The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
Bruno Stieger - One of the best experts on this subject based on the ideXlab platform.
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Bile Salt Transporters
Drug Transporters: Molecular Characterization and Role in Drug Disposition: Second Edition, 2014Co-Authors: Jyrki J Eloranta, Bruno Stieger, Gerd-achim Kullak-ublickAbstract:Bile salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile salt uptake is mediated predominantly by the Na+-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na+-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile salt–binding proteins) to the canalicular membrane, monoanionic Bile salts are secreted into Bile canaliculi by the Bile salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile salts are secreted into Bile by the multidrugresistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile salt transporters have been recognized as important causes for various cholestatic liver diseases
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Drug Transporters - Bile Salt Transporters
Annual review of physiology, 2002Co-Authors: Peter J. Meier, Bruno StiegerAbstract:Bile salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile salt uptake is mediated predominantly by the Na(+)-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na(+)-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile salt-binding proteins) to the canalicular membrane, monoanionic Bile salts are secreted into Bile canaliculi by the Bile salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile salts are secreted into Bile by the multidrug-resistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile salt transporters have been recognized as important causes for various cholestatic liver diseases.
Gerd-achim Kullak-ublick - One of the best experts on this subject based on the ideXlab platform.
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Bile Salt Transporters
Drug Transporters: Molecular Characterization and Role in Drug Disposition: Second Edition, 2014Co-Authors: Jyrki J Eloranta, Bruno Stieger, Gerd-achim Kullak-ublickAbstract:Bile salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile salt uptake is mediated predominantly by the Na+-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na+-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile salt–binding proteins) to the canalicular membrane, monoanionic Bile salts are secreted into Bile canaliculi by the Bile salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile salts are secreted into Bile by the multidrugresistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile salt transporters have been recognized as important causes for various cholestatic liver diseases
Alan F. Hofmann - One of the best experts on this subject based on the ideXlab platform.
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the enterohepatic circulation of Bile acids in mammals form and functions
Frontiers in Bioscience, 2009Co-Authors: Alan F. HofmannAbstract:The features of the enterohepatic circulation of Bile acids in mammals are reviewed. Inputs into the circulating Bile acids are primary Bile acids synthesized from cholesterol in the hepatocyte and secondary Bile acids formed by bacterial modification of primary Bile acids in the distal intestine. Intestinal conservation of Bile acids generates pools of individual Bile acids whose relative sizes determine biliary Bile acid composition. Efficient hepatic clearance results in low plasma Bile acid levels, and virtually no renal excretion. Methods for characterizing the enterohepatic circulation are summarized. Bile acids have numerous physiological functions in the liver, biliary tract, and intestine resulting from their signaling and physicochemical properties.
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Bile acids chemistry pathochemistry biology pathobiology and therapeutics
Cellular and Molecular Life Sciences, 2008Co-Authors: Alan F. Hofmann, Lee R HageyAbstract:Bile acids and Bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of Bile acids and Bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of Bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of Bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of Bile, or to decrease the cytotoxicity of retained Bile acids in cholestatic liver disease.
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Human cecal Bile acids: concentration and spectrum
American Journal of Physiology-gastrointestinal and Liver Physiology, 2007Co-Authors: James P. Hamilton, Lee R Hagey, Jean-pierre Raufman, Susan Hogan, Terrance L. Griffin, Christine A. Packard, Dale A. Chatfield, Joseph H. Steinbach, Alan F. HofmannAbstract:To obtain information on the concentration and spectrum of Bile acids in human cecal content, samples were obtained from 19 persons who had died an unnatural death from causes such as trauma, homicide, suicide, or drug overdose. Bile acid concentration was measured via an enzymatic assay for 3α-hydroxy Bile acids; Bile acid classes were determined by electrospray ionization mass spectrometry and individual Bile acids by gas chromatography mass spectrometry and liquid chromatography mass spectrometry. The 3α-hydroxy Bile acid concentration (μmol Bile acid/ml cecal content) was 0.4 ± 0.2 mM (mean ± SD); the total 3-hydroxy Bile acid concentration was 0.6 ± 0.3 mM. The aqueous concentration of Bile acids (supernatant after centrifugation) was identical, indicating that most Bile acids were in solution. By liquid chromatography mass spectrometry, Bile acids were mostly in unconjugated form (90 ± 9%, mean ± SD); sulfated, nonamidated Bile acids were 7 ± 5%, and nonsulfated amidated Bile acids (glycine or tauri...
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the continuing importance of Bile acids in liver and intestinal disease
JAMA Internal Medicine, 1999Co-Authors: Alan F. HofmannAbstract:Bile acids, the water-soluble, amphipathic end products of cholesterol metabolism, are involved in liver, biliary, and intestinal disease. Formed in the liver, Bile acids are absorbed actively from the small intestine, with each molecule undergoing multiple enterohepatic circulations before being excreted. After their synthesis from cholesterol, Bile acids are conjugated with glycine or taurine, a process that makes them impermeable to cell membranes and permits high concentrations to persist in Bile and intestinal content. The relation between the chemical structure and the multiple physiological functions of Bile acids is reviewed. Bile acids induce biliary lipid secretion and solubilize cholesterol in Bile, promoting its elimination. In the small intestine, Bile acids solubilize dietary lipids promoting their absorption. Bile acids are cytotoxic when present in abnormally high concentrations. This may occur intracellularly, as occurs in the hepatocyte in cholestasis, or extracellulary, as occurs in the colon in patients with Bile acid malabsorption. Disturbances in Bile acid metabolism can be caused by (1) defective biosynthesis from cholesterol or defective conjugation, (2) defective membrane transport in the hepatocyte or ileal enterocyte, (3) defective transport between organs or biliary diversion, and (4) increased bacterial degradation during enterohepatic cycling. Bile acid therapy involves Bile acid replacement in deficiency states or Bile acid displacement by ursodeoxycholic acid, a noncytotoxic Bile acid. In cholestatic liver disease, administration of ursodeoxycholic acid decreases hepatocyte injury by retained Bile acids, improving liver tests, and slowing disease progression. Bile acid malabsorption may lead to high concentrations of Bile acids in the colon and impaired colonic mucosal function; Bile acid sequestrants provide symptomatic benefit for diarrhea. A knowledge of Bile acid physiology and the perturbations of Bile acid metabolism in liver and digestive disease should be useful for the internist.
Jyrki J Eloranta - One of the best experts on this subject based on the ideXlab platform.
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Bile Salt Transporters
Drug Transporters: Molecular Characterization and Role in Drug Disposition: Second Edition, 2014Co-Authors: Jyrki J Eloranta, Bruno Stieger, Gerd-achim Kullak-ublickAbstract:Bile salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile salt uptake is mediated predominantly by the Na+-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na+-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile salt–binding proteins) to the canalicular membrane, monoanionic Bile salts are secreted into Bile canaliculi by the Bile salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile salts are secreted into Bile by the multidrugresistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile salt transporters have been recognized as important causes for various cholestatic liver diseases
Peter J. Meier - One of the best experts on this subject based on the ideXlab platform.
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Drug Transporters - Bile Salt Transporters
Annual review of physiology, 2002Co-Authors: Peter J. Meier, Bruno StiegerAbstract:Bile salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile salt uptake is mediated predominantly by the Na(+)-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na(+)-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile salt-binding proteins) to the canalicular membrane, monoanionic Bile salts are secreted into Bile canaliculi by the Bile salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile salts are secreted into Bile by the multidrug-resistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile salt transporters have been recognized as important causes for various cholestatic liver diseases.