Targeting the Four Pillars of Enterohepatic Bile Salt Cycling; Lessons From Genetics and Pharmacology.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Roni F KunstStan F J van de Graaf

Abstract

Bile salts play a pivotal role in lipid homeostasis, are sensed by specialized receptors, and have been implicated in various disorders affecting the gut or liver. They may play a role either as culprit or as potential panacea. Four very efficient transporters mediate most of the hepatic and intestinal bile salt uptake and efflux, and are each essential for the efficient enterohepatic circulation of bile salts. Starting from the intestinal lumen, conjugated bile salts cross the otherwise impermeable lipid bilayer of (primarily terminal ileal) enterocytes through the apical sodium-dependent bile acid transporter (gene SLC10A2) and leave the enterocyte through the basolateral heteromeric organic solute transporter, which consists of an alpha and beta subunit (encoded by SLC51A and SLC51B). The Na+ -taurocholate cotransporting polypeptide (gene SLC10A1) efficiently clears the portal circulation of bile salts, and the apical bile salt export pump (gene ABCB11) pumps the bile salts out of the hepatocyte into primary bile, against a very steep concentration gradient. Recently, individuals lacking either functional Na+ -taurocholate cotransporting polypeptide or organic solute transporter have been described, completing the quartet of...Continue Reading

References

Jul 7, 1973·Lancet·G R Thompson, A M Gotto
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·W WangN Ballatori
Jun 24, 2003·The Journal of Biological Chemistry·Paul A DawsonJohn S Parks
Sep 15, 2005·Biochemistry·Ping LamVictor Ling
Feb 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anuradha RaoPaul A Dawson
May 24, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Nazzareno BallatoriChristine L Hammond
Aug 2, 2008·Nature Reviews. Drug Discovery·Charles ThomasKristina Schoonjans
Aug 4, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Renxue WangVictor Ling
Nov 11, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Carol J SorokaJames L Boyer
Jul 2, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Carol J SorokaJames L Boyer
Sep 22, 2011·American Journal of Physiology. Endocrinology and Metabolism·Lihong ChenBronislava Gedulin
May 24, 2012·The Journal of Biological Chemistry·Yuanyuan ZhangJohn D Schuetz
May 29, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Frédéric M VazRonald J A Wanders
Jul 31, 2014·Pharmacological Reviews·Tiangang Li, John Y L Chiang
Nov 25, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang PengYiming Wang
Feb 3, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Davor SlijepcevicStan F J van de Graaf
Feb 27, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Emmanuel GonzalesEmmanuel Jacquemin
Jul 15, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alexander G MiethkeKenneth D R Setchell
Sep 7, 2016·Journal of Hepatology·Claudia D FuchsMichael Trauner
Jan 18, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·O Chávez-TalaveraF Pattou
May 26, 2017·Clinical Pharmacology and Therapeutics·A BlankW E Haefeli
Sep 13, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mutaz SultanPaul A Dawson
Nov 2, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jillian L EllisChunyue Yin
Mar 25, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Davor SlijepcevicStan F J van de Graaf
Apr 21, 2018·Cellular and Molecular Gastroenterology and Hepatology·Sandra M W van de WielStan F J van de Graaf
Jun 23, 2018·Cellular and Molecular Gastroenterology and Hepatology·Courtney B FerrebeePaul A Dawson
Jul 27, 2018·The Lancet. Gastroenterology & Hepatology·Reinout L P Roscam AbbingStan F J van de Graaf
Aug 24, 2018·Clinical Pharmacology and Therapeutics·J Gerry KennaUNKNOWN International Transporter Consortium
Sep 30, 2018·Clinics in Liver Disease·Laura N Bull, Richard J Thompson
Oct 6, 2018·Hepatology Communications·Benjamin L ShneiderUNKNOWN Childhood Liver Disease Research Network

❮ Previous
Next ❯

Citations

May 2, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Monique D AppelmanStan F J van de Graaf
Aug 17, 2021·Frontiers in Nutrition·Pan HuangAihua Gong
Sep 24, 2021·Alimentary Pharmacology & Therapeutics·Benedikt SimbrunnerThomas Reiberger

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.