Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Salts: Substances produced from the reaction between acids and bases; compounds consisting of a metal (positive) and nonmetal (negative) radical. (Grant & Hackh's Chemical Dictionary, 5th ed)Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.Bile Ducts: The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.Cholic Acids: The 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholanic acid family of bile acids in man, usually conjugated with glycine or taurine. They act as detergents to solubilize fats for intestinal absorption, are reabsorbed by the small intestine, and are used as cholagogues and choleretics.Taurocholic Acid: The product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic.Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion.Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Cholesterol 7-alpha-Hydroxylase: A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS.Organic Anion Transporters, Sodium-Dependent: A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is driven either directly or indirectly by a gradient of sodium ions.Glycocholic Acid: The glycine conjugate of CHOLIC ACID. It acts as a detergent to solubilize fats for absorption and is itself absorbed.Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines (INTESTINAL REABSORPTION) into portal circulation, passage back into liver, and re-excretion in bile.Bile Canaliculi: Minute intercellular channels that occur between liver cells and carry bile towards interlobar bile ducts. Also called bile capillaries.Taurochenodeoxycholic Acid: A bile salt formed in the liver by conjugation of chenodeoxycholate with taurine, usually as the sodium salt. It acts as detergent to solubilize fats in the small intestine and is itself absorbed. It is used as a cholagogue and choleretic.Taurodeoxycholic Acid: A bile salt formed in the liver by conjugation of deoxycholate with taurine, usually as the sodium salt. It is used as a cholagogue and choleretic, also industrially as a fat emulsifier.Common Bile Duct: The largest bile duct. It is formed by the junction of the CYSTIC DUCT and the COMMON HEPATIC DUCT.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Gallbladder: A storage reservoir for BILE secretion. Gallbladder allows the delivery of bile acids at a high concentration and in a controlled manner, via the CYSTIC DUCT to the DUODENUM, for degradation of dietary lipid.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Cholestyramine Resin: A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium Cl(-) anion.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Hydroxysteroid Dehydrogenases: Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-.Cholagogues and Choleretics: Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Cholelithiasis: Presence or formation of GALLSTONES in the BILIARY TRACT, usually in the gallbladder (CHOLECYSTOLITHIASIS) or the common bile duct (CHOLEDOCHOLITHIASIS).Bile Duct Diseases: Diseases in any part of the ductal system of the BILIARY TRACT from the smallest BILE CANALICULI to the largest COMMON BILE DUCT.Bile Ducts, Intrahepatic: Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct.Bile Reflux: Retrograde bile flow. Reflux of bile can be from the duodenum to the stomach (DUODENOGASTRIC REFLUX); to the esophagus (GASTROESOPHAGEAL REFLUX); or to the PANCREAS.Bile Pigments: Linear TETRAPYRROLES that give a characteristic color to BILE including: BILIRUBIN; BILIVERDIN; and bilicyanin.Taurine: A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids.Cholestanetriol 26-Monooxygenase: An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.Symporters: Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Bile Duct Neoplasms: Tumors or cancer of the BILE DUCTS.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Glycochenodeoxycholic Acid: A bile salt formed in the liver from chenodeoxycholate and glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is a cholagogue and choleretic.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Steroid 12-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Taurolithocholic Acid: A bile salt formed in the liver from lithocholic acid conjugation with taurine, usually as the sodium salt. It solubilizes fats for absorption and is itself absorbed. It is a cholagogue and choleretic.Bile Ducts, Extrahepatic: Passages external to the liver for the conveyance of bile. These include the COMMON BILE DUCT and the common hepatic duct (HEPATIC DUCT, COMMON).Cholestanols: Cholestanes substituted in any position with one or more hydroxy groups. They are found in feces and bile. In contrast to bile acids and salts, they are not reabsorbed.Cholestasis, Intrahepatic: Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Chromatography, Gas: Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.Cholestanes: Derivatives of the saturated steroid cholestane with methyl groups at C-18 and C-19 and an iso-octyl side chain at C-17.Biliary Tract: The BILE DUCTS and the GALLBLADDER.Sodium Chloride: A ubiquitous sodium salt that is commonly used to season food.Sterols: Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)Biliary Fistula: Abnormal passage in any organ of the biliary tract or between biliary organs and other organs.CholanesGas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter.Cholecystectomy: Surgical removal of the GALLBLADDER.Cholestenones: CHOLESTENES with one or more double bonds and substituted by any number of keto groups.Glycodeoxycholic Acid: A bile salt formed in the liver by conjugation of deoxycholate with glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and choleretic.Eubacterium: A genus of gram-positive, rod-shaped bacteria found in cavities of man and animals, animal and plant products, infections of soft tissue, and soil. Some species may be pathogenic. No endospores are produced. The genus Eubacterium should not be confused with EUBACTERIA, one of the three domains of life.Bilirubin: A bile pigment that is a degradation product of HEME.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Malabsorption Syndromes: General term for a group of MALNUTRITION syndromes caused by failure of normal INTESTINAL ABSORPTION of nutrients.Cholesterol, Dietary: Cholesterol present in food, especially in animal products.Gallstones: Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Cholates: Salts and esters of CHOLIC ACID.Selenium Radioisotopes: Unstable isotopes of selenium that decay or disintegrate emitting radiation. Se atoms with atomic weights 70-73, 75, 79, 81, and 83-85 are radioactive selenium isotopes.Sodium Chloride, Dietary: Sodium chloride used in foods.Duodenum: The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Salt Gland: A compound tubular gland, located around the eyes and nasal passages in marine animals and birds, the physiology of which figures in water-electrolyte balance. The Pekin duck serves as a common research animal in salt gland studies. A rectal gland or rectal salt gland in the dogfish shark is attached at the junction of the intestine and cloaca and aids the kidneys in removing excess salts from the blood. (Storer, Usinger, Stebbins & Nybakken: General Zoology, 6th ed, p658)Xanthomatosis: A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.Allylamine: Possesses an unusual and selective cytotoxicity for VASCULAR SMOOTH MUSCLE cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation.Cholenes: Unsaturated derivatives of cholane with methyl groups at C-10 and C-13 and a branched five-carbon chain at C-17. They must have at least one double bond in the ring system.Dehydrocholic Acid: A semisynthetic bile acid made from cholic acid. It is used as a cholagogue, hydrocholeretic, diuretic, and as a diagnostic aid.Common Bile Duct Diseases: Diseases of the COMMON BILE DUCT including the AMPULLA OF VATER and the SPHINCTER OF ODDI.Kinetics: The rate dynamics in chemical or physical systems.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)3-Hydroxysteroid Dehydrogenases: Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Sitosterols: A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Biliary Tract Diseases: Diseases in any part of the BILIARY TRACT including the BILE DUCTS and the GALLBLADDER.Cholestasis, Extrahepatic: Impairment of bile flow in the large BILE DUCTS by mechanical obstruction or stricture due to benign or malignant processes.3-alpha-Hydroxysteroid Dehydrogenase (B-Specific): A 3-hydroxysteroid dehydrogenase which catalyzes the reversible reduction of the active androgen, DIHYDROTESTOSTERONE to 5 ALPHA-ANDROSTANE-3 ALPHA,17 BETA-DIOL. It also has activity towards other 3-alpha-hydroxysteroids and on 9-, 11- and 15- hydroxyprostaglandins. The enzyme is B-specific in reference to the orientation of reduced NAD or NADPH.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Sulfuric Acids: Inorganic and organic derivatives of sulfuric acid (H2SO4). The salts and esters of sulfuric acid are known as SULFATES and SULFURIC ACID ESTERS respectively.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Jejunum: The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum.Intestine, Small: The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.Intestinal Secretions: Fluids originating from the epithelial lining of the intestines, adjoining exocrine glands and from organs such as the liver, which empty into the cavity of the intestines.Micelles: Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Liver Diseases: Pathological processes of the LIVER.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Psyllium: Dried, ripe seeds of PLANTAGO PSYLLIUM; PLANTAGO INDICA; and PLANTAGO OVATA. Plantain seeds swell in water and are used as demulcents and bulk laxatives.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.Glucuronates: Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Mesocricetus: A genus of the family Muridae having three species. The present domesticated strains were developed from individuals brought from Syria. They are widely used in biomedical research.Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains.Salt-Tolerance: The ability of organisms to sense and adapt to high concentrations of salt in their growth environment.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.1-Naphthylisothiocyanate: A tool for the study of liver damage which causes bile stasis and hyperbilirubinemia acutely and bile duct hyperplasia and biliary cirrhosis chronically, with changes in hepatocyte function. It may cause skin and kidney damage.Sulfobromophthalein: A phenolphthalein that is used as a diagnostic aid in hepatic function determination.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Ligation: Application of a ligature to tie a vessel or strangulate a part.Steroids: 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)

New perspectives on biliary atresia. (1/3564)

An investigation into the aetiology, diagnosis, and treatment of biliary atresia was carried out because the prognosis remains so poor.In an electron microscopical study no viral particles or viral inclusion bodies were seen, nor were any specific ultrastructural features observed. An animal experiment suggested that obstruction within the biliary tract of newborn rabbits could be produced by maternal intravenous injection of the bile acid lithocholic acid.A simple and atraumatic method of diagnosis was developed using(99) (m)Tc-labelled compounds which are excreted into bile. Two compounds, (99m)Tc-pyridoxylidene glutamate ((99m)Tc-PG) and (99m)Tc-dihydrothioctic acid ((99m)Tc-DHT) were first assessed in normal piglets and piglets with complete biliary obstruction. Intestinal imaging correlated with biliary tract patency, and the same correlation was found in jaundiced human adults, in whom the (99m)Tc-PG scan correctly determined biliary patency in 21 out of 24 cases. The (99m)Tc-PG scan compared well with liver biopsy and (131)I-Rose Bengal in the diagnosis of 11 infants with prolonged jaundice.A model of extrahepatic biliary atresia was developed in the newborn piglet so that different methods of bile drainage could be assessed. Priorities in biliary atresia lie in a better understanding of the aetiology and early diagnosis rather than in devising new bile drainage procedures.  (+info)

Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis. (2/3564)

Samples of serum, bile, and urine were collected simultaneously from patients with cholestasis of varying aetiology and from patients with cirrhosis; their bile acid composition was determined by gas/liquid chromatography and mass spectrometry. In cholestasis, the patterns in all three body fluids differed consistently and strikingly. In serum, cholic acid was the major bile acid and most bile acids (greater than 93%) were unsulphated, whereas, in urine, chenodeoxycholic was the major bile acid, and the majority of bile acids (greater than 60%) were sulphated. Secondary bile acids were virtually absent in bile, serum, and urine. The total amount of bile acids excreted for 24 hours correlated highly with the concentration of serum bile acids; in patients with complete obstruction, urinary excretion averaged 71-6 mg/24 h. In cirrhotic patients, serum bile acids were less raised, and chenodeoxycholic acid was the predominant acid. In healthy controls, serum bile acids were consistently richer in chenodeoxycholic acid than biliary bile acids, and no bile acids were present in urine. No unusual monohydroxy bile acids were present in patients with primary biliary cirrhosis, but, in several patients, there was a considerable amount of hyocholic acid present in the urinary bile acids. The analyses of individual bile acids in serum and urine did not appear to provide helpful information in the differential diagnosis of cholestasis. Thus, in cholestasis, conjugation of chenodeoxycholic acid with sulphate becomes a major biochemical pathway, urine becomes a major route of bile acid excretion, and abnormal bile acids are formed.  (+info)

A new hydrolase specific for taurine-conjugates of bile acids. (3/3564)

Through the investigation of the bile acid-deconjugation activities of human intestinal anaerobes, a new enzyme was discovered in Peptostreptococcus intermedius which hydrolyzed specifically the taurine-conjugates, but not the glycine-conjugates of bile acids. However, the enzymes in Streptococcus faecalis and Lactobacillus brevis hydrolyzed chiefly the glycine-conjugates.  (+info)

Effect of meat (beef, chicken, and bacon) on rat colon carcinogenesis. (4/3564)

High intake of red meat or processed meat is associated with increased risk of colon cancer. In contrast, consumption of white meat (chicken) is not associated with risk and might even reduce the occurrence of colorectal cancer. We speculated that a diet containing beef or bacon would increase and a diet containing chicken would decrease colon carcinogenesis in rats. One hundred female Fischer 344 rats were given a single injection of azoxymethane (20 mg/kg i.p.), then randomized to 10 different AIN-76-based diets. Five diets were adjusted to 14% fat and 23% protein and five other diets to 28% fat and 40% protein. Fat and protein were supplied by 1) lard and casein, 2) olive oil and casein, 3) beef, 4) chicken with skin, and 5) bacon. Meat diets contained 30% or 60% freeze-dried fried meat. The diets were given ad libitum for 100 days, then colon tumor promotion was assessed by the multiplicity of aberrant crypt foci [number of crypts per aberrant crypt focus (ACF)]. The ACF multiplicity was nearly the same in all groups, except bacon-fed rats, with no effect of fat and protein level or source (p = 0.7 between 8 groups by analysis of variance). In contrast, compared with lard- and casein-fed controls, the ACF multiplicity was reduced by 12% in rats fed a diet with 30% bacon and by 20% in rats fed a diet with 60% bacon (p < 0.001). The water intake was higher in bacon-fed rats than in controls (p < 0.0001). The concentrations of iron and bile acids in fecal water and total fatty acids in feces changed with diet, but there was no correlation between these concentrations and the ACF multiplicity. Thus the hypothesis that colonic iron, bile acids, or total fatty acids can promote colon tumors is not supported by this study. The results suggest that, in rats, beef does not promote the growth of ACF and chicken does not protect against colon carcinogenesis. A bacon-based diet appears to protect against carcinogenesis, perhaps because bacon contains 5% NaCl and increased the rats' water intake.  (+info)

Enrichment of canalicular membrane with cholesterol and sphingomyelin prevents bile salt-induced hepatic damage. (5/3564)

These studies were undertaken to characterize the role of plasma membrane cholesterol in canalicular secretory functions and hepatocyte integrity against intravenous taurocholate administration. Cholesterol and sphingomyelin concentrations and cholesterol/phospholipid ratios were significantly increased in canalicular membranes of diosgenin-fed rats, suggesting a more resistant structure against solubilization by taurocholate. During taurocholate infusion, control rats had significantly decreased bile flow, whereas diosgenin-fed animals maintained bile flow. Maximal cholesterol output increased by 176% in diosgenin-fed rats, suggesting an increased precursor pool of biliary cholesterol in these animals. Maximal phospholipid output only increased by 43% in diosgenin-fed rats, whereas bile salt output remained at control levels. The kinetics of glutamic oxalacetic transaminase, lactic dehydrogenase, and alkaline phosphatase activities in bile showed a significantly faster release in control than in diosgenin-fed rats. After 30 min of intravenous taurocholate infusion, necrotic hepatocytes were significantly increased in control animals. Preservation of bile secretory functions and hepatocellular cytoprotection by diosgenin against the intravenous infusion of toxic doses of taurocholate was associated with an increased concentration of cholesterol and sphingomyelin in the canalicular membrane. The increase of biliary cholesterol output induced by diosgenin was correlated to the enhanced concentration of cholesterol in the canalicular membrane.  (+info)

Evidence for an anion exchange mechanism for uptake of conjugated bile acid from the rat jejunum. (6/3564)

Absorption of conjugated bile acids from the small intestine is very efficient. The mechanisms of jejunal absorption are not very well understood. The aim of this study was to clarify the mechanism of absorption of conjugated bile acid at the apical membrane of jejunal epithelial cells. Brush-border membrane vesicles from intestinal epithelial cells of the rat were prepared. Absorption of two taurine-conjugated bile acids that are representative of endogenous bile acids in many variate vertebrate species were studied. In ileal, but not jejunal brush-border membrane vesicles, transport of conjugated bile acids was cis-stimulated by sodium. Transport of conjugated bile acids was trans-stimulated by bicarbonate in the jejunum. Absorption of conjugated dihydroxy-bile acids was almost twice as fast as of trihydroxy-bile acids. Coincubation with other conjugated bile acids, bromosulfophthalein, and DIDS, as well as by incubation in the cold inhibited the transport rate effectively. Absorption of conjugated bile acids in the jejunum from the rat is driven by anion exchange and is most likely an antiport transport.  (+info)

Role of cholesterol ester mass in regulation of secretion of ApoB100 lipoprotein particles by hamster hepatocytes and effects of statins on that relationship. (7/3564)

Our understanding of the factors that regulate the secretion of apoB100 lipoproteins remains incomplete with considerable debate as to the role, if any, for cholesterol ester in this process. This study examines this issue in primary cultures of hamster hepatocytes, a species in which both cholesterol and apoB100 metabolism are very similar to man. Addition of oleate to medium increased the mass of triglyceride and cholesterol ester within the hepatocyte and also increased the secretion of triglycerides, cholesterol ester, and apoB100 into the medium. Next, the responses of hamster hepatocytes to addition of either an HMG-CoA reductase inhibitor (lovastatin) or an acyl-CoA cholesterol acyltransferase inhibitor (58-035) to the medium, with or without added oleate, were determined. Effects of either agent were only evident in the oleate-supplemented medium in which cholesterol ester mass had been increased above basal. If oleate was not added to the medium, neither agent reduced apoB100 secretion; equally important, over the 24-hour incubation, neither agent, at the concentration used, produced any detectable change in intracellular cholesterol ester mass. However, in contrast to the estimates of mass, which were unchanged, under the same conditions radioisotopic estimates of cholesterol ester synthesis were markedly reduced. Any conclusion as to the relation of cholesterol ester mass to apoB100 secretion would therefore depend on which of the 2 methods was used. Overall, the data indicate a close correlation between the mass of cholesterol ester within the hepatocyte and apoB100 secretion from it and they go far to explain previous apparently contradictory data as to this relation. More importantly, though, taken with other available data, they indicate that the primary response of the liver to increased delivery of lipid is increased secretion rather than decreased uptake. These results point, therefore, to a hierarchy of hepatic responses to increased flux of fatty acids and increased synthesis of cholesterol that in turn suggests a more dynamic model of cholesterol homeostasis in the liver than has been appreciated in the past.  (+info)

The osmoprotectant glycine betaine inhibits salt-induced cross-tolerance towards lethal treatment in Enterococcus faecalis. (8/3564)

The response of Enterococcus faecalis ATCC 19433 to salt stress has been characterized previously in complex media. In this report, it has been demonstrated that this bacterium actively accumulates the osmoprotectant glycine betaine (GB) from salt-enriched complex medium BHI. To further understand the specific effects of GB and other osmoprotective compounds in salt adaptation and salt-induced cross-tolerance to lethal challenges, a chemically defined medium lacking putative osmoprotectants was used. In this medium, bacterial growth was significantly reduced by increasing concentrations of NaCl. At 0.75 M NaCl, 90% inhibition of the growth rate was observed; GB and its structural analogues restored growth to the non-salt-stressed level. In contrast, proline, pipecolate and ectoine did not allow growth recovery of stressed cells. Kinetic studies showed that the uptake of betaines shows strong structural specificity and occurs through a salt-stress-inducible high-affinity porter [Km = 3.3 microM; Vmax = 130 nmol min(-1) (mg protein)(-1); the uptake activity increased 400-fold in the presence of 0.5 M NaCl]. Moreover, GB and its analogues were accumulated as non-metabolizable cytosolic osmolytes and reached intracellular levels ranging from 1-3 to 1.5 micromol (mg protein)(-1). In contrast to the beneficial effect of GB on the growth of salt-stressed cultures of E. faecalis, its accumulation inhibits the salt-induced cross-tolerance to a heterologous lethal challenge. Indeed, pretreatment of bacterial cells with 0.5 M NaCl induced resistance to 0.3% bile salts (survival of adapted cells increased by a factor of 6800). The presence of GB in the adaptation medium reduced the acquisition of bile salts resistance 680-fold. The synthesis of 11 of the 13 proteins induced during salt adaptation was significantly reduced in the presence of GB. These results raise questions about the actual beneficial effect of GB in natural environments where bacteria are often subjected to various stresses.  (+info)

A simple, precise and sensitive method for separation and determination of total bile acid sulfates in human urine is described. The sulfate fraction of urinary bile acids was separated with lipophilic anion exchange gel, piperidinohydroxypropyl Sephadex LH-20 after sample clean-up with Sep-Pak C18 cartridge. The obtained sulfate fraction was submitted to solvolysis with a small volume of dimethoxypropane-HCl solution and subjected to enzymatic-fluorimetrical assay using 3 alpha-hydroxysteroid dehydrogenase and resazurin. In this method, no influence of existing salts in the reaction mixture on fluorescence intensity was observed and solvolysis reaction was almost complete. Overall recoveries of glycine- and taurine-conjugated bile acid 3-sulfates from normal urine ranged from 90.5 to 93.7% and those of unconjugates from 48.7 to 78.0%. The sensitivity of the described method enabled to estimate total bile acid sulfates with 0.5 ml of normal urine and precision tests showed the satisfactory accuracy. The
Since the last International Bile Acid Meeting in Freiburg in 1996, considerable progress has been made in several areas of bile acid research. The different pathways of bile acid synthesis and their regulation have been further characterized. The molecular mechanisms for biliary secretion of bile acids have been elucidated and genetic defects of bile acid transport have been defined. Injurious as well as protective effects of different bile acids on the liver have been further studied. Finally, the beneficial effects of ursodeoxycholic acid in cholestatic liver diseases have been substantiated and the potential mechanisms of action have been explored. This book, the proceedings of the Falk Symposium No. 108 (XV International Bile Acid Meeting), held in Titisee, Germany, October 12-13, 1998, is dedicated to both basic and clinical aspects of bile acid research with a focus on bile acids and cholestasis.Bile Acids and Cholestasis - XV International Bile Acid Meeting, 1 was published 1999 under ...
Dec 22, 2005. SAN DIEGO, CA - Dec 22, 2005 - Diazyme Laboratories, a company that applies its proprietary enzyme technologies to develop low cost and high quality diagnostic products for clinical and research uses, announced today that the U.S. Food and Drug Administration (FDA) has granted Diazyme 510(K) clearance to market its Enzymatic Total Bile Acids (TBA) Assay Kit for the quantitative determination of total bile acids in human blood samples.. Total bile acids is a well known bio-marker for diagnosis of liver diseases. Serum total bile acids are elevated in patients with acute hepatitis, chronic hepatitis, liver sclerosis, and liver cancer. Total bile acids levels are found to be the most sensitive indicator for monitoring the effectiveness of interferon treatment of chronic hepatitis C patients. Moreover, total bile acids tests are also widely used to screen pregnant women for the condition of obstetric cholestasis, a disease that is caused by elevated total bile acids in the bloodstream ...
Bile acids are C24 steroids that are derived in the liver from cholesterol and secreted into the intestinal lumen to aid in emulsification of dietary lipids and lipid-soluble vitamins. The indigenous intestinal microflora modify bile acids, producing up to 20 unique bile acid metabolites. The 7α-dehydroxylation of the bile acids is the most physiologically important bile acid biotransformation. All known intestinal bacteria capable of bile acid 7α-dehydroxylation are anaerobic, gram-positive rods of the genera Clostridium and Eubcicterium. Bile acid 7α-dehydroxylating bacteria often contain bile salt hydrolase, which hydrolyzes the peptide bond in taurine-conjugated bile acids to yield a free bile acid and taurine. Taurine is an organosulfonate containing a sulfite moiety. There have been no published reports indicating whether 7α-dehydroxylating bacteria can utilize taurine. Given that taurine and taurine-conjugated bile acids are found at great concentrations in the intestine, the ability to
Faecal bile acid excretion and intestinal transit time were studied in 18 children with inflammatory bowel disease in clinical remission and with normal stools: 16 with ulcerative colitis, two with Crohns colitis, mean age 14 years (range 10-17 years). Five healthy children, mean age 12.4 years (range 10-17 years), were studied as control subjects. Most patients were taking sulphasalazine, but none were taking steroids. Transit time was determined by carmine and did not differ between groups. Faeces were collected for 72 hours, and faecal water was prepared by centrifugation of faeces at 15,000 x g for two hours. Bile acids in total faeces and faecal water were studied using capillary gas-liquid chromatography-mass spectrometry. Faecal excretion of total bile acids, unconjugated bile acids, and glycine and taurine conjugates were significantly increased in patients as was faecal water excretion of total bile acids, particularly the taurine conjugates and cholic and chenodeoxycholic acids. Total ...
The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 +/- 4.84 micromol/l) than in
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 ...
Bile acids are usually found conjugated to glycine or taurine, a derivative of cysteine. Cells require the presence of an active bile acid transporter for uptake of these conjugated derivatives (10). To test whether conjugated bile acids would also activate FXR, we coexpressed the human ileal bile acid transporter (IBAT) with FXR in CV-1 cells (11). FXR was strongly activated by 3 μM of the taurine or glycine conjugates of CDCA, LCA, and DCA (Fig. 2G). Weaker activation was seen with the conjugated forms of CA, and tauro-MCA was inactive (Fig. 2G). These data indicate that FXR can be activated by conjugated bile acids in tissues that express bile acid transporters such as the terminal ileum, liver, and kidney. The relation between the chemical structure of bile acids and their activation of FXR is in close agreement with the reported effects of bile acids on induction of I-BABP expression in Caco-2 cells and inhibition of Cyp7a expression in hepatocytes (3, 12). Coactivator proteins interact ...
Chenodeoxycholoyl-CoA is bile acid Coenzyme A ester. In humans, bile acids conjugated with glycine and taurine are the major solutes in bile, and unconjugated bile acids are almost nondetectable in normal bile. Conjugated bile acids are less toxic and are more efficient promoters of intestinal absorption of dietary lipid than unconjugated bile acids. The synthesis of bile acid and amino acid conjugates in human liver is the result of two independent enzymatic reactions with a bile acid coenzyme A thioester intermediate formation of bile acid-CoA esters, considered the rate-limiting step in bile acid amidation and catalyzed by an ATP-dependent microsomal enzyme, bile acid-CoA synthetase (EC 6.2.1.7). In the second reaction, the thioester bond is cleaved, and an amide bond is formed between the bile acid and the amino acids glycine or taurine. The bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1.65) catalyzes this reaction in the cytosol prior to secretion into bile. In human liver the ...
1. The biliary excretion of total bilirubin and bile acids, and the fate of tracer doses of radioactive sulphated and non-sulphated bile acids, were studied in patients with percutaneous transhepatic bile drainage.. 2. Non-sulphated bile acids were excreted in bile early after biliary decompression, and the serum total 3α-hydroxy bile acid concentrations fell rapidly to normal. Biliary bilirubin excretion was both less than and delayed compared with that of bile acids, and the serum bilirubin concentration fell more slowly.. 3. The serum disappearance of [3H]chenodeoxycholate-3-sulphate was slower than that of [14C]glycocholate in all patients with bile drainage, the difference being more marked in the jaundiced patients.. 4. The radioactive sulphated bile acids were recovered predominantly in the urine of the jaundiced patients. In contrast [14C]glycocholate was excreted almost exclusively in bile. In an anicteric patient, radioactive sulphated bile acid disappeared from the serum more ...
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 ...
The secondary bile acids are derived from the primary bile acids by the enzymatic action of intestinal bacteria through the process of deconjugation and dehydroxylation. The secondary bile acids in humans include deoxycholic acid and lithocholic acid, formed from the 7alpha-dehydroxylation of cholic acid and chenodeoxycholic acid, respectively ...
Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with ...
Bile acids have been suggested to play an important role in the etiology of colon and gastric cancer after gastrectomy, but the molecular biology of these effects is poorly understood. We evaluated the effect of different bile acids on human gastric and colon carcinoma cells and identified genes by RNA arbitrarily primed PCR for differential display that are modulated following treatment with hydrophobic bile acids. Thioredoxin reductase (TR) mRNA was upregulated after treatment with taurochenodeoxycholic acid (TCDCA) in St 23132 cells. This raised the question whether deoxycholic acid (DCA) would have regulative effects on TR in HT-29 cells. After an incubation time of 6 h with DCA, TR mRNA expression was increased up to threefold. Ursodeoxycholic acid had no influence on TR mRNA expression. The upregulation of TR after DCA incubation was almost identical to incubation with 12-O-tetradecanoylphorbol-13-acetate. This implies that hydrophobic bile acids mediate oxidative stress in ...
The serum concentration of TBA in healthy neonates significantly exceeds that in children over 1 year of age, a condition called physiological cholestasis.9 The urinary TBA:creatinine ratio was raised in the first week after birth, then decreased gradually. The high concentration of TBA in urine may be attributable to either an enhanced stimulation of the enterohepatic circulation of bile acids or an impaired hepatic clearance or excretion.10The highest value for TBA in meconium was in neonates. This value is greatly influenced by events or conditions during pregnancy, such as the presence of biliary bile in the fetal duodenum or the ingestion of amniotic fluid by the fetus.10 11 Ketonic bile acids are usually considered to result from the bacterial oxidation of primary bile acids.12 In this study we detected ketonic bile acids early in life. The intestine may be colonised by bacterial flora during the first week.13 A high concentration of 3-oxo Δ4 bile acids in serum or urine has been ...
Hyocholic acid is a bile acid. Bile acids are steroid acids found predominantly in the bile of mammals. The distinction between different bile acids is minute, depending only on the presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. 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. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are ...
1] Islam KB, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81.. [2] Hellström PM, et al. Role of bile in regulation of gut motility. J Intern Med. 1995 Apr;237(4):395-402.. [3] Trauner M, et al. Bile acids as regulators of hepatic lipid and glucose metabolism. Dig Dis. 2010;28(1):220-4.. [4] Watanabe M, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006 Jan 26;439(7075):484-9.. [5] Zhou H, Hylemon PB. Bile acids are nutrient signaling hormones. Steroids. 2014 Aug;86:62-8.. [6] McMillin M, DeMorrow S. Effects of bile acids on neurological function and disease. FASEB J. 2016 Nov;30(11):3658-68.. [7] Fiorucci S, Distrutti E. Bile acid-activated receptors,iIntestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med. 2015 Nov;21(11):702-14.. [8] de Aguiar Vallim TQ, et al. Pleiotropic roles of bile acids in metabolism. Cell Metab. ...
Bile acids are steroidal amphipathic molecules derived from the catabolism of cholesterol. 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. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. Individual bile acid carriers have now been cloned from several species. Na(+)-dependent transporters that mediate uptake into hepatocytes and reabsorption from the intestine and biliary epithelium and an ATP-dependent transporter that pumps bile acids into bile comprise the classes of transporter that are specific for bile acids. In addition, at least four human and five rat genes that code for Na(+)-independent organic anion carriers with ...
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 ...
The enterohepatic circulation of bile acids is one of the most efficient recycling routes in the human body. It is a complex process involving numerous transport proteins, which serve to transport bile acids from the small intestine into portal circulation, from the portal circulation into the hepatocyte, from the hepatocyte into the bile, and from the gall bladder to the small intestine. The tremendous transport capacity and organ specificity of enterohepatic circulation combined with versatile derivatization possibilities, rigid steroidal backbone, enantiomeric purity, availability, and low cost have made bile acids attractive tools in designing pharmacological hybrid molecules and prodrugs with the view of improving intestinal absorption, increasing the metabolic stability of pharmaceuticals, specifically targeting drugs to organs involved in enterohepatic circulation, as well as sustaining therapeutically reasonable systemic concentrations of active agents. This article briefly describes bile acid
The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as ...
The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as ...
We have demonstrated in vitro the efficacy of the taurine-conjugated dihydroxy bile salts deoxycholate and chenodeoxycholate in solubilizing both cholesterol and phospholipid from hamster liver bile-canalicular and contiguous membranes and from human erythrocyte membrane. On the other hand, the dihydroxy bile salt ursodeoxycholate and the trihydroxy bile salt cholate solubilize much less lipid. The lipid solubilization by the four bile salts correlated well with their hydrophobicity: glycochenodeoxycolate, which is more hydrophobic than the tauro derivative, also solubilized more lipid. All the dihydroxy bile salts have a threshold concentration above which lipid solubilization increases rapidly; this correlates approximately with the critical micellar concentration. The non-micelle-forming bile salt dehydrocholate solubilized no lipid at all up to 32 mM. All the dihydroxy bile acids are much more efficient at solubilizing phospholipid than cholesterol. Cholate does not show such a pronounced ...
Dietary nutrients interact with gene networks to orchestrate adaptive responses during metabolic stress. Here, we identify Baf60a as a diet-sensitive subunit of the SWI/SNF chromatin-remodeling complexes in the mouse liver that links the consumption of fat- and cholesterol-rich diet to elevated plasma cholesterol levels. Baf60a expression was elevated in the liver following feeding with a western diet. Hepatocyte-specific inactivation of Baf60a reduced bile acid production and cholesterol absorption, and attenuated diet-induced hypercholesterolemia and atherosclerosis in mice. Baf60a stimulates expression of genes involved in bile acid synthesis, modification, and transport through a CAR/Baf60a feedforward regulatory loop. Baf60a is required for the recruitment of the SWI/SNF chromatin-remodeling complexes to facilitate an activating epigenetic switch on target genes. These studies elucidate a regulatory pathway that mediates the hyperlipidemic and atherogenic effects of western diet ...
Phospholipids and bile acids, by virtue of their amphiphilic properties, can interact in nonpolar media forming "inverted" structures (micelles) which presumably have an hydrophilic core and might act as diffusional carriers (ionophores) of electrolytes across low dielectric constant media or lipid membranes.. The Na+ ionophoretic capability of various purified phospholipids and the modulating effects of bile acids and phospatidylcholine was examined by: (a) measurement of 22Na+ partition into the organic phase (chloroform) of a two-phase system and (b) direct measurement of the translocation of 22Na+ across a bulk chloroform phase separating two aqueous phases in a Pressman cell. All phospholipids tested, except for phosphatidylcholine, showed ionophoretic capability for Na+ at micromolar concentrations. Cardiolipin and phosphatidylserine were the most efficient Na+ carriers, comparable with monensin, an established Na+ ionophore. In contrast, cholic acid as well as other bile acids ...
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 ...
Andriamiarina, R.; Laraki, L.; Pelletier, X.; Debry, G., 1989: Effects of stigmasterol-supplemented diets on fecal neutral sterols and bile acid excretion in rats
x] J Biol Chem. 2011 Aug 12;286(32):28382-95. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. Liaset B, Hao Q, Jørgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhøffer M, Li R, Li Q, Yde CC, Criales G, Bertram HC, Mellgren G, Ofjord ES, Lock EJ, Espe M, Frøyland L, Madsen L, Kristiansen K. "Bile acids (BAs)3 are synthesized in the liver from cholesterol. After their synthesis, they are conjugated to the amino acids taurine or glycine in a species-dependent manner (1). Conjugation of bile acids increases their solubility and facilitates their secretion into bile (2). [...] the dietary levels of these amino acids might be crucial for BA conjugation and secretion [...] In conclusion, we provide compelling evidence that plasma bile acid levels can be modulated by the dietary protein source in high fat-treated rats. Increased levels of plasma BAs were associated with a significant reduction in diet-induced ...
x] J Biol Chem. 2011 Aug 12;286(32):28382-95. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. Liaset B, Hao Q, Jørgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhøffer M, Li R, Li Q, Yde CC, Criales G, Bertram HC, Mellgren G, Ofjord ES, Lock EJ, Espe M, Frøyland L, Madsen L, Kristiansen K. "Bile acids (BAs)3 are synthesized in the liver from cholesterol. After their synthesis, they are conjugated to the amino acids taurine or glycine in a species-dependent manner (1). Conjugation of bile acids increases their solubility and facilitates their secretion into bile (2). [...] the dietary levels of these amino acids might be crucial for BA conjugation and secretion [...] In conclusion, we provide compelling evidence that plasma bile acid levels can be modulated by the dietary protein source in high fat-treated rats. Increased levels of plasma BAs were associated with a significant reduction in diet-induced ...
This gene encodes a member of the G protein-coupled receptor (GPCR) superfamily. This protein functions as a cell surface receptor for bile acids. Treatment of cells expressing this GPCR with bile acids induces the production of intracellular cAMP, activation of a MAP kinase signaling pathway, and internalization of the receptor. The receptor is implicated in the suppression of macrophage functions and regulation of energy homeostasis by bile acids.[2] One effect of this receptor is to activate deiodinases which convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). T3 in turn activates the thyroid hormone receptor which increases metabolic rate.[3][4] ...
The primary bile acids (BAs) are synthetized from colesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat, as well as bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolism by activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue ...
Alterations in glucocorticoid (GC) biosynthesis and metabolism are associated with a variety of pathophysiological disorders including cholestasis, diabetes and other metabolic disorders. Bile acids (BA) are also important modulators of metabolic functions and regulate cholesterol, triglyceride and glucose homeostasis as well as being critical for dietary fat digestion, enterohepatic function, and postprandial thermogenesis. In intact cells and in vivo, the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts inactive GC precursors (cortisone in humans, and 11-dehydrocorticosterone in mice and rats) into their active forms (cortisol and corticosterone, respectively) thereby amplifying local intracellular GC levels. Interconversion by 11β-HSD1 of other sterols has also been described. These include conversions of 7keto-cholesterol to 7β-hydroxycholesterol, 7-oxodehydroepiandrosterone (7-oxo-DHEA) to 7α-hydroxy- and 7β-hydroxy DHEA, 7- oxo-lithocholic acid (LCA, a bile acid; ...
Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids.
The invention relates to tetrazole derivatives of bile acids, processes for their preparation, and use of these compounds as medicaments and cholesterol lowering agents. The tetrazole-bile acid derivatives are of the formula G1--X--G2, where G1 is H, a bile acid radical, or a bile acid radical which is modified on the hydroxyl functions and/or on the carboxyl group, X is a single bond or a bridge group between G1 and G2, and G2 is of the formula: ##STR1##
Acyl-CoA synthetase involved in bile acid metabolism. Proposed to catalyze the first step in the conjugation of C24 bile acids (choloneates) to glycine and taurine before excretion into bile canaliculi by activating them to their CoA thioesters. Seems to activate secondary bile acids entering the liver from the enterohepatic circulation. In vitro, also activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol.
Obeticholic acid (abbreviated to OCA, trade name Ocaliva), is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a drug to treat primary biliary cholangitis, and is undergoing development for several other liver diseases and related disorders. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma. The natural bile acid, chenodeoxycholic acid, was identified in 1999 as the most active physiological ligand for the farnesoid X receptor (FXR), which is involved in many physiological and pathological processes. A series of alkylated bile acid analogues were designed, studied and patented by Roberto Pellicciari and colleagues at the University of Perugia, with 6α-ethyl-chenodeoxycholic acid emerging as the most highly potent FXR agonist. FXR-dependent processes in liver and intestine were proposed as therapeutic targets in human diseases. ...
Organic anion transporting polypeptides (OATPs) are uptake transporters for a broad range of endogenous compounds and xenobiotics. To investigate the physiologic and pharmacologic roles of OATPs of the 1A and 1B subfamilies, we generated mice lacking all established and predicted mouse Oatp 1a/1b transporters (referred to as Slco1a/1b(-/-) mice, as SLCO genes encode OATPs). Slco1a/1b(-/-) mice were viable and fertile but exhibited markedly increased plasma levels of bilirubin conjugated to glucuronide and increased plasma levels of unconjugated bile acids. The unexpected conjugated hyperbilirubinemia indicates that Oatp1a/1b transporters normally mediate extensive hepatic reuptake of glucuronidated bilirubin. We therefore hypothesized that substantial sinusoidal secretion and subsequent Oatp1a/1b-mediated reuptake of glucuronidated compounds can occur in hepatocytes under physiologic conditions. This alters our perspective on normal liver functioning. Slco1a/1b(-/-) mice also showed drastically ...
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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 …
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Farnesoid X receptor (FXR, NR1H4) is a ligand activated transcription factor belonging to the nuclear receptor (NR) superfamily, and is highly expressed in the liver, intestine, and kidney, in both humans and rodents. Bile acids (BAs) are the endogenous ligands of FXR. FXR mainly functions as the BA sensor by regulating genes that are critically involved in BA homeostasis. FXR has also been shown to play important roles in lipid, cholesterol and glucose metabolism, as well as inflammation, tumorigenesis, and liver regeneration. FXR deficiency is implicated in numerous liver diseases and mice with modulation of FXR have been used as animal models to study liver physiology and pathology. Genome-wide studies in mouse livers and intestines suggest FXRs diverse and broadly tissue specific functions. In the first aim, we studied the genome-wide FXR binding and transcriptome profiles upon FXR activation in primary human hepatocytes (PHHs) and HepG2 cells. Chromatin immunoprecipitation followed by ...
Bile Acid Factors™ consists of a mixture of highly concentrated bile acids (also called bile salts), mostly in the conjugated form, from U.S. and/or New Zealan
The effect of exercise training on upregulation of molecular markers of bile acid metabolism in the liver of ovariectomized rats fed a cholesterol-rich diet
The IUPHAR/BPS Guide to Pharmacology. GPBA receptor - Bile acid receptor. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
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The fetal thyroid gland is active and secretes thyroid hormones from the 12th week. It is independent of maternal control, although maternal thyroid hormones do cross the placenta. Hypothyroidism This may present with fatigue, hair loss, dry skin, abnormal weight gain, poor appetite, cold intolerance, bradycardia and delayed tendon reflexes. If untreated, there is double the rate of spontaneous miscarriages and stillbirths compared to the normal population, as well as a risk of fetal neurological impairment. There is a positive family history in up to 50% of cases. Transaminases are increased (less than threefold), and alkaline phosphatase levels are raised (above normal pregnancy values). Bilirubin is usually < 100mamol/l,and there may be pale stools and dark urine. Serum total bile acid concentration is increased early in the disease and may be the optimum marker. There are no serious long-term maternal risks but there is a risk of preterm labour, fetal distress and intrauterine fetal death. ...
Glucuronidation is considered an important detoxification pathway of bile acids especially in cholestatic conditions. Glucuronides are less toxic than the parent free forms and are more easily excreted in urine.
In this work, we show that in nondiabetic subjects, plasma 12α-hydroxylated BAs are disproportionately increased in association with IR. This finding provides evidence that BA composition is altered within the normal range of insulin sensitivity, and is consistent with insulin-dependent regulation of the 12α-hydroxylase CYP8B1. Our prior work has shown that Cyp8b1 is a target gene of transcription factor FoxO1, whose ability to promote Cyp8b1 transcription is inhibited by insulin via Akt-dependent phosphorylation and nuclear exclusion of FoxO1 (12). These findings dovetail with earlier studies of BA composition, as increased 12α-hydroxylated BAs have been observed in mice lacking hepatic insulin receptors and rodent models of diabetes (13-17). Because FoxO is expected to be more active in IR, owing to decreased Akt-mediated nuclear exclusion, the finding that FoxO1 activates Cyp8b1 reveals a plausible mechanism for upregulation of 12α-hydroxylated BA synthesis in these models.. Surprisingly, ...
A chronic voluntary exercise paradigm, which mimics the exercise pattern of many humans, influences the hepatic clearance of several organic anions and a bile acid, whereas a neutral organic compound is seemingly unaffected. To extend these observations, the present work has evaluated in female Sprague-Dawley rats the effect of 6 weeks of voluntary running on the hepatobiliary elimination of endogenous bile acids and glutathione and exogenously injected rose bengal, digoxin, and acetaminophen. Inactive rats had mobility limited to their cages, whereas exercised rats had free access to a 44-in running wheel. In comparison to weight-matched sedentary rats, the exercised rats ran 4.3 +/- 0.3 miles/day, consumed 45% more food daily, had slightly greater liver/body weight ratios, and slightly elevated basal bile flow rates. Biliary excretion of endogenous bile acids was increased significantly, and excretion of reduced and oxidized glutathione was increased in exercised rats by 190% and 173% of ...
Bile acids, a structurally related group of molecules derived from cholesterol, have a long history as therapeutic agents in medicine, from treatment for primarily ocular diseases in ancient Chinese medicine to modern day use as approved drugs for certain liver diseases. Despite evidence supporting a neuroprotective role in a diverse spectrum of age-related neurodegenerative disorders, including several small pilot clinical trials, little is known about their molecular mechanisms or their physiological roles in the nervous system. We review the data reported for their use as treatments for neurodegenerative diseases and their underlying molecular basis. While data from cellular and animal models and clinical trials support potential efficacy to treat a variety of neurodegenerative disorders, the relevant bile acids, their origin, and the precise molecular mechanism(s) by which they confer neuroprotection are not known delaying translation to the clinical setting.
Falany, C.N., Johnson, M.R., Barnes, S. and Diasio, R.B. (1994). „Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase". J. Biol. Chem. 269: 19375-19379. PMID 8034703 ...
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.
NaturalHealth365) A UC Davis Health study has discovered a compelling relationship between liver health and gut bacteria. The study indicates that probiotics and bile acid receptor agonists could be useful in helping to prevent liver inflammation as well as treat and prevent more serious liver diseases.. For the study, mice were fed a typical Western diet that was high in sugar and fat. Not surprisingly, this resulted in liver inflammation, especially in the male mice studied. Interesting to note: liver inflammation was found to be even more pronounced in male mice that were lacking in the FXR (X receptor) - a key bile acid receptor.. How do antibiotics negatively affect gut bacteria?. In antibiotic-treated mice, bile acid and gut bacteria profiles were changed due to the effects of antibiotics in eliminating bile acid-generating bacteria. The research showed that reduced hepatic inflammation from antibiotics decreased bile acids, especially in males.. In addition, the study results suggest that ...
OST-OST (SLC51A and SLC51B) is a heteromeric organic solute transporter that was first isolated from the liver of a marine skate, Leukoraja erinacia, by Ballatori etal in a quest for a sodium-independent transporter of hepatic bile acid uptake.1 Subsequent studies identified SLC51A and B orthologues from mice and human beings. These 2 gene products are the only known members of this SLC family and are unique in requiring 2 subunits for function. Human SLC51A encodes for a 340amino acid protein with 7 membrane-spanning domains whereas SLC51B encodes for a 128amino acid single-membrane-spanning domain protein ...
In this study, led by Guadalupe Sabio, Alfonso Mora, and Roger J. Davis, mice whose livers do not contain the JNK1 and JNK2 proteins have been bred. "These proteins are activated when we overeat and are partly responsible for excess fat being stored in the liver (i.e. - fatty liver or steatosis), and for the development of insulin resistance," explained Dr. Sabio. The proteins are, therefore, "very significant for obesity and diabetes studies," she added. Researchers also found that these two proteins control the production of bile acids in the liver, which are essential for proper fat digestion and the absorption of fat-soluble vitamins (A, D, E and K). "A lack of JNK1 and JNK2 in the liver leads to changes in the enzymes responsible for metabolizing cholesterol and bile acids," said Dr. Mora. In the analyzed mice, "we have observed excess blood levels of bile acids." Researcher Elisa Manieri explained that, over time, this accumulation of bile acids has a "toxic effect" on the liver. Bile ...
Increased levels of intestinal bile acids (BAs) are a risk factor for colorectal cancer (CRC). Here, we show that the convergence of dietary factors (high-fat diet) and dysregulated WNT signaling (APC mutation) alters BA profiles to drive malignant transformations in Lgr5-expressing (Lgr5+) cancer stem cells and promote an adenoma-to-adenocarcinoma progression. Mechanistically, we show that BAs that antagonize intestinal farnesoid X receptor (FXR) function, including tauro-ß-muricholic acid (T-ßMCA) and deoxycholic acid (DCA), induce proliferation and DNA damage in Lgr5+ cells. Conversely, selective activation of intestinal FXR can restrict abnormal Lgr5+ cell growth and curtail CRC progression. This unexpected role for FXR in coordinating intestinal self-renewal with BA levels implicates FXR as a potential therapeutic target for CRC ...
... / M. Ogundare; S. Theofilopoulos; A. Lockhart; L.J. Hall; E. Arenas; J. Sjövall; A.G. Brenton; Y. Wang; W.J. Griffiths ...
Soluble, Viscous, Fermentable fiber is often recommended to those with high blood cholesterol for several reasons. 1. The liver makes cholesterol from bile salts. Bile Salts are like the detergent of the intestine- Soluble fiber grabs onto Bile Salts in the liver and blocks reabsorption of Bile Salts, helping to extract them to the…
TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies in vivo, we show …
By Ruth SoRelle, M.P.H. The road to liver cancer starts with a pile-up -- the toxic accumulation of bile acids that act as tumor promoters. This begins a deadly cascade that leads to overexpression of a protein called IQGAP1, which activates the Yes-associated protein (YAP), said researchers from Baylor College of Medicine in a report that…
Tenet Diagnostics provides Bile Acids Total, Serum test with the best diagnostic center lab and well trained staff and most accurate online reports.
Dietary factors, including bile acids, are important in the causation of colorectal cancer (CRC). We have previously shown that in vitro exposure of colorectal mucosal biopsies to low concentrations of bile acids produces apoptosis selectively in goblet cells. Apopotosis is an important mechanism for clearing DNA-damaged cells. Inhibition of apoptosis would result in increasing accumulation of DNA-damaged cells, resulting in increased cancer risk. We compared the percentage of apoptosis induced by bile acids in mucosal biopsies from CRC patients with that of noncancer subjects.. Mucosal biopsies from 15 to 20 cm from the anal verge were incubated in 1 mm sodium deoxycholate, and the percentage of goblet cells undergoing apoptosis was quantitated. Seven patients with a history of CRC within the previous 5 years were compared with 18 noncancer subjects [4 neoplasia free and 14 with small (≤9 mm) polyps only].. The CRC patients had a significantly lower percentage of apoptosis than noncancer ...
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Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M. Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. Biochem Biophys Res Commun. 2007 Mar 2;354(1):[http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBK-4MP5JGJ-C-9&_cdi=6713&_user=16764&_pii=S0006291X06028439&_origin=search&_coverDate=03%2F02%2F2007&_sk=996459998&view=c&wchp=dGLbVzb-zSkWb&md5=203a244a62ad6ef3293be26a9666deef&ie=/sdarticle.pdf 154-9]. (pmid=17214962 ...
Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M. Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. Biochem Biophys Res Commun. 2007 Mar 2;354(1):[http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBK-4MP5JGJ-C-9&_cdi=6713&_user=16764&_pii=S0006291X06028439&_origin=search&_coverDate=03%2F02%2F2007&_sk=996459998&view=c&wchp=dGLbVzb-zSkWb&md5=203a244a62ad6ef3293be26a9666deef&ie=/sdarticle.pdf 154-9]. (pmid=17214962 ...
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Used to assess liver function, identify occult liver disease, evaluate for vascular anomalies, and monitor patients on hepatotoxic medication.
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In addition to the well-known roles in development and maintenance of normal sexual and reproductive function, estrogen exerts a vast range of biological effect...
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CHO-RatGpbar1-FLAG is clonally-derived from a CHO-K1 cell line which has been transfected with a rat G protein-coupled bile acid receptor 1 (Gpbar1) tagged in the N-terminus with FLAG to allow stably express of the rat Gpbar1 tagged in the N-terminus with FLAG protein. It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplification system.
sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate: semisynthetic bile acid with hypoglycemic efects when given orally to type 1 diabetic rats
Goat polyclonal Bile Acid Receptor NR1H4 antibody validated for WB, ELISA and tested in Human and Rabbit. With 1 independent review. Immunogen corresponding to…
I had cholestasis with my dd, and was really hoping to be one of the lucky ones that dont get it a second time. Yesterday I was practically scratching my skin off. The itching is everywhere.... And still itchy today. I called my OB and have a bile acid test in the morning Im depressed knowing that i have this again. I know I do. I cant catch a break
Bile acids promote bile formation and facilitate dietary lipid absorption. Animal and human studies showing disturbed bile acid metabolism in diabetes mellitus suggest a link between bile acids and glucose control. Bile acids are activating ligands of the farnesoid X receptor (FXR), a nuclear receptor with an established role in bile acid and lipid metabolism. Evidence suggests a role for FXR also in maintenance of glucose homeostasis. Animal and human studies employing bile acid sequestrants (bile acid binding agents), which interrupt the enterohepatic circulation of bile acids and effectively reduce plasma cholesterol, support a link between bile acid and glucose metabolism. In lipid-lowering trials, bile acid sequestrants, such as colesevelam hydrochloride, colestyramine (cholestyramine) and colestilan (colestimide), have also been shown to lower plasma glucose and glycosylated haemoglobin levels, suggesting the utility of these agents as a potential therapy for type 2 diabetes. In this ...
Peroxisomal beta-oxidation is an essential step in bile acid synthesis, since it is required for shortening of C27-bile acid intermediates to produce mature C24-bile acids. D-Bifunctional protein (DBP) is responsible for the second and third step of this beta-oxidation process. However, both patients and mice with a DBP deficiency still produce C24-bile acids, although C27-intermediates accumulate. An alternative pathway for bile acid biosynthesis involving the peroxisomal L-bifunctional protein (LBP) has been proposed. We investigated the role of LBP and DBP in bile acid synthesis by analyzing bile acids in bile, liver, and plasma from LBP, DBP, and LBP:DBP double knock-out mice. Bile acid biosynthesis, estimated by the ratio of C27/C24-bile acids, was more severely affected in double knock-out mice as compared with DBP-/- mice but was normal in LBP-/- mice. Unexpectedly, trihydroxycholestanoyl-CoA oxidase was inactive in double knock-out mice due to a peroxisomal import defect, preventing us ...
Bile acid diarrhoea (BAD) is an under-recognised but common condition of chronic watery diarrhoea. BAD may be secondary to ileal disease affecting the reabsorption and the enterohepatic circulation of bile acids (bile acid malabsorption) or can be an idiopathic, primary BAD (PBAD). In work published in 2009, we described a new mechanism to explain this syndrome of primary BAD.. Blood levels of the hormone fibroblast growth factor 19 (FGF19) are reduced in primary and secondary BAD, producing impaired feedback inhibition of bile acid synthesis, leading to excess faecal bile acids, which then produce diarrhoea by stimulating colonic secretion. FGF19 is synthesised in the ileum and we have shown transcription is markedly induced by farnesoid X receptor(FXR) agonists such as chenodeoxycholic acid, an abundant natural bile acid. More potent FXR agonists are logical diagnostic and therapeutic agents for this condition, and obeticholic acid (OCA), which is 100x more potent than chenodeoxycholic acid, ...
TY - JOUR. T1 - Bile acid efflux mediated by the rat liver canalicular bile acid transport/ecto-ATPase protein requires serine 503 phosphorylation and is regulated by tyrosine 488 phosphorylation. AU - Sippel, C. Jeffrey. AU - Fallon, Robert J.. AU - Perlmutter, David H.. PY - 1994/7/29. Y1 - 1994/7/29. N2 - Transfection of cDNA for a hepatocyte canalicular phosphoprotein, the rat liver canalicular bile acid transporter/ecto-ATPase/cell CAM 105, confers bile acid efflux and ecto-ATPase activities on heterologous cells (Sippel, C. J., Suchy, F. J., Ananthanarayanan, M., and Perlmutter D. H. (1993) J. Biol. Chem. 268, 2083-2091). Our previous studies have also indicated that there is a positive correlation between the degree of phosphorylation of this transporter and its bile acid efflux activity. In this study, we introduced site-specific mutations of amino acid residues within a protein kinase C- dependent (T502A, S503A) and a tyrosine kinase-dependent (Y488F) phosphorylation consensus sequence ...
The fasting and postprandial serum concentrations of bile acids and other blood constituents were measured in a group of 10 clinically healthy, female, six-year-old captive red-eared terrapins (Trachemys scripta elegans). The terrapins were housed in a temperate room and maintained in four aquaria in which the water temperature ranged from 24 to 27°C and the temperature above the basking site ranged from 27 to 30°C. The serum concentrations of bile acids were measured four times in a period of five months, and at the second sampling the fasting and two postprandial (after 24 and 48 hours) serum concentrations of total protein, albumin, glucose, uric acid, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and bile acids were determined. Coelioscopy revealed vitellogenic and previtellogenic follicles on the ovaries of all the terrapins, and eggs with calcified shells were detected in two of them. The livers were mostly ...
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 (
1. Bile salt metabolism has been studied in seven patients with ileostomy following total proctocolectomy; three of these patients also had various degrees of ileal resection.. 2. The half-life of the cholic acid pool was shortened in the patients with ileal resection.. 3. Rates of bile acid synthesis were raised in two of the three patients with ileal resection. In the third, the rate was normal.. 4. Four of the six patients had low bile acid concentrations in the duodenum after a fatty meal.. 5. Deoxycholic acid could not be detected in the duodenum or ileal effluent of any of the patients.. ...
RESULTS: In 135 variably related Maltese, shunt status could be confirmed in 113, including 19 with anextra-hepatic portosystemic shunt (17 confirmed at surgery, 2 at necropsy). Rectal ammonia tolerance testing results and post-prandial serum bile acid concentrations were retrievable for 50 and 88 dogs, respectively. Pedigree information was available for these 135 and an additional 164 related dogs. Two consecutive test matings were carried out between two affected animals (whose shunts had been attenuated), with 2 of 8 (25%) of offspring having an extra-hepatic portosystemic shunt. Six test matings were carried out between an affected and an unaffected animal, with 2 of 22 (9%) offspring affected. Heritability of extra-hepatic portosystemic shunt was 0·61 calculated using variance components analysis [95% confidence interval (CI) 0·14 to 1·0, P=0·001]. The best fitting model from segregation analysis was a common, partially penetrant, recessive model (allele frequency 0·34, penetrance ...
Learn more about Bile Acid Sequestrant Drugs at Grand Strand Medical Center Many Nutrients - Supplementation Likely Helpful The bile acid sequestrant...
Bile Acid SequestrantsPatients with terminal ileal disease may not absorb bile acids normally, which can lead to secretory diarrhea in the colon. These patients may benefit from bile acid sequestrants... more
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TY - JOUR. T1 - Effects of deoxycholylglycine, a conjugated secondary bile acid, on myogenic tone and Agonist-Induced contraction in rat resistance arteries. AU - Khurana, Sandeep. AU - Raina, Hema. AU - Pappas, Valeria. AU - Raufman, Jean Pierre. AU - Pallone, Thomas L.. PY - 2012/2/16. Y1 - 2012/2/16. N2 - Background: Bile acids (BAs) regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT), a key determinant of systemic vascular resistance (SVR), have not been examined. Methodology/Principal Findings: Fourth-order mesenteric arteries (170-250 μm) isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 μM), a glycine-conjugated major secondary BA, induced reversible, concentration-dependent reduction of MT that was similar in endothelium-intact and ...
Background: Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17 beta-estradiol (E-2) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. Methods:HepG2 cells were exposed for 24 h to DCA (350 mu mol/L). Cell viability, aspartate aminotransferase and lactate dehydrogenase activity and apoptosis were measured as indices of cell toxicity. The effect of DCA was compared to that observed using either a hydrophilic bile acid, ursodeoxycholic acid (UDCA; 100 mu mol/L), or E-2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 mu mol/L) or mixtures of E-2/DCA or UDCA/DCA. The same experiments were performed using WRL-68 cells that, at variance with HepG2, express a higher level of nuclear estrogen receptor. Results:High concentrations of E-2 and UDCA prevented DCA-induced decrease in cell viability, increase in ...
Shop Acyl-coenzyme A amino acid N-acyltransferase ELISA Kit, Recombinant Protein and Acyl-coenzyme A amino acid N-acyltransferase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
More than 10 mutations in the AKR1D1 gene have been found to cause congenital bile acid synthesis defect type 2. This condition is characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Most of the AKR1D1 gene mutations replace single protein building blocks (amino acids) in the enzyme. These mutations result in production of a 3-oxo-5-β-steroid 4-dehydrogenase enzyme with severely reduced function. Without enough functional enzyme, the conversion of 7α-hydroxy-4-cholesten-3-one to 7α-hydroxy-5β-cholesten-3-one is impaired. The 7α-hydroxy-4-cholesten-3-one instead gets converted into abnormal bile acid compounds that cannot be transported out of the liver into the intestine, where the bile acids are needed to digest fats. This impaired production and release of bile acids leads to cholestasis. As a result, cholesterol and abnormal bile acids build up in the liver and fat-soluble vitamins are not absorbed, leading ...
Bile acid in the stomach plays a key role in the digestion of food in the small intestine. Two chief bile acids produced in the body include chenodeoxycholic acid and cholic acid. These acids assist in the creation of micelles, which aids in breaking down dietary fat, and is integral for the digestion of fat in the small intestine. Bile acid is a fluid secreted by the hepatocytes that flows into the canaliculi. From the canaliculi, it reaches the bile ducts, and is then transferred to the gall bladder where it is concentrated with time and the addition of other bodily fluids. Bile acids are derived from the cholesterol inside of the hepatocytem, and are made up of hydrophilic or polar faces and lipid or hydrophobic faces. Cholesterol gets converted into chenodeoxycholic and cholic acids, which are two forms of bile acid. These are combined with amino acids and released into the canaliculi. This combined nature of bile acids enables them to perform two of the most important functions in the ...
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 ...
The Na+-taurocholate cotransporting polypeptide (NTCP) is the predominant transporter responsible for bile acid uptake from portal blood across the basolateral membrane of hepatocytes. In rodent models of cholestasis, expression of the Ntcp mRNA and protein is notably decreased (22, 27, 104). Certain human diseases with a cholestatic component, such as primary biliary cirrhosis and cholestatic alcoholic hepatitis, are also associated with reduced NTCP expression (111, 112). Thus, in addition to enhancing bile acid efflux through induction of BSEP, bile acids suppress the expression of the major bile acid uptake system in conditions of elevated hepatocellular bile acid concentrations. It has been proposed that Fxr-induced Shp is responsible for decreased expression of Ntcp in rats through its interference with the retinoic acid receptor (Rar)-Rxr heterodimer, which has a binding site within the rat Ntcp promoter (16). The Rar-Rxr response element of the rat Ntcp promoter is not conserved in the ...
Epomediol (1,3,3-trimethyl-2-oxabicyclo(2.2.2.)octan-6,7-endo,endo-diol) (EPO) is a terpenoid compound shown to reverse 17 alpha-ethinylestradiol (EE)-induced cholestasis in rat. The effect is related to the restoration of normal liver plasma membrane fluidity values. To further characterize the effect of EPO, bile flow and biliary lipid composition were measured in rats treated either with EE or EE associated with EPO. EE significantly reduced the bile flow; this reduction was prevented by concomitant treatment with EPO with an increase in the bile salt secretion rate. EPO alone showed a choleretic effect. The biliary secretion rate of cholesterol was also significantly reduced by EE while being comparable to controls in EE-EPO-treated animals. Phospholipid (PL) biliary excretion was significantly (P less than 0.002) increased by EE either alone or combined with EPO. After EE treatment, the biliary PL composition showed a reduction in phosphatidylcholine (PC) concentration with a parallel ...
Increased serum bile salt levels have been associated to a single-nucleotide polymorphism in the bile salt export pump (BSEP; ABCB11) in several acquired cholestatic liver diseases but there is little evidence in alcoholic liver disease (ALD). Furthermore, a crosstalk between vitamin D and bile acid synthesis has recently been discovered. Whether this crosstalk has an influence on the course of ALD is unclear to date. Our aim was to analyse the role of genetic polymorphisms in BSEP and the vitamin D receptor gene (NR1I1) on the emergence of cirrhosis in patients with ALD. Therefore, 511 alcoholic patients (131 with cirrhosis and 380 without cirrhosis) underwent ABCB11 genotyping (rs2287622). Of these, 321 (131 with cirrhosis and 190 without cirrhosis) were also tested for NR1I1 polymorphisms (bat-haplotype: BsmI rs1544410, ApaI rs7975232 and TaqI rs731236). Frequencies of ABCB11 and NR1I1 genotypes and haplotypes were compared between alcoholic patients with and without cirrhosis and correlated ...
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] ...
1. The effects of phenobarbitone on cholesterol and bile acid metabolism have been examined in healthy humans.. 2. In three of four subjects the faecal excretion of bile acids was increased by phenobarbitone. This was associated with an increased pool size and turnover of cholic acid. Cholesterol excretion was not clearly affected. The fourth subject who did not respond was also exceptional in not showing an increase in the plasma clearance of antipyrine.. 3. The three responsive subjects also developed significant increases in plasma cholesterol and triglyceride concentrations. These findings were associated with an early rise in very-low-density lipoprotein and a fall in plasma cholesterol specific radioactivity in one patient, changes compatible with increased cholesterol synthesis. ...
BACKGROUND & AIMS: Oral administration of ursodeoxycholic acid (UDCA) and cholesterol causes bile salt malabsorption; the former by competition for and the latter by down-regulation of ileal bile acid transporters. Because ileectomy in rats induces enterohepatic cycling of bilirubin, the hypothesis that dietary steroids might have the same effect was tested. METHODS: Male inbred C57L/J mice and Sprague-Dawley rats were fed low doses of UDCA, chenodeoxycholic acid (CDCA), or cholesterol added to laboratory chow with simultaneous chow-fed controls. After 1 week (mice) or 2 weeks (rats), indices of bile salt malabsorption and enterohepatic cycling of bilirubin were measured, including bilirubin secretion rates into bile, serum and intestinal bilirubin and bile salt levels, and urobilinogen levels in cecum, large intestine, and feces. RESULTS: Dietary UDCA and cholesterol, but not CDCA, significantly increased bilirubin secretion rates into bile. In UDCA-fed mice, gallbladder biles contained
Cystic fibrosis (CF) is one of the most frequently occurring life threatening congenital diseases. This progressive disease manifests itself in several organ systems. The disease is caused by a mutation in the CFTR protein. The studies in the thesis focused on the development and treatment of CF in the liver and intestine, in particular the role of bile salts. Bile salts are essential in metabolism and play a crucial role in intestinal dietary fat and vitamin absorption in the gut. The experiments were performed in mice models with a mutation in the CFTR protein. With respect to CF disease in the gut we found that a disturbance in the bile salt metabolism, together with e.g. changes in the intestinal microbial flora, could be related to the clinical finding of persistent decrease of intestinal fat absorption in CF, despite adequate medication. These findings could be related to the decreased growth in CF conditions. With respect to CF disease in the liver we found that the currently used ...
2H2O affects many membrane transport processes by solvent and kinetic isotope effects. Since bile formation is a process of osmotic filtration where such effects could be important, we investigated the effects of 2H2O on bile formation in the in situ perfused rat liver. Dose finding experiments showed that at high concentrations, 2H2O increased vascular resistance and induced cholestasis; at 60% 2H2O however, a clear dissociation between the vascular and biliary effects was observed. Therefore, further experiments were carried out at this concentration. The main finding was a reduction in bile salt-independent bile flow from 0.99 +/- 0.04 to 0.66 +/- 0.04 microliters.min-1.g-1 (P , 0.001). This was associated with a 40% reduction in biliary bicarbonate concentration (P , 0.001). Choleretic response to neither taurocholate nor ursodeoxycholate was altered by 2H2O; in particular, there was a similar stimulation of bicarbonate secretion by ursodeoxycholate in the presence of 60% 2H2O. To further ...
TY - JOUR. T1 - Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. AU - Watanabe, Mitsuhiro. AU - Houten, Sander M.. AU - Wang, Li. AU - Moschetta, Antonio. AU - Mangelsdorf, David J.. AU - Heyman, Richard A.. AU - Moore, David D.. AU - Auwerx, Johan. PY - 2004/1/1. Y1 - 2004/1/1. N2 - We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) α and β, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXRα and LXRβ. These results suggest that ...
Bile acid/Bile salt malabsorption *Terminal ileal disease such as Crohn's disease ... In addition, unabsorbed fatty acids, converted to hydroxy-fatty acids by colonic flora, as well as unabsorbed bile acids both ... 75SeHCAT test to diagnose bile acid malabsorption in ileal disease or primary bile acid diarrhea. ... Bile salt breath test (14C-glycocholate) to determine bile salt malabsorption. ...
The serum bile acid blood test for ICP is a quantitative measurement of bile salts. The results of this test often take longer ... To obtain a diagnosis of ICP, there are two LFT (liver function tests) and Serum bile acid test. The liver function tests (LFTs ... In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to ... This risk rose further if bile acids doubled, Maternal consequences include the following: Itching, which can become intense ...
"Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling". Nature Communications. 7: 11248. doi: ... It has been shown that autotaxin's function can be regulated by certain steroids, namely bile acids. Various small molecule ... The physiological function of autotaxin is the production of the signalling lipid lysophosphatidic acid (LPA) in extracellular ... Lysophosphatidic acid Lysophospholipid receptors Lipid signaling Phospholipases GRCh38: Ensembl release 89: ENSG00000136960 - ...
These salts are formed in the hepatocytes from bile acids combined with an amino acid. Other compounds such as the waste ... Bile is formed of three elements: bile salts, bilirubin and cholesterol. Bilirubin is a waste product of the breakdown of ... The bile salt component is an active non-enzymatic substance that facilitates fat absorption by helping it to form an emulsion ... Bile is secreted into the duodenum of the small intestine via the common bile duct. It is produced in liver cells and stored in ...
... bile salt hydrolase, and choloyltaurine hydrolase. This enzyme participates in bile acid biosynthesis. As of late 2007, 4 ... Stellwag EJ, Hylemon PB (1976). "Purification and characterization of bile salt hydrolase from Bacteroides fragilis subsp. ...
B. longum also has bile salt hydrolases to hydrolyze bile salts into amino acids and bile acids. The function of this is not ... longum could use the amino acids products to better tolerate bile salts. B. longum is a constituent in VSL#3. This proprietary ... Some strains of B. longum were found to have high tolerance for gastric acid and bile, suggesting that these strains would be ... Tanaka, H.; Hashiba, H.; Kok, J.; Mierau, I. (2000). "Bile salt hydrolase of Bifidobacterium longum-biochemical and genetic ...
Bile salt breath test (14C-glycocholate) to determine bile salt malabsorption. Schilling test to establish cause of B12 ... Cholestyramine or other bile acid sequestrants will help reducing diarrhoea in bile acid malabsorption. Fructose malabsorption ... In addition, unabsorbed fatty acids, converted to hydroxy-fatty acids by colonic flora, as well as unabsorbed bile acids both ... 75SeHCAT test to diagnose bile acid malabsorption in ileal disease or primary bile acid diarrhea. Glucose hydrogen breath test ...
Thumser AE, Wilton DC (December 1996). "The binding of cholesterol and bile salts to recombinant rat liver fatty acid-binding ... FABP1 is unique in the wider range of other hydrophobic ligands it can bind including bilirubin, monoglycerides, bile acids and ... "Decreased hepatic triglyceride accumulation and altered fatty acid uptake in mice with deletion of the liver fatty acid-binding ... "Binding of fatty acids and peroxisome proliferators to orthologous fatty acid binding proteins from human, murine, and bovine ...
Furthermore, a bile acid-picolinic acid conjugate can form gels in solvents that are 30%-50% organic. The increased water ... Oxalic acid dihydrate is another important ligand, that easily forms stable structures when copper salts are added, which can ... "Stimuli-responsive Bile Acid-based Metallogels Forming in Aqueous Media." Steroids 97 (2015): 54-61. Web. 1 Mar. 2016. Compel, ... As an example of a chemo-response, adding a small amount of formic acid to Zn/Eu will cause the breakdown of gel-like material ...
Mutations in EPHX1 have been linked with preeclampsia, elevated blood levels of bile salts (i.e. hypercholanemia), Fetal ... Ananthanarayanan M, von Dippe P, Levy D (1988). "Identification of the hepatocyte Na+-dependent bile acid transport protein ... EPHX1 mediates the sodium-dependent transport of bile acids into hepatocytes. Androstene oxide and epoxyestratrienol have been ... and cerebral metabolism of epoxyeicosatrienoic acids was suggested. Modulation of metabolism of epoxyeicosatrienoic acids by ...
Bile salts interfere with the gastric mucosal barrier, allowing acid to irritate the stomach lining and cause gastritis. Dogs ... Bilious vomiting syndrome in dogs is vomiting in response to bile-induced inflammation of the stomach. It is also known as ...
... on the properties of bile salts (over 500), and the mechanisms whereby bile acids produce secretion in the colon (over 400). ... His early studies on the role of bile acids in the formation of micelles, the structure of the mixed micelle, and bile acid ... "The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts". ... Hofmann AF (June 1961). "Micellar solubilization of fatty acids and monoglycerides by bile salt solutions". Nature. 190: 1106-7 ...
... most of the bile acids are ionized and mostly occur as their sodium salts which are then called "primary conjugated bile salts ... Bacteria deconjugate some of the primary and secondary conjugated bile salts back to lipid-soluble bile acids, which are ... Finally, the conjugated bile acids which remained un-ionized conjugated bile acids are passively absorbed. Venous blood from ... Hepatocytes metabolize cholesterol to cholic acid and chenodeoxycholic acid. These lipid-soluble bile acids are conjugated ( ...
Bile salts interfere with the gastric mucosal barrier, allowing acid to irritate the stomach lining and cause gastritis. ... Findings include the inability to concentrate urine, and the presence of glucose, protein, and amino acids in the urine. Renal ... There is more familiarity with the glucocortcoids, such as cortisol; mineralocorticoids control the amount of potassium, salt ... Bilious vomiting syndrome is vomiting in response to bile-induced inflammation of the stomach. ...
2007). "Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor ... 2007). "The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells.". Hepatology 45 (3): ... "Bile Acid Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. ... 2003). "A G protein-coupled receptor responsive to bile acids.". J. Biol. Chem. 278 (11): 9435-40. PMID 12524422. doi:10.1074/ ...
12α-dihydroxy-5β-cholan-24-oic acid, is a bile acid. Deoxycholic acid is one of the secondary bile acids, which are metabolic ... Sodium deoxycholate, the sodium salt of deoxycholic acid, is often used as a biological detergent to lyse cells and solubilise ... Bacteria metabolize chenodeoxycholic acid into the secondary bile acid lithocholic acid, and they metabolize cholic acid into ... There are additional secondary bile acids, such as ursodeoxycholic acid. Deoxycholic acid is soluble in alcohol and acetic acid ...
... see also steroidogenesis Fatty acids - see also fatty acid metabolism Bile salts Eicosanoids Glycolipids Ketone bodies ... Chemicals from the pancreas (pancreatic lipase family and Bile salt-dependent lipase) are transported to the small intestines ... King, Michael W. Fatty Acid, Omega-3 and Omega-6 Fatty Acid, Triglyceride, and Phospholipid Synthesis and Metabolism. The ... Fatty acid metabolism begins in the cytoplasm of epithelial cells as Acyl-CoA synthetase and hydrolysis of ATP cleaves a ...
Triacylglycerol + 2 H2O ⇌ {\displaystyle \rightleftharpoons } 2-monoacylglycerol + 2 fatty acid anions Bile salts secreted from ... "Colipase residues Glu64 and Arg65 are essential for normal lipase-mediated fat digestion in the presence of bile salt micelles ... loop of pancreatic lipase mediate lipase-colipase interactions in the presence of bile salt micelles". J. Biol. Chem. 281 (12 ... The resulting monomers (2 free fatty acids and one 2-monoacylglycerol) are then moved by way of peristalsis along the small ...
Resistance to gastric acid and bile acid are scientifically presented in the following studies where L. bulgaricus successfully ... lines Antimicrobial activity against potentially pathogenic bacteria Ability to reduce pathogen adhesion to surfaces Bile salt ... Resistance to gastric acidity Bile acid resistance Adherence to mucus and/or human epithelial cells and cell ... How can acids be applied so as to control the bacterial flora of the large intestine? Not in the ordinary way because, when ...
"The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts". ... Therefore, it is essential that fats are first emulsified by bile salts for optimal activity of these enzymes. The digestion ... The fatty acids in the fats obtained from land animals tend to be saturated, whereas the fatty acids in the triglycerides of ... Fatty acids are broken down to acetyl-CoA by means of beta oxidation inside the mitochondria, whereas fatty acids are ...
Bile salt diarrhea can also be a side-effect of gallbladder removal. Bile acid sequestrants are the principal therapy for bile ... Bile acid sequestrants exchange anions such as chloride ions for bile acids. By doing so, they bind bile acids and sequester ... with appropriate intervals between dosing of the vitamins and bile acid sequestrants. In addition to bile acids, bile acid ... Thus, bile acid sequestrants, along with any bile acids bound to the drug, are excreted via the feces after passage through the ...
This enzyme is involved in a metabolic pathway that degrades bile acids into cholesterol. MacDonald IA, Mahony DE, Jellet JF, ... Mahony DE, Meier CE, Macdonald IA, Holdeman LV (1977). "Bile salt degradation by nonfermentative clostridia". Appl. Environ. ...
... bile salts, 0.2% bilirubin, 0.51% fats (cholesterol, fatty acids and lecithin), and 200 meq/l inorganic salts. Bile was the ... Glycocholic acid Taurocholic acid Deoxycholic acid Lithocholic acid Medicine portal Animals portal Bile acid sequestrant Bile ... "Secretion of Bile and the Role of Bile Acids In Digestion". www.vivo.colostate.edu. Retrieved 2017-03-31. "Secretion of Bile ... "Secretion of Bile and the Role of Bile Acids In Digestion". Colorado State Hypertextbook article on Bile. Archived from the ...
Bile salt malabsorption (primary bile acid diarrhea) where excessive bile acids in the colon produce a secretory diarrhea. ... Bile acid sequestrants such as cholestyramine can be effective in chronic diarrhea due to bile acid malabsorption. Therapeutic ... Standard home solutions such as salted rice water, salted yogurt drinks, vegetable and chicken soups with salt can be given. ... About 30% of patients with diarrhea-predominant IBS have bile acid malabsorption diagnosed with an abnormal SeHCAT test. ...
... the gene that codes for the bile salt export pump, or BSEP. Retention of bile salts within hepatocytes, which are the only cell ... The free or "unchaperoned" bile acids in bile of patients with MDR3 deficiency cause a cholangitis. Biochemically, this is of ... Biochemical markers include a normal GGT for PFIC-1 and -2, with a markedly elevated GGT for PFIC-3. Serum bile acid levels are ... Phosphatidylcholine normally chaperones bile acids, preventing damage to the biliary epithelium. ...
Gohyah Tea is good for bile, liver, dieuretic. Helpful to digestion; prevent from influenza, throat inflammation. Reduce ... When it is softened and reduced, it is crushed in a mortar with a few cloves of garlic, salt and a red or green pepper. It is ... Pantothenic acid (B5). 4%. 0.193 mg. Vitamin B6. 3%. 0.041 mg. ... boiled, drained, no salt. Nutritional value per 100 g (3.5 oz) ... In the Konkan region of Maharashtra, salt is added to finely chopped bitter gourd, known as karle (कारले) in Marathi, and then ...
Bile salt diarrhea can also be a side-effect of gallbladder removal. Bile acid sequestrants are the principal therapy for bile ... Bile acid sequestrants exchange anions such as chloride ions for bile acids. By doing so, they bind bile acids and sequester ... with appropriate intervals between dosing of the vitamins and bile acid sequestrants. In addition to bile acids, bile acid ... Thus, bile acid sequestrants, along with any bile acids bound to the drug, are excreted via the feces after passage through the ...
Bile Acids and Salts. 10. Liver Extracts. 11. Protein C Inhibitor. Interventional clinical trials:. ... is related to bile acid synthesis defect, congenital, 1 and congenital bile acid synthesis defect, and has symptoms including ... bile acid synthesis defect, congenital, 1 11.8. 2. congenital bile acid synthesis defect 11.6. ...
Enterohepatic circulation of bile salts in farnesoid X receptor-deficient mice: efficient intestinal bile salt absorption in ... Bile acids promote bile formation and facilitate dietary lipid absorption. Animal and human studies showing disturbed bile acid ... Bile acids are activating ligands of the farnesoid X receptor (FXR), a nuclear receptor with an established role in bile acid ... Animal and human studies employing bile acid sequestrants (bile acid binding agents), which interrupt the enterohepatic ...
... is a crystalline bile acid involved in the emulsification of fats. It occurs as a sodium salt in the bile of mammals. Its anion ... Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, ... Glycocholic acid is an acyl glycine and a bile acid-glycine conjugate. It is a secondary bile acid produced by the action of ... The major components of bile are cholic acid and chenodeoxycholic acid. In a first step the bile acids are converted to an acyl ...
Effect of bile acids on the proliferative activity and apoptosis of rat hepatocytes. Exp Toxicol Pathol. 2001; 53: 227-33.. * ... Hepatocyte transplantation in bile salt export pump-deficient mice: selective growth advantage of donor hepatocytes under bile ... Hepatocyte transplantation in bile salt export pump-deficient mice: selective growth advantage of donor hepatocytes under bile ... Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Biochemistry. 2005; 44: 12598-605.. *CrossRef, ...
T. Inamine, S. Higa, F. Noguchi et al., "Association of genes involved in bile acid synthesis with the progression of primary ... The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and ... C. Lang, Y. Meier, B. Stieger et al., "Mutations and polymorphisms in the bile salt export pump and the multidrug resistance ... P. L. M. Jansen, S. S. Strautnieks, E. Jacquemin et al., "Hepatocanalicular bile salt export pump deficiency in patients with ...
A Comparative Study of the Choleretic Effect of Bile Salts and Oleic Acid and Bile Salts(A Comparative Study of the Choleretic ... Effect of Bile Salts and Oleic Acid and Bile Salts*†)(A Comparative Study of the Choleretic Effect of Bile Salts and Oleic Acid ... A Comparative Study of the Choleretic Effect of Bile Salts and Oleic Acid and Bile Salts(A Comparative Study of the Choleretic ... Effect of Bile Salts and Oleic Acid and Bile Salts*†)(A Comparative Study of the Choleretic Effect of Bile Salts and Oleic Acid ...
Bile Salt-Fatty Acid Mixed Micelles as Nasal Absorption Promoters. III. Effects on Nasal Transport and Enzymatic Degradation of ... ester prodrugs were investigated in rats using the in situ nasal perfusion technique in the presence of bile salt-fatty acid ... Mixed micelles composed of 15 m M NaGC and 5 m M linoleic acid are incapable of incorporating these esters into the micellar ... To estimate the nasal epithelial membrane and cytoplasmic damaging effect caused by sodium glycocholate (NaGC)-linoleic acid ( ...
... to suppress the reabsorption of bile acids into the enterohepatic circulation and to enhance the excretion of bile acids in ... fecal bile acids and microflora was estimated in hypercholesterolemic rats. Anaerobic lactic acid bacteria decreased and ... Administration of milk and fermented milks produced from indigenous dadih lactic acid bacteria on serum lipids and bile acids, ... lactis IS-10285 significantly reduced serum total cholesterol, LDL cholesterol and total bile acids. Milk and fermented milks ...
... bile acid Certified Spiking Solution® of Ursodeoxycholic acid, Deoxycholic acid and Taurocholic acid sodium salt. ... Taurocholic acid sodium salt, T-110 500 ug/mL (as free sulfate) in Methanol Taurocholic acid (TCA) sodium salt, also known as ... Ursodeoxycholic acid, U-001 500 µg/mL in Methanol Ursodeoxycholic acid (UDCA) is a secondary bile acid that helps regulate ... Deoxycholic acid (DCA), also known as deoxycholate and cholanoic acid is a secondary bile acid that aids in the absorption of ...
Bile Salts, and Acids flashcards from Annette Liem ... bile acids) and 50% unprotonated (bile salts). -OH groups are ... albumin binds and transports bile salts in blood. -hepatocytes take bile salts from blood with an isoform of Na+-bile ... but sterol nucleus is eliminated by conversion to bile acids and bile salts. -small percentage of cholesterol in feces or bile ... before bile acids leave the liver. -amide bond forms between carboxyl group of bile acid and amino group of glycine (carboxyl) ...
bile* is a greenish-yellow fluid produced by the liver [1], and passing from there into the duodenum [2]; it has a number of ... Bile, or gall, is composed of water, bile acids and their salts, bile pigments, cholesterol, fatty acids, and inorganic salts. ... bile pigments, and electrolytes (minerals).. Bile acids and bile salts. The function of these remarkable molecules is ... by increasing the bile acid/cholesterol ratio of bile. This is achieved simply by taking synthetic bile acids by mouth. ...
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds ... WP1788: Bile acid and bile salt metabolism. WP1828: Hexose transport. WP1847: Metabolism of amino acids and derivatives. WP1877 ... BILE SALTS MIXTURE (Equivalent to Bile Salt No. 3). 100 gm. 28-048. M96 may be involved in the activation of MT ( ... bile salts and organic acids, metal ions and amine compounds. pathways : Transport of glucose and other sugars, bile salts and ...
Finding natural treatments for bile acid diarrhea can be difficult. But searching for root causes of loose, watery and green ... Natural Treatments For Bile Acid Diarrhea (aka Bile Salt Diarrhea). CLICK HERE TO JOIN OUR NEXT SMALL GROUP TRAINING USING THE ... Natural Treatments For Bile Acid Diarrhea (The Holistic Way). The key to treating bile acid diarrhea effectively is treating ... If the artichoke binds to the bile acids, but my problem is from too little bile acid, would this exacerbate my symptoms? Do ...
... function of xenoperfused livers and compatibility with human bile salts and porcine livers. ... Bile acids in xenogeneic ex-vivo liver perfusion: ... bile acid from serum is similar to bile acid excretion in bile ... human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients sera after 1 hr of perfusion, ... and glyco-3alpha-hydroxy-6-oxo-5beta-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were ...
Moreover, bile salt hydrolase (BSH) activity was evaluated both qualitatively and quantitatively. The results showed that none ... but were more responsive to oxidative and bile stress. The bacterial isolates also expressed high amounts of BSH, ranging from ... EIGHT lactic acid bacterial (LAB) isolates were obtained from food and non-food sources and identified by 16S rRNA gene ... "Probiotic Properties and Bile Salt Hydrolase Activity of Some Isolated Lactic Acid Bacteria". Egyptian Journal of Microbiology ...
... binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt ... binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt ... binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt ... binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt ...
Throwing up bile, a yellow or greenish liquid, can happen for many reasons. Some of the causes may be serious and require ... salts. *bile acids. *bilirubin. *water. *certain metals. Causes of vomiting bile. Vomiting bile can occur whenever a person ... Bile reflux is not the same as acid reflux, though their symptoms are similar. Bile reflux occurs when bile backs up into a ... In cases of bile reflux, a doctor may prescribe medication to control the reflux. Two common types include:. *bile acid ...
Any member of a group of hydroxy-5β-cholanic acids occuring in bile, where they are present as the sodium salts of their amides ... bile acid (CHEBI:3098) is a bile acids (CHEBI:138366) bile acid (CHEBI:3098) is a hydroxy-5β-cholanic acid (CHEBI:24663) ... bile acid (CHEBI:3098). lithocholic acid (CHEBI:16325) is a bile acid (CHEBI:3098). Meliantriol (CHEBI:80723) is a bile acid ( ... bile acid (CHEBI:3098). Squalamine (CHEBI:80765) is a bile acid (CHEBI:3098). ursocholic acid (CHEBI:81240) is a bile acid ( ...
Bile is a fluid that is made and released by the liver and stored in the gallbladder. ... Bile acids (also called bile salts). *Bilirubin (a breakdown product or red blood cells) ... Bile helps with digestion. It breaks down fats into fatty acids, which can be taken into the body by the digestive tract. ... Bile is a fluid that is made and released by the liver and stored in the gallbladder. ...
Bile Acids and Salts. LinkOut - more resources. Full Text Sources. *Taylor & Francis ... Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate ... Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is ... Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation.. ...
The Effect of VSL#3 Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease. This study ... Change of the spectrum of bile acids in stools and plasma [ Time Frame: Baseline and 6 weeks (plus or minus 5 days). ]. *Change ... Bile acids (BA) play an important role in the gastrointestinal tract - besides facilitating fat (and protein) digestion and ... Alteration in the rate of bile acid synthesis [ Time Frame: Baseline and 6 weeks (plus or minus 5 days) ]. Will be assessed as ...
Bile Acids and Salts. Anticholesteremic Agents. Hypolipidemic Agents. Antimetabolites. Molecular Mechanisms of Pharmacological ... bowel bile acid will be treated with colesevelam to determine if stool frequency and consistency improves via fecal bile acids ... Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption. The safety and ... Chronic Diarrhea Irritable Bowel Syndrome With Diarrhea Bile Acid Malabsorption Drug: Colesevelam Other: Placebo Phase 2 ...
Primary Bile Acid Malabsorption Secondary Bile Acid Malabsorption Chronic Diarrhoea Drug: Obeticholic acid Phase 2 ... Primary bile acid malabsorption. Secondary bile acid malabsorption. Chronic diarrhoea. Obeticholic acid. SeHCAT. FXR. FGF19. ... in patients with bile acid diarrhoea. OCA is a semisynthetic bile acid, also known as 6αethylchenodeoxycholic acid or INT747, ... Serum total bile acids. [ Time Frame: 15 days. ]. Dynamic changes of total bile acids over 6 hour period following OCA ...
Bile Duct Diseases. Biliary Tract Diseases. Pathologic Processes. Vancomycin. Bile Acids and Salts. Anti-Bacterial Agents. Anti ... Bile acids will be measured on each sample and the average composition of primary to secondary bile acids over the 5 day period ... A Pilot Study to Characterize Bile Acid Metabolism and Dysbiosis in Primary Sclerosing Cholangitis. The safety and scientific ... Bile acids (BAs) represent a unique mechanism of communication between the host and intestinal microbiome and the liver. ...
  • In lipid-lowering trials, bile acid sequestrants, such as colesevelam hydrochloride, colestyramine (cholestyramine) and colestilan (colestimide), have also been shown to lower plasma glucose and glycosylated haemoglobin levels, suggesting the utility of these agents as a potential therapy for type 2 diabetes. (springer.com)
  • This condition of bile acid malabsorption occurs after surgery to the ileum, in Crohn's disease, with a number of other gastrointestinal causes, or is commonly a primary, idiopathic condition. (wikipedia.org)
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