converts calcifediol to calcitriol. Coulston AM, Boushey C, ... Cholesterol is extracted from wool grease and wool wax alcohols obtained from the cleaning of wool after shearing. ...
... an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene". ... developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha ... an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene". ... LRH-1 plays a critical role in the regulation of development, cholesterol transport, bile acid homeostasis and steroidogenesis ...
X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase ... Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene (nuclear receptor ... "Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha". Proceedings of the National Academy of ... "PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ...
Payne AH, Hales DB (Dec 2004). "Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones". ... 25-Hydroxyvitamin D 1-alpha-hydroxylase (VD 1A hydroxylase) also known as cytochrome p450 27B1 (CYP27B1) or simply 1-alpha- ... 25-Hydroxyvitamin+D3+1-alpha-Hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH) Human CYP27B1 ... hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene. VD 1A hydroxylase is located in the ...
5 alpha-dihydrotestosterone and [3H]cortisol binding to plasma proteins". J. Steroid Biochem. 33 (2): 251-5. doi:10.1016/0022- ... Aminoglutethimide inhibits cholesterol side-chain cleavage enzyme, also known as P450scc or CYP11A1, which is responsible for ... also known as 17α-hydroxylase/17,20-lyase, which is responsible for the conversion of pregnane steroids into androgens, as well ... 952-. ISBN 978-1-60913-713-7.. *^ a b c d e f g h Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists ( ...
Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase ... The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin pigmentation. In secondary ... To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. ... Winqvist O, Karlsson FA, Kämpe O (June 1992). "21-Hydroxylase, a major autoantigen in idiopathic Addison's disease". The Lancet ...
Postorgasmic illness syndrome (POIS), through production of tyrosine hydroxylase and dopamine β-hydroxylase, which two enzymes ... The rapid actions of ACTH include stimulation of cholesterol delivery to the mitochondria where the P450scc enzyme is located. ... melanotropin alpha. melanocyte-stimulating hormone. α-MSH. 138-150 corticotropin-like intermediate peptide. CLIP. 156-176 ... P450scc catalyzes the first step of steroidogenesis that is cleavage of the side-chain of cholesterol. ACTH also stimulates ...
17 alpha-hydroxylase deficiency causes an inability to produce cortisol. Instead, extremely high levels of the precursor ... 11β-hydroxylase deficiency, aka apparent mineralocorticoid excess syndrome, involves a defect in the gene for 11β- ... "C-17 Hydroxylase Deficiency: Practice Essentials, Pathophysiology, Epidemiology". February 2018.. Cite journal requires , ... the JNC 7 report". JAMA. 289 (19): 2560-72. doi:10.1001/jama.289.19.2560. PMID 12748199.. ...
... and does not affect cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/17,20-lyase, 21-hydroxylase, or 11β- ... Chu YH, Li QA, Zhao ZF, Zhou YP, Cao DC (1985). "[Antiprogestational action of 5 alpha-dihydronorethisterone]". Zhongguo Yao Li ... GREENBLATT RB (1956). "The progestational activity of 17-alpha-ethinyl-19-nortestosterone". J. Clin. Endocrinol. Metab. 16 (7 ... hydroxylase.[51] Since it is not aromatized (and hence cannot be transformed into an estrogenic metabolite), unlike ...
Cholesterol side-chain cleavage enzyme. *Steroid 11-beta-hydroxylase. *Aldosterone synthase. *Frataxin ... These alpha helices compose approximately 75% of citrate synthase's tertiary structure, while the remaining residues mainly ... Citrate synthase's 437 amino acid residues are organized into two main subunits, each consisting of 20 alpha-helices. ... conversion begins with the negatively charged carboxylate side chain oxygen atom of Asp-375 deprotonating acetyl CoA's alpha ...
To assay conversion of cholesterol to pregnenolone, radiolabeled cholesterol has been used.[16] Pregnenolone product can be ... Pregnenolone can be converted to 17α-hydroxypregnenolone by the enzyme 17α-hydroxylase (CYP17A1). Using this pathway, termed Δ5 ... Pregnenolone is synthesized from cholesterol.[14] This conversion involves hydroxylation of the side chain at the C20 and C22 ... Hanukoglu I, Jefcoate CR (1980). "Pregnenolone separation from cholesterol using Sephadex LH-20 mini-columns". Journal of ...
... the inability of prolyl hydroxylases to catalyze reactions results in stabilization of hypoxia-inducible factor alpha, which is ... The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol. Cholesterol can, in turn, be used ... In the citric acid cycle all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate, ... 282 (7): 4524-32. doi:10.1074/jbc.M610415200. PMID 17182618.. *^ a b c d e Voet, Donald; Judith G. Voet; Charlotte W. Pratt ( ...
cholesterol 24-hydroxylase. 1 subfamily, 1 gene. CYP46A1 CYP51. cholesterol biosynthesis. 1 subfamily, 1 gene, 3 pseudogenes. ... steroid biosynthesis, 17-alpha hydroxylase. 1 subfamily, 1 gene. CYP17A1 CYP19. steroid biosynthesis: aromatase synthesizes ... steroid 20α-hydroxylase, steroid 22-hydroxylase, cholesterol side-chain scission). ... CYP27A1 (bile acid biosynthesis), CYP27B1 (vitamin D3 1-alpha hydroxylase, activates vitamin D3), CYP27C1 (unknown function) ...
Cholesterol side-chain cleavage enzyme. *Steroid 11-beta-hydroxylase. *Aldosterone synthase. *Frataxin ... The basic residue or cofactor deprotonates the alpha carbon, and FAD accepts the hydride from the beta carbon, oxidizing the ... The structure of these proteins consists of a complex bundle of five alpha-helices, which is composed of an up-down 3-helix ... 29 (7): 643. doi:10.1016/j.cropro.2010.02.019.. *^ Dubos T, Pasquali M, Pogoda F, Casanova A, Hoffmann L, Beyer M (January 2013 ...
Cholesterol side-chain cleavage enzyme. *Steroid 11-beta-hydroxylase. *Aldosterone synthase. *Frataxin ... Forty percent of the amino acids are arranged in an alpha helical and twelve percent are arranged in beta sheets. Docking of ... 33 (7): 588-91. PMID 16080802.. *. Inada J, Okuno E, Kimura M, Kido R (1984). "Intracellular localization and characterization ... Humans express one kynureninase enzyme that is encoded by the KYNU gene located on chromosome 2.[6][7] ...
Cholesterol side-chain cleavage enzyme. *Steroid 11-beta-hydroxylase. *Aldosterone synthase. *Frataxin ... NDUFA1 - NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa. *NDUFA2 - NADH dehydrogenase (ubiquinone) 1 alpha ... NDUFA4L2 - NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2. *NDUFA5 - NADH dehydrogenase (ubiquinone) 1 alpha ... NDUFA8 - NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 8, 19kDa. *NDUFA9 - NADH dehydrogenase (ubiquinone) 1 alpha ...
Shih, C. -H.; Chu, I. K.; Yip, W. K.; Lo, C. (2006). "Differential Expression of Two Flavonoid 3'-Hydroxylase cDNAs Involved in ... hydroxylase, seems to be expressed in pathogen-specific 3-deoxyanthocyanidin phytoalexins synthesis,[89] for example in Sorghum ... 64 (7): 939-48. doi:10.1094/Phyto-64-939.. *^ Brencic, Anja; Winans, Stephen C. (March 2005). "Detection of and Response to ... doi:10.1016/S0043-1354(00)00039-7.. *^ Erickson, M.; Miksche, G. E. (1974). "On the occurrence of lignin or polyphenols in some ...
Cholesterol can be synthesized de novo in the adrenal cortex. Yet, the major source of cholesterol appears to be cholesterol ... Zhou M, Gomez-Sanchez CE (July 1993). "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone ... Progesterone → (hydroxylation at C17) → 17-alpha-hydroxyprogesterone → (hydroxylation at C21) → 11-Deoxycortisol → ( ... The precursor of steroids synthesized in the adrenal cortex is cholesterol that is stored in vesicles. ...
Zuber MX, Simpson ER, Waterman MR (Dec 1986). "Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in ... The first step in the biosynthesis involves the oxidative cleavage of the side-chain of cholesterol by cholesterol side-chain ... It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites.[5] It exerts its ... Randall VA (Apr 1994). "Role of 5 alpha-reductase in health and disease". Baillière's Clinical Endocrinology and Metabolism. 8 ...
In contrast, granulosa cells lack 17α-hydroxylase and 17,20-lyase, whereas theca cells express these enzymes and 17β-HSD but ... by the synthesis of androstenedione from cholesterol. Androstenedione is a substance of weak androgenic activity which serves ... "DHEA metabolites activate estrogen receptors alpha and beta". Steroids. 78 (1): 15-25. doi:10.1016/j.steroids.2012.10.002. PMC ... 122 (1): 131-7. doi:10.1037/a0029524. PMC 3570621. PMID 22889242.. *^ a b Edler C, Lipson SF, Keel PK (January 2007). "Ovarian ...
In plants and microorganisms, isoleucine is biosynthesized from pyruvic acid and alpha-ketoglutarate. Enzymes involved in this ... Phenylalanine hydroxylase. *Tyrosine aminotransferase. *4-Hydroxyphenylpyruvate dioxygenase. *Homogentisate 1,2-dioxygenase. * ... 978-0-12-510604-7. .. *^ a b c d e f g h Shapiro BM, Stadtman ER (1970). "The Regulation of Glutamine Synthesis in ... 130 (7): 1835S-40S. doi:10.1093/jn/130.7.1835S. PMID 10867060.. *^ Manchester KL (1964). "Sites of Hormonal Regulation of ...
Cholesterol side-chain cleavage enzyme. *Steroid 11-beta-hydroxylase. *Aldosterone synthase. *Frataxin ... Branched-chain alpha-keto acid dehydrogenase complex. *3-hydroxy-2-methylbutyryl-CoA dehydrogenase ... Normal values at rest are usually between 60 and 174 IU/L,[7] where one unit is enzyme activity, more specifically the amount ... 7 (3): e32471. doi:10.1371/journal.pone.0032471. PMC 3306319. PMID 22438879.. ...
EC 6.2.1.28: 3-alpha,7-alpha-dihydroxy-5-beta-cholestanate--CoA ligase ... Phenylalanine hydroxylase EC 1.14.16.1. *Category:EC 1.14.18 *Tyrosinase EC 1.14.18.1 ... Cholesterol-5,6-oxide hydrolase. *Hepoxilin-epoxide hydrolase. *Isochorismatase. *Leukotriene-A4 hydrolase ... Category:EC 1.7.7 (with an iron-sulfur protein as acceptor). *Category:EC 1.7.99 (with other acceptors) *Nitrite reductase EC ...
The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol. Cholesterol can, in turn, be used ... In the citric acid cycle all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and ... This reaction is catalysed by prolyl 4-hydroxylases. Fumarate and succinate have been identified as potent inhibitors of prolyl ... ISBN 0-471-21495-7.. *^ a b c d e f g h i j k l m n o Stryer, Lubert (1995). "Citric acid cycle.". In: Biochemistry (Fourth ed ...
In macaques, alpha males have twice the level of serotonin released in the brain than subordinate males and females (as ... Hahn P (July 1984). "Effect of litter size on plasma cholesterol and insulin and some liver and adipose tissue enzymes in adult ... tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (DDC) and the coenzyme pyridoxal phosphate. The TPH-mediated ... "Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation". The ...
... can also be a side effect of alpha-1 blockers (alpha1 adrenergic blocking agents). Alpha1 blockers ... Another disease, dopamine beta hydroxylase deficiency, also thought to be underdiagnosed, causes loss of sympathetic ... There are numerous possible causes for orthostatic hypotension, such as certain medications (e.g. alpha blockers), autonomic ... 121 (7): 845-6. PMC 1704473. PMID 497968.. *^ Robertson D, Garland EM (September 2003). "Dopamine Beta-Hydroxylase Deficiency" ...
Davis RA, Miyake JH, Hui TY, Spann NJ (Apr 2002). "Regulation of cholesterol-7alpha-hydroxylase: BAREly missing a SHP". Journal ... Li T, Chanda D, Zhang Y, Choi HS, Chiang JY (Apr 2010). "Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription ... Li T, Chanda D, Zhang Y, Choi HS, Chiang JY (Apr 2010). "Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription ... Gbaguidi GF, Agellon LB (2004-01-01). "The inhibition of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter by ...
5 alpha-cholestan-3 beta, 6 alpha-diol; cholestan-3 beta, 5 alpha,6 beta-triol; 5-(25R)-cholesten-3 beta,26-diol, all at 50 ... Addition of cholesterol, delivered in beta-cyclodextrin, to squalestatin-treated cells restored cholesterol 7 alpha-hydroxylase ... Previous in vivo studies suggest that cholesterol may up-regulate cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in ... These experiments provide evidence that cholesterol rather than oxysterols regulate cholesterol 7 alpha-hydroxylase gene ...
... or alpha-) methylacyl-CoA racemase (AMACR) deficiency; cholesterol 7 alpha-hydroxylase (CYP7A1) deficiency. The most common ... sterol 27-hydroxylase (presenting as cerebrotendinous xanthomatosis, CTX) deficiency; 2- ( ... Cholic acid downregulates cholesterol-7-α-hydroxylase (rate-limiting step in bile acid synthesis), and cholesterol does the ... where it is synthesized from cholesterol. These two major bile acids are roughly equal in concentration in humans. Derivatives ...
CYP7A1, cholesterol 7 alpha-hydroxylase; HNF4, hepatocyte nuclear factor 4; IgM, immunoglobulin M; LDL-C, low-density ... lipoprotein cholesterol; MDR3, multidrug resistance protein 3; PPAR, peroxisome proliferator-activated receptor; PXR, pregnane ...
Tissue-Free Cholesterol. Free cholesterol concentration in the liver tissue was determined as described in our earlier studies ... This enzyme is the rate-limiting step in cholesterol conversion to bile acid, which is the principal pathway of cholesterol ... HDL particles serve as carriers of cholesterol from peripheral tissues to the liver. The HDL-mediated reverse cholesterol ... Moreover, despite elevation of serum cholesterol concentration and normality of HMG-CoA reductase, cholesterol concentration in ...
Control of steroidogenesis in rat corpus luteum: the rate of access of cholesterol to the active site of the cholesterol side- ... Action of gonadotrophic hormones on cholesterol side-chain cleavage and cholesterol ester hydrolase in the ovary of the ... The cholesterol-side-chain-cleavage enzyme complex in corpus luteum: kinetics of interaction of a lipid substrate with a ... Incorporation of cholesterol in vitro into rat liver microsomal fractions from serum and its effect on cytochrome P-450- ...
... these extracts may also inhibit carbohydrate metabolizing enzymes like alpha-amylase, alpha-glucosidase, and pancreatic lipase ... D. J. Peet, S. D. Turley, W. Ma et al., "Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear ... Freeze-dried bitter melon juice (1.5%) with diet normalized plasma TAG, cholesterol, and NEFA in female C57BL/6 mice fed a HF ... LXR also plays an important role in lipid and cholesterol metabolism. LXRα knockout mice develop enlarged fatty livers, ...
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 ... Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7alpha-hydroxylase (CYP7A1) is lost in Cyp8b1(-/-) ... Steroid 12-alpha-Hydroxylase / deficiency * Steroid 12-alpha-Hydroxylase / genetics * Transcription Factors / metabolism ...
Cholesterol 7a-hydroxylase (CYP7A) is the first and rate-limiting enzyme in bile acid synthesis pathway and is expressed only ... C. Juree, N. Kasem, B. William et al., "Induction of human cholesterol 7a-hydroxylase in HepG2 cells by 2, 4, 6 - ... Lack of CYP7A results in high levels of plasma cholesterol, whereas induction of CYP7A prevents elevation of blood cholesterol ... HMGCR activity directly affects the speed of cholesterol synthesis and the level of cholesterol [12]. Clinical results confirm ...
Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile ... Cholesterol 7-alpha-Hydroxylase / genetics, metabolism. Feedback, Physiological / drug effects. Fibroblast Growth Factors / ... Next Document: Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons.... ... Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the ...
Cholesterol 7 alpha-hydroxylase. Categories: Cell biology , Metabolic pathways , Fatty acids , Citric acid cycle , Cellular ...
... alpha}-hydroxylase gene transcription. Am J Physiol Gastrointest Liver Physiol. 2005;288(1):G74-G84.. 35. Li YC, Wang DP, ... PXR could inhibit cholesterol 7α-hydroxylase (CYP7A1) and inhibit bile acids biosynthesis.(33,34) CYP7A1 is a hepatic enzyme in ... Regulation of cholesterol 7 alpha-hydroxylase in the liver. Cloning, sequencing, and regulation of cholesterol 7 alpha- ... X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene ...
cholesterol. and septic (n = 20) (50/50. energy intake/energy No difference in energy expenditure or energy intake/ et al130 ( ... Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholester- The ideal emulsion would be one ... Cotter R. and cholesterol levels in serum of neo- matory lipid mediators: a new pharmacologic genus. trapping antioxidant ... incompat- cholesterol than those who received the 10% SOFE. a tetraenoic acid.63 Unfortunately.74 previously discussed. and the ...
... cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, ... Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of ...
Measurement of cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes, incubated with 1 microM-dexamethasone, ... As with bile acid synthesis from [14C]cholesterol, no change in enzyme activity was found in hepatocytes cultured in the ... Addition of inhibitors of protein and mRNA synthesis lowered bile acid production and cholesterol 7 alpha-hydroxylase activity ... We conclude that glucocorticoids regulate bile acid synthesis in rat hepatocytes by induction of enzyme activity of cholesterol ...
cholesterol Storage - glycogen, triglycerides, lipid soluble vitamins, Fe, Cu Catabolic - endogenous substances - hormones and ... higher in hepatitis B and C, hereditary haemochromatosis, alpha-1-antitrypsin deficiency ... cholesterol 7 alpha-hydroxylase: - vs ++ - bile formation:. -- bile-salt dependent: ++ vs -. -- non-bile-salt dependent: - vs ... bile formation and excretion into the gut - bilirubin, IgA, bile acids, cholesterol, elimination of environmental toxins, ...
Genomes and Genes about Experts and Doctors on steroid hydroxylases in Dallas, Texas, United States ... steroid 17 alpha hydroxylase*25 hydroxyvitamin d3 1 alpha hydroxylase*cytochrome p450 family 7*dietary cholesterol* ... We conclude that cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain ... Lund E, Guileyardo J, Russell D. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain ...
The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). An A to C ... Alpha tocopherol · Apolipoprotein E3 (Leidein) · Dgat1 protein, mouse · Diacylglycerol acyltransferase · Retinol · Animal ... Chemicals / CAS: cholesterol 7alpha monooxygenase, 9037-53-0; cholesterol, 57-88-5; lipid, 66455-18-3; Cholesterol 7-alpha- ... Cholesterol · Cholesterol 7alpha monooxygenase · Cholesterol ester · Cytochrome P450 isoenzyme · Messenger RNA · Sterol · ...
Health · Animal · Bile Acids and Salts · Cells, Cultured · Cholesterol 7-alpha-Hydroxylase · Culture Media · Liver · Male · ... Maintenance of bile acid synthesis and cholesterol 7α-hydroxylase activity in cultured rat hepatocytes article. 1990 ... Treated cells had a slightly higher content of free cholesterol than control cells; contents of other lipids were not ... Chemicals/CAS: Bile Acids and Salts; Cholesterol 7-alpha-Hydroxylase, EC 1.14.13.17; Culture Media ...
Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of ... B1F, B1F2, CPF, FTF, FTZ-F1, FTZ-F1beta, LRH-1, LRH1, hB1F-2, CYP7A promoter-binding factor, alpha-1-fetoprotein transcription ... factor, b1-binding factor, hepatocyte transcription factor which activates enhancer II of hepatitis B virus, fetoprotein-alpha ... 0.1M tris glycine with 10% glycerol and 0.01% thimerosal; pH 7. ...
del Castillo-Olivares, A. and Gil, G., Role of FXR and FTF in bile acid-mediated suppression of cholesterol 7alpha-hydroxylase ... Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha.Proc. Natl. Acad. Sci. U.S.A., 97, 12097- ... Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha.Cell, 93, 693-704 ( ... A novel liver X receptor agonist establishes species differences in the regulation of cholesterol 7alpha-hydroxylase (CYP7a). ...
The negative effects of bile acids and tumor necrosis factor-alpha on the transcription of cholesterol 7alpha-hydroxylase gene ... The pharmacological exploitation of cholesterol 7alpha-hydroxylase, the key enzyme in bile acid synthesis: from binding resins ... Insights in the regulation of cholesterol 7alpha-hydroxylase gene reveal a target for modulating bile acid synthesis. ... Suppression of bile acid synthesis, but not of hepatic cholesterol 7alpha-hydroxylase expression, by obstructive cholestasis in ...
HMGCR/HMG-CoA, hydroxymethylglutaryl-CoA reductase; CYP51, sterol 14 alpha-demethylase; CYP7A1, cholesterol 7 alpha-hydroxylase ... hydroxylase, a rate‑limiting enzyme of cholesterol catabolism, were increased. Moreover, the ethanol extract inhibited lipase ... total cholesterol, HDL cholesterol and LDL cholesterol) levels in C57BL/6J mice fed a high-fat diet. (A) Total cholesterol ... total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and free fatty acids] ...
... knockout mice develops spontaneous hypercholesterolemia but the detailed mechanisms by which EP4 affects cholesterol ... Deficiency of EP4 also increased de novo cholesterol synthesis and altered cholesterol fluxes in and out of the liver. Treating ... Activation of EP4 serves as an effective novel strategy to promote cholesterol disposal in the forms of bile acids in order to ... In summary, EP4 plays a critical role in maintaining cholesterol homeostasis by regulating the synthesis and elimination of ...
Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell1998;93 (5) : ... Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest2002;110 (1) :109- ... Disruption of cholesterol 7alpha-hydroxylase gene in mice. I. Postnatal lethality reversed by bile acid and vitamin ... Nuclear receptors in cholesterol catabolism: molecular biology of the enterohepatic circulation of bile salts and its role in ...
Effects of 3-methylcholanthrene and DDT on cholesterol 7 alpha-hydroxylase in rats. Durg-Nutr Interact 1(1):15-21, PMID: ... We defined abnormal lipids as elevated lipids (cholesterol, triglycerides, or fatty acids) in blood or liver, increased liver ... Abbreviations: CBA, conjugated bile acids; CHO, cholesterol; DPC, day post-coitus; F, females; FAs, fatty acids; GD, ... ratio of pollutant levels by the triglyceride and cholesterol content), b) include the blood lipid content as a covariate in ...
The abnormal buildup of cholesterol in the brain probably also contributes to the death of nerve cells. The loss of these cells ... In the brain, a decrease in enzyme activity results in an accumulation of cholesterol and alters neurosteroid production ... Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet. ... Oxysterol 7-alpha-hydroxylase helps maintain normal cholesterol levels in the brain and, by producing neurosteroids through ...
... genetic removal of Cyp7a1 promotes increased intestinal sterol synthesis and increases 12-alpha-hydroxylase (Cyp8b1) expression ... Cholesterol 7alpha-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders. J ... Transcription is promoted by interactions between cholesterol and the cholesterol-sensor liver X receptor alpha (LXRα) and is ... Down-regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression by bile acids in primary rat hepatocytes is mediated ...
Different hepatocytes express the cholesterol 7 alpha-hydroxylase gene during its circadian modulation in vivo ... Heterologous ferredoxin reductase and flavodoxin protect Cos-7 cells from oxidative stress ...
PCN treatment has been shown to enhance cholesterol turnover (Honohan and Parkinson, 1975), decrease cholesterol hydroxylase ... 1995) Effects of pregnenolone-16 alpha-carbonitrile on the metabolism of cholesterol in rat liver microsomes. Lipids 30:361-364 ... 1984) Modulation of the stimulatory effect of pregnenolone-16 alpha-carbonitrile on biliary cholesterol output in the rat by ... 1978) The suppressive effect of the catatoxic steroid, pregnenolone-16 alpha-carbonitrile, on liver microsomal cholesterol- ...
  • 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. (wikipedia.org)
  • The inhibition of cholesterol 7-alpha-hydroxylase (CYP7A1) represses bile acid biosynthesis. (wikipedia.org)
  • CYP7A1 is located in the endoplasmic reticulum (ER) and is important for the synthesis of bile acid and the regulation of cholesterol levels. (wikipedia.org)
  • These inflammatory cytokines, which include tumor necrosis factor alpha and interleukin-1beta, act upon the liver parenchymal cells causing a rapid repression of the CYP7A1 gene. (wikipedia.org)
  • CYP7A1 is upregulated by the nuclear receptor LXR (liver X receptor) when cholesterol (to be specific, oxysterol) levels are high. (wikipedia.org)
  • Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7alpha-hydroxylase (CYP7A1) is lost in Cyp8b1(-/-) mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. (nih.gov)
  • cholesterol 7 alpha-hydroxylase (CYP7A1) deficiency. (wikipedia.org)
  • Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. (biomedsearch.com)
  • Furthermore, rifampicin inhibits CYP7A1, a rate-limiting enzyme in the conversion of cholesterol into bile acids, and so reducing bile acids synthesis. (ispub.com)
  • The gene's product is an enzyme called cholesterol 7-alpha hydroxylase (CYP7A1), and it is essential for the normal elimination of cholesterol. (eurekalert.org)
  • EP4 deficiency negatively regulate bile acid synthesis through repression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK)-mediated cholesterol 7α-hydroxylase (CYP7A1) expression and that the hypercholesterolemia in EP4 knockout mice is due to a defect in cholesterol conversion into bile acids. (nih.gov)
  • Mice lacking PXR (PXR-KO) were used in the present study to delineate the role of PXR in regulating hepatomegaly and regulating the activity of CYP3A , organic anion transporting polypeptide-2 ( Oatp2 ), and Cyp7a1 (cholesterol 7α-hydroxylase) gene products in vivo. (aspetjournals.org)
  • Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. (abcam.com)
  • Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARα, liver X receptor alpha (LXRα), cholesterol 7α-hydroxylase (CYP7A1), and ATP binding cassette subfamily A member 1 (ABCA1) mRNA and protein expressions while decreased SREBP-1c and fatty acid synthase (FAS) mRNA, and protein expressions. (frontiersin.org)
  • This suggests that variation in the cholesterol 7alpha-hydroxylase gene (CYP7A1), a key enzyme in bile-acid biosynthesis, may influence the statin response. (cdc.gov)
  • Interactions between common genetic polymorphisms in ABCG5/G8 and CYP7A1 on LDL cholesterol-lowering response to atorvastatin. (cdc.gov)
  • Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. (olink.com)
  • In previous studies, we found that fibroblast growth factor receptor 4 (FGFR4) plays an important role in maintaining bile acid homeostasis by regulating the expression of cholesterol 7α-hydroxylase (CYP7A1), a rate-limiting enzyme for bile acid biosynthesis. (cdc.gov)
  • New studies indicate that genetic variation in cholesterol 7α-hydroxylase activity accounts for a significant fraction of the inter-individual variation in plasma LDL-cholesterol concentrations in the general population, and a specific CYP7A1 allele associated with increased plasma LDL-cholesterol concentrations has been identified. (elsevier.com)
  • Oxysterols: modulators of cholesterol metabolism and other processes. (semanticscholar.org)
  • The effect of taurine on cholesterol metabolism. (semanticscholar.org)
  • Together with the oxysterol receptors NR1H3 /LXR-alpha and NR1H2 /LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. (rcsb.org)
  • To this end, we explored the effect of CsA therapy on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the rate-limiting enzyme in cholesterol synthesis), LDL, and high-density lipoprotein (HDL) receptors (the critical factors in metabolism of the cholesterol-rich LDL and HDL particles), and of cholesterol 7α-hydroxylase, (the rate-limiting step in cholesterol catabolism to bile acids). (aspetjournals.org)
  • Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism. (semanticscholar.org)
  • Quan G, Xie C, Dietschy J, Turley S. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. (labome.org)
  • Hepatic cholesterol metabolism in normo- and hyperlipidemic patients with cholesterol gallstones. (wikipathways.org)
  • Heavy proteinuria is required to exhibit decreased LDL receptor gene expression in hepatocytes, and alter gene expression of 2 key enzymes for LDL and cholesterol homeostasis: Increased activity of HMG-CoA reductase, the rate limiting enzyme for cholesterol synthesis, and reduced activity of 7α-hydroxylase, the rate limiting enzyme for cholesterol metabolism and bile acid synthesis. (wikidoc.org)
  • Effects of Growth Hormone on Hepatic Cholesterol Metabolism. (patentgenius.com)
  • Paolo Parini et al, "Cholesterol and Lipoprotein Metabolism in Aging" Arterioscler Thromb Vasc Biol, Apr. (patentgenius.com)
  • The liver is the central organ in the metabolism of cholesterol and other fats. (stanford.edu)
  • To explore whether aging per se increases cholesterol saturation of bile and gallstone prevalence, and to investigate age-related changes in hepatic and biliary lipid metabolism, we studied gallstone-susceptible C57L mice and resistant AKR mice of both genders fed 8 weeks with a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butter fat starting at (young adult) 8, (older adult) 36, and (aged) 50-weeks-of-age. (elsevier.com)
  • Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. (cranberryinstitute.org)
  • Cohen, JC 1999, ' Contribution of cholesterol 7α-hydroxylase to the regulation of lipoprotein metabolism ', Current Opinion in Lipidology , vol. 10, no. 4, pp. 303-307. (elsevier.com)
  • The localization and characterization of the human 7α-hydroxylase gene, as well as the identification of polymorphisms, provide the molecular tools necessary to investigate the role of this gene in disorders of cholesterol and bile acid metabolism. (elsevier.com)
  • Liver cholesterol metabolism following trauma. (meta.org)
  • 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. (wikipedia.org)
  • Cholesterol 7 alpha-hydroxylase is the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7α-hydroxycholesterol. (wikipedia.org)
  • Disruption of the sterol 12alpha-hydroxylase gene (Cyp8b1) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. (nih.gov)
  • Cholic acid downregulates cholesterol-7-α-hydroxylase (rate-limiting step in bile acid synthesis), and cholesterol does the opposite. (wikipedia.org)
  • Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. (rcsb.org)
  • To investigate the biochemical background of these changes, the effects of insulin on bile acid synthesis and cholesterol 7α-hydroxylase and sterel 27-hydroxylase, two key enzymes in routing of cholesterol toward bile acids, were studied in cultured rat hepatocytes. (tudelft.nl)
  • The decrease of bile acid synthesis correlated well with the suppression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase activity. (tudelft.nl)
  • We conclude that physiological concentrations of insulin suppress bile acid synthesis by downregulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase gene transcription, and that this effect is mediated through a direct action of the hormone on the hepatocyte. (tudelft.nl)
  • We investigated the lobular localization and molecular level of expression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. (tudelft.nl)
  • Their synthesis in the liver provides a metabolic pathway for the catabolism of cholesterol and their detergent properties promote the solubilisation of essential nutrients and vitamins in the small intestine. (bmj.com)
  • However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. (springer.com)
  • Systemic cholesterol homeostasis is achieved by its synthesis and conversion to BAs in the liver as well as feedback mechanisms mediated by BAs. (springer.com)
  • 5′-AMP-activated protein kinase (AMPK) inactivates critial ensymes in fatty acid and cholesterol synthesis. (bmj.com)
  • 5 HMG-CoA reductase is the rate-limiting enzyme of cholesterol synthesis. (bmj.com)
  • To study the effect of steroid hormones on bile acid synthesis by cultured rat hepatocytes, cells were incubated with various amounts of these compounds during 72 h and conversion of [4-14C]cholesterol into bile acids was measured. (biochemj.org)
  • Dexamethasone proved to be the most efficacious inducer, giving 3-fold and 7-fold increases in bile acid synthesis during the second and third 24 h incubation periods respectively, at a concentration of 50 nM. (biochemj.org)
  • As with bile acid synthesis from [14C]cholesterol, no change in enzyme activity was found in hepatocytes cultured in the presence of 10 microM steroid hormones other than glucocorticoids. (biochemj.org)
  • Addition of inhibitors of protein and mRNA synthesis lowered bile acid production and cholesterol 7 alpha-hydroxylase activity and prevented the rise of both parameters with dexamethasone, suggesting regulation at the mRNA level. (biochemj.org)
  • We conclude that glucocorticoids regulate bile acid synthesis in rat hepatocytes by induction of enzyme activity of cholesterol 7 alpha-hydroxylase. (biochemj.org)
  • In the adult, however, synthesis exceeds the need for structural cholesterol so that there is a constant excretion of sterol from the CNS into the plasma at a rate of about 0.023 mg/day. (labome.org)
  • Furthermore, mice fed aronia compounds demonstrated a suppressed hepatic mRNA expression of stearoyl‑CoA desaturase 1, which promotes fatty acid synthesis, whereas the expression levels of cholesterol 7 alpha‑hydroxylase, a rate‑limiting enzyme of cholesterol catabolism, were increased. (spandidos-publications.com)
  • We sought to determine the cause of hypercholesterolemia in EP4 knockout mice, focusing on the role of EP4 in regulating the synthesis and elimination of cholesterol. (nih.gov)
  • Deficiency of EP4 also increased de novo cholesterol synthesis and altered cholesterol fluxes in and out of the liver. (nih.gov)
  • In summary, EP4 plays a critical role in maintaining cholesterol homeostasis by regulating the synthesis and elimination of bile acids. (nih.gov)
  • [11] Specifically, patients on peritoneal dialysis generally have higher LDL and total cholesterol due to the considerable protein loss into the peritoneal dialysate that stimulates hepatic protein synthesis, including LDL and other lipoproteins . (wikidoc.org)
  • Kurt Einarsson et al, "Bile Acid Synthesis in Man: Assay of Hepatic Microsomal Cholesterol 7.alpha. (patentgenius.com)
  • To conclude, baked cod fillet intake resulted in lower serum cholesterol, which was probably caused by lower endogenous cholesterol synthesis, and higher n -3 PUFA in serum and tissues in obese Zucker fa/fa rats. (mdpi.com)
  • Bile-acid biosynthesis is a key determinant of intracellular cholesterol and, in turn, cholesterol synthesis rate in hepatocytes. (cdc.gov)
  • Increasing age augmented biliary secretion and intestinal absorption of cholesterol, reduced hepatic synthesis and biliary secretion of bile salts, and decreased gallbladder contractility, all of which increased susceptibility to cholesterol cholelithiasis in C57L mice. (elsevier.com)
  • Clinical studies have clearly established a relationship between bile acid synthesis and plasma LDL-cholesterol concentrations. (elsevier.com)
  • Interruption of the enterohepatic circulation of bile acids leads to increased bile acid synthesis and a reduction in plasma LDL-cholesterol concentrations. (elsevier.com)
  • Cholesterol 7α-hydroxylase (7α-hydroxylase) is a microsomal cytochrome P450 that catalyzes the first step in bile acid synthesis. (elsevier.com)
  • downregulating the gene expression and activity of enzymes including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and sterol-responsive element binding protein-2 (SREBP2) and upregulating the low-density lipoprotein receptor (LDLR) to reduce the denovo synthesis of cholesterol. (foodandnutritionresearch.net)
  • Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. (rcsb.org)
  • To study the mechanism of suppression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase activity, the effects of insulin on their respective levels of messenger RNA (mRNA) and gene transcription were assessed. (tudelft.nl)
  • Transient expression experiments using a construct containing the proximal 348 basepairs of the cholesterol 7α-hydroxylase promoter fused to the chloramphenicol acetyltransferase (CAT) gene (-348Rcat) showed a significant reduction of transcriptional activity (-64%) with insulin, indicating that a sequence important for an insulin-induced transcriptional response is located within the first 348 basepairs, preceding the transcription start of the cholesterol 7α-hydroxylase promoter. (tudelft.nl)
  • Enzyme activity, mRNA, and gene transcription of cholesterol 7α-hydroxylase were predominant in pericentral hepatocytes of control rats, being 7.9-, 9.9-, and 4.4-fold higher than in periportal hepatocytes, respectively. (tudelft.nl)
  • Similar localization was found for sterol 27-hydroxylase: 2.9-, 2.5-, and 1.7-fold higher enzyme activity, mRNA, and gene transcription, respectively, was found in pericentral hepatocytes. (tudelft.nl)
  • CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. (springer.com)
  • This gene provides instructions for making an enzyme called oxysterol 7-alpha-hydroxylase. (medlineplus.gov)
  • CYP7B1 gene mutations that cause spastic paraplegia type 5A reduce or eliminate the activity of oxysterol 7-alpha-hydroxylase. (medlineplus.gov)
  • They studied the family of one patient and found that carriers of mutations in the gene did indeed have elevated cholesterol, including three siblings with dangerously elevated levels. (eurekalert.org)
  • By understanding the mechanism - how this gene affects cholesterol regulation- we can diagnose those at risk earlier and choose better treatments for them. (eurekalert.org)
  • The discovery is the fifth gene known to cause elevated cholesterol when it is defective. (eurekalert.org)
  • The researchers hypothesized that a mutation that knocked out this gene would lead to an accumulation of cholesterol in the liver as the primary route of converting cholesterol to bile acids is blocked. (eurekalert.org)
  • Even family members with a mutation in just one of the two copies of the gene had significantly elevated cholesterol levels, the scientists found, equivalent to a heart attack risk more than 50 percent higher than average. (eurekalert.org)
  • Taking into account that the original DNA sample was drawn from patients with cholesterol problems, the team was able to estimate that several hundred thousand people in the U.S. and Europe will be affected by defects in this gene. (eurekalert.org)
  • Yanase T, Sanders D, Shibata A, Matsui N, Simpson E, Waterman M. Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a 7-basepair duplication in the N-terminal region of the cytochrome P45017 alpha (CYP17) gene. (labome.org)
  • Lund E, Xie C, Kotti T, Turley S, Dietschy J, Russell D. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. (labome.org)
  • David K. Spady et al, "Adenovirus-mediated Transfer of a Gene Encoding Cholesterol 7.alpha. (patentgenius.com)
  • Interestingly, targeted inactivation of the gene encoding cholesterol 7α-hydroxylase does not lead to increased plasma LDL-cholesterol concentrations in mice. (elsevier.com)
  • In this paper, we describe the cloning, characterization, and chromosomal mapping of the human 7α-hydroxylase gene (CYP7). (elsevier.com)
  • Orphan receptors chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and retinoid X receptor (RXR) activate and bind the rat cholesterol 7alpha-hydroxylase gene (CYP7A). (omeka.net)
  • The cholesterol 7alpha-hydroxylase gene (CYP7A) is transcriptionally regulated by a number of factors, including hormones, bile acids, and diurnal rhythm. (omeka.net)
  • Both medium and high dose of PMR showed significant alterations in TC, which were related to the downregulation effects on hydroxyl methyl-glutaryl coenzyme A reductase (HMGCR) and upregulation effects on cholesterol 7-alpha-hydroxylase or cytochrome P450 7A (CYP7A). (hindawi.com)
  • Thus, hepatic expressions of cholesterol 7α-hydroxylase (the rate-limiting step in cholesterol conversion to bile acids), LDL receptor, and high-density lipoprotein (HDL) receptor proteins, as well as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were determined in rats treated with CsA (18 mg/kg/day) or placebo for 3 weeks. (aspetjournals.org)
  • Effects of cholestyramine on cholesterol balance parameters and hepatic HMG-CoA reductase and cholesterol-7-alpha-hydroxylase activities in swine. (semanticscholar.org)
  • For use, alone or in combination with an HMG-CoA reductase inhibitor, as adjunctive therapy to diet and exercise for the reduction of elevated LDL cholesterol in patients with primary hypercholesterolemia (Fredrickson Type IIa). (drugbank.ca)
  • Consuming Baked Cod Diet resulted in lower serum cholesterol and lower hepatic mRNA concentrations of HMG-CoA reductase and sterol O-acyltransferase-2 without affecting serum bile acid concentration, faecal excretion of cholesterol and bile acid, and hepatic concentrations of bile acids, cholesterol and cholesterol 7 alpha-hydroxylase mRNA when compared to Control Diet. (mdpi.com)
  • Cholesterol supersaturation of bile appears to be a prerequisite for gallstone formation, which involves a variety of factors that affect the activity of low-density lipoprotein (LDL) uptake, hepatic 3-methylglutaryl coenzyme A reductase (HMG CoA), acyl cholesterol-lecithin acyltransferase, and 7-alpha hydroxylase. (medscape.com)
  • Measurements of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activities were correlated with steady state messenger RNA levels and related to cholesterol 7α-hydroxylase activities in the sitosterolemic homozygotes and nine controls. (elsevier.com)
  • These results demonstrate that high-tissue sitosterol concentrations do not inhibit hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity or steady state messenger RNA levels and that they competitively block cholesterol 7α-hydroxylase activity and raise plasma cholesterol levels. (elsevier.com)
  • After the 8-week feeding, gallstone prevalence, gallbladder size, biliary lipid secretion rate, and HMG-CoA reductase activity were significantly greater but cholesterol 7α-hydroxylase activity was lower in C57L mice of both genders compared with AKR mice. (elsevier.com)
  • Previous in vivo studies suggest that cholesterol may up-regulate cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, but these studies are open to question as they were carried out in whole animals. (semanticscholar.org)
  • Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. (springer.com)
  • 6 AMPK activity therefore inhibits fatty acid and cholesterol biosynthesis and promotes fatty acid oxidation, thereby opposing intracellular lipid accumulation and development of insulin resistance in non-adipose tissues. (bmj.com)
  • Regulation of cholesterol 7 alpha-hydroxylase expression by sterols in primary rat hepatocyte cultures. (semanticscholar.org)
  • The importance of cholesterol and 'oxysterols' in the regulation of cholesterol 7 alpha-hydroxylase is not clear. (semanticscholar.org)
  • In vitro regulation of bovine adrenal cortical acyl-CoA: cholesterol acyltransferase and comparison with the rat liver enzyme. (nih.gov)
  • Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. (nih.gov)
  • This was associated with a marked down-regulation of cholesterol 7α-hydroxylase in the liver and a severe reduction of lipoprotein lipase abundance in skeletal muscle and adipose tissue. (aspetjournals.org)
  • In conclusion, CsA administration for 3 weeks resulted in a significant reduction of hepatic cholesterol 7α-hydroxylase and marked down-regulation of skeletal muscle and adipose tissue lipoprotein lipase abundance in rats. (aspetjournals.org)
  • Here we review the genetics of familial cholestasis disorders, the functions of the affected genes in bile flow, and their regulation by bile acids and cholesterol. (bmj.com)
  • Although many roles have been described for BAs with regard to cholesterol homeostasis and endocrine signaling in both hepatic and extrahepatic tissues, we focus this review on conversion of cholesterol to BAs and sexual dimorphisms in the activity and regulation of enzymes involved in this process. (springer.com)
  • They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. (hmdb.ca)
  • Regulation of cholesterol 7 alpha-hydroxylase in the liver. (omeka.net)
  • Cloning, sequencing, and regulation of cholesterol 7 alpha-hydroxylase mRNA. (omeka.net)
  • [7] These sterols localize to the plasma membrane of cells, where they play an important structural role in the regulation of membrane fluidity and permeability and also influence the activity of enzymes, ion channels, and other cell components that are embedded within. (wikipedia.org)
  • We investigated hepatic cholesterol homeostasis in four homozygous sitosterolemic subjects from two unrelated families who showed enhanced absorption, diminished removal and increased tissue and plasma concentrations of sitosterol (24-ethyl cholesterol). (elsevier.com)
  • However, hepatic cholesterol 7α-hydroxylase activity was inhibited 30% in both the sitosterolemic homozygotes and rats with high liver sitosterol concentrations. (elsevier.com)
  • Sterol 27- hydroxylase activity was inhibited up to -58% after 24 hours of incubation with 140 nmol/L insulin. (tudelft.nl)
  • The decrease in enzyme activities could be explained by a concomitant reduction in the cholesterol 7α-hydroxylase (-76%) and sterol 27-hydroxylase (-62%) mRNA level. (tudelft.nl)
  • Transcriptional activity, as assessed by nuclear runoff assays, was decreased to the same extent, i.e., -60% for cholesterol 7α-hydroxylase and -75% for sterol 27-hydroxylase. (tudelft.nl)
  • Characterization of human sterol 27-hydroxylase. (wikipathways.org)
  • Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis. (semanticscholar.org)
  • Cholic acid, also known as 3α,7α,12α-trihydroxy-5β-cholan-24-oic acid is a primary bile acid that is insoluble in water (soluble in alcohol and acetic acid), it is a white crystalline substance. (wikipedia.org)
  • Cholic acid, along with chenodeoxycholic acid, is one of the two major bile acids produced by the liver, where it is synthesized from cholesterol. (wikipedia.org)
  • Cholic acid and chenocholic acid are primary bile acids synthesized in liver from cholesterol while deoxycholic acid and lithocholic acid are secondary bile acid formed in the intestine by the bacterial 7α-dehydroxylation of cholic acid and chenocholic acid and absorbed into blood for enterohepatic circulation. (ispub.com)
  • In NAFLD pathogenic process, the accumulation of lipid within the liver, especially total cholesterol (TC) and triglycerides (TG) accumulation, has been confirmed by dynamics research. (hindawi.com)
  • Kurt Einarsson et al, "Studies on Acyl-Coenzyme A: Cholesterol Acyltransferase Activity in Human Liver Microsomes", Journal of Lipid Research, 1989, vol. 30, pp. 739-746. (patentgenius.com)
  • The present article will review the latest updates on lipid management with emphases on the different classes of cholesterol-lowering agents and their clinical uses. (springer.com)
  • Karalis DG, Victor B, Ahedor L, Liu L. Use of lipid-lowering medications and the likelihood of achieving optimal LDL-cholesterol goals in coronary artery disease patients. (springer.com)
  • Wang, DQH 2002, ' Aging per se is an independent risk factor for cholesterol gallstone formation in gallstone susceptible mice ', Journal of Lipid Research , vol. 43, no. 11, pp. 1950-1959. (elsevier.com)
  • Monospecific antibody against purified rat liver cholesterol 7 alpha-hydroxylase cytochrome P-450 was used to screen a lambda gt11 cDNA library constructed from immuno-enriched polysomal RNA of cholestyramine-treated female rat liver. (omeka.net)
  • Our finding adds to the roster of genes that can cause a disorder of cholesterol in the blood and increase the risk of heart disease and stroke," Kane said. (eurekalert.org)
  • 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, we identified three loci affecting HDL-cholesterol levels in a screen for ENU-induced mutations in mice and discovered two mutated genes. (biomedcentral.com)
  • The former abnormality can contribute to hypercholesterolemia by limiting cholesterol catabolism, whereas the latter may contribute to hypertriglyceridemia and VLDL accumulation by limiting triglyceride-rich lipoprotein clearance in CsA-treated animals. (aspetjournals.org)
  • A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential. (springer.com)
  • FXR functions as the chief sensor of intracellular levels of bile acids (the end products of cholesterol catabolism) and the main executor of bile acid-induced transcriptional programmes. (physiology.org)
  • Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. (hmdb.ca)
  • Similarly, decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. (drugbank.ca)
  • 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)
  • Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. (springer.com)
  • RCT is a physiological process in which excess peripheral cholesterol is transported by high-density lipoprotein (HDL) or non-HDL to the liver for excretion into the bile and feces. (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 expression of key proteins involved in bile flow is tightly regulated by transcription factors of the nuclear hormone receptor family, which function as sensors of bile acids and cholesterol. (bmj.com)
  • Prostaglandin E receptor subtype 4 (EP4) knockout mice develops spontaneous hypercholesterolemia but the detailed mechanisms by which EP4 affects cholesterol homeostasis remains unexplored. (nih.gov)
  • Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. (springer.com)
  • Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. (springer.com)
  • Arteries and xanthomas in patients with sitosterolemia contain increased amounts of these sterols, particularly sitosterol, stigmasterol, campesterol, and their 5-alpha derivatives. (medscape.com)
  • Serum lipids, plant sterols, and cholesterol kinetic responses to plant sterol supplementation in phytosterolemia heterozygotes and control individuals. (medscape.com)
  • what happens to plant sterols and excess cholesterol upon entering enterocytes? (brainscape.com)
  • The demethylated products of the CYP51 reaction are vital intermediates in pathways leading to the formation of cholesterol in humans, ergosterol in fungi, and other types of sterols in plants. (wikipedia.org)
  • In the brain, oxysterol 7-alpha-hydroxylase is involved in a pathway that converts cholesterol to hormones called neurosteroids. (medlineplus.gov)
  • Oxysterol 7-alpha-hydroxylase helps maintain normal cholesterol levels in the brain and, by producing neurosteroids through altering existing hormones within the pathway, regulates the effects of neurosteroids on the brain. (medlineplus.gov)
  • In the brain, a decrease in enzyme activity results in an accumulation of cholesterol and alters neurosteroid production triggered by oxysterol 7-alpha-hydroxylase. (medlineplus.gov)
  • Polymorphisms of CYP46 or apo E do not explain levels of oxysterol or non-HDL cholesterol or the responsiveness to statin treatment in this study. (labome.org)
  • Guorong Xu et al, "Unexpected Inhibition of Cholesterol 7.alpha. (patentgenius.com)
  • The effect of this upregulation is to increase the production of bile acids and reduce the level of cholesterol in hepatocytes. (wikipedia.org)
  • The enzyme activity for cholesterol 7α-hydroxylase, examined in more detail, was dose dependently diminished on incubation of hepatocytes with various concentrations of insulin, reaching maximal reduction at 14 nmol/L of insulin. (tudelft.nl)
  • Measurement of cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes, incubated with 1 microM-dexamethasone, showed 10-fold and 90-fold increases after 48 and 72 h respectively, as compared with control cells. (biochemj.org)
  • Lessons From Studies in Rats and Humans", Growth Hormone & IGF Research,vol. 9, No. 1-7, pp. 1-7 (1999). (patentgenius.com)
  • Conversion of [4-14C]7 alpha-hydroxycholesterol, an intermediate of the bile acid pathway, to bile acids was not affected by dexamethasone. (biochemj.org)
  • We conclude that cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain. (labome.org)
  • We conclude that cholesterol turnover in brain activates the mevalonate pathway and that a constant production of geranylgeraniol in a small subset of neurons is required for LTP and learning. (labome.org)
  • The primary loop is comprised of the positive transcriptional regulators BMAL1 and CLOCK and the transcriptional repressors PERIOD (PER) and CRYPTOCHROME (CRY) [5] - [7] . (prolekare.cz)
  • Triglycerides, like LDL cholesterol, are major risk factors in atherosclerosis and other arterial disease. (eurekalert.org)
  • Research suggests that taking turmeric extract by mouth twice daily for 3 months reduces total cholesterol, low-density lipoprotein (LDL or "bad") cholesterol, and triglycerides in overweight people with high cholesterol. (webmd.com)
  • Following a 26‑day trial, serum triglycerides, free fatty acids and low‑density lipoprotein cholesterol levels were significantly lower in mice fed aronia juice residue or its ethanol extract than in the high‑fat‑fed control mice. (spandidos-publications.com)
  • These findings reveal the microsomal localization of 24-hydroxylase and provide subcellular insight into cholesterol turnover in the brain. (labome.org)
  • CsA-treated animals showed mild but significant elevations of plasma cholesterol and triglyceride concentrations. (aspetjournals.org)
  • reported a significant elevation of serum cholesterol and triglyceride concentrations in their transplant recipients treated with CsA, compared with the non-CsA-treated group. (aspetjournals.org)
  • Plasma cholesterol concentrations increased 120% in the sitosterolinfused rats and 29% in the untreated human homozygotes. (elsevier.com)
  • We investigated the cholesterol-lowering effect and potential mechanisms of chitooligosaccharide capsules (COSTC) in male SD rats fed a high-fat diet. (foodandnutritionresearch.net)
  • It facilitates fat absorption and cholesterol excretion. (hmdb.ca)
  • Ramirez D, Andersson S, Russell D. Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain. (labome.org)
  • We identified 19 in vivo studies and 7 in vitro studies that supported the biological plausibility of the obesogenic effects of p,p′ -DDT and p,p′ -DDE. (nih.gov)
  • In distinction, elevated hepatic sitosterol concentrations increase plasma cholesterol levels by competitively suppressing cholesterol 7α-hydroxylase activity. (elsevier.com)
  • Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. (cranberryinstitute.org)
  • Studies in which cholesterol 7α-hydroxylase was transiently overexpressed in hamsters and mice indicate that direct manipulation of cholesterol 7α-hydroxylase leads to changes in plasma LDL-cholesterol concentrations. (elsevier.com)
  • Insulin strongly reduced the rise in cholesterol 7α-hydroxylase activity induced by incubation with dexamethasone. (tudelft.nl)
  • Clinical studies have demonstrated that elevated levels of total cholesterol (total-C), LDL-C, and apolipoprotein B (Apo B, a protein associated with LDL-C) are associated with an increased risk of atherosclerosis in humans. (drugbank.ca)
  • The second line of mice which had very high levels of plasma total cholesterol and HDL-C was mapped to a missense mutation in CCAAT/enhancer binding protein α ( C/ebpα ). (biomedcentral.com)
  • The enzyme initiates the primary conversion of cholesterol into bile acids in the liver. (eurekalert.org)
  • The liver responds to excessive cholesterol by reducing the amount of receptors available to take up low density lipoprotein, or LDL, -- the "bad" cholesterol - from the blood. (eurekalert.org)
  • It is downregulated by sterol regulatory element-binding proteins (SREBP) when plasma cholesterol levels are low. (wikipedia.org)
  • A team lead by UCSF medical researchers has discovered a new disorder that can cause severely elevated blood cholesterol levels and may affect several hundred thousand people in the U.S. and Europe to varying degrees. (eurekalert.org)
  • Discovery of the disorder started from a deduction: Researchers knew the gene's function, so they hypothesized how mutations would affect cholesterol levels, vulnerability to gallstones and other factors. (eurekalert.org)
  • The scientists also predicted the presence of gallstones because inadequate bile acid levels would allow the cholesterol to crystallize into gallstones. (eurekalert.org)
  • Their cholesterol levels were above 300 mg/dl -- nearly double their family's average, putting them at extreme risk for coronary heart disease. (eurekalert.org)
  • Restraint of cholesterol accumulation in tissue pools associated with drastic short-term lowering of serum cholesterol levels by clofibrate or cholestyramine in hypercholesterolemic swine. (semanticscholar.org)
  • High levels of cholesterol or other fats (lipids) in the blood (hyperlipidemia). (webmd.com)
  • The effects of turmeric on cholesterol levels are conflicting. (webmd.com)
  • Activation of EP4 serves as an effective novel strategy to promote cholesterol disposal in the forms of bile acids in order to lower plasma cholesterol levels. (nih.gov)
  • [ 1 , 2 ] The original report detailed 2 sisters who presented with extensive tendon xanthomas but normal plasma cholesterol levels. (medscape.com)
  • With treatment, cholesterol levels can normalize, and xanthomas can completely regress. (medscape.com)
  • A clue to sitosterolemia diagnosis in a patient with highly elevated plasma cholesterol level is parents with normal cholesterol levels. (medscape.com)
  • Serena Tonstad et al, "The Effect of Growth Hormone on Low-Density Lipoprotein Cholesterol and Lipoprotein (a) Levels in Familial Hypercholesterolemia", vol. 45, No. 11, pp. 1415-1421 (1996). (patentgenius.com)
  • Despite the clinical long-term and near-term benefits of lowering cholesterol in, respectively, primary and secondary prevention of ASCVD, cholesterol levels remain under-treated, with many patients not achieving their recommended targets. (springer.com)
  • Specifically, the amount of saturated fats consumed has a great influence on blood cholesterol levels. (progressivehealth.com)
  • Besides saturated fats, trans fats can also raise blood cholesterol levels. (progressivehealth.com)
  • Trans fats are especially bad for blood cholesterol levels. (progressivehealth.com)
  • Inherited forms of hypercholesterolemia are present with very high circulating cholesterol levels. (biomedcentral.com)
  • Effect of phenobarbital on the conversion of cholesterol to taurocholic acid. (meta.org)
  • For patient education resources, see Digestive Disorders Center and Cholesterol Center , as well as Gallstones , Primary Biliary Cirrhosis (PBC) , Cirrhosis (Liver, Symptoms, Stages, and Diet) , and Primary Sclerosing Cholangitis . (medscape.com)
  • Cholesterol gallstones occur rarely in childhood and adolescence and increase linearly with age in both genders. (elsevier.com)