Bile Acid Transporters: Structure, Function, Regulation and Pathophysiological Implications

Alrefai, Waddah A.; Gill, Ravinder K.

doi:10.1007/s11095-007-9289-1

Cited by 500Drug Transport and Resistance MechanismsCholesterol and Lipid MetabolismPharmacogenetics and Drug Metabolism

Bile Acid Transporters: Structure, Function, Regulation and Pathophysiological Implications

Alrefai, Waddah A., Gill, Ravinder K.·2007·Pharmaceutical Research

DOI 10.1007/s11095-007-9289-1

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Abstract

Specific transporters expressed in the liver and the intestine, play a critical role in driving the enterohepatic circulation of bile acids. By preserving a circulating pool of bile acids, an important factor influencing bile flow, these transporters are involved in maintaining bile acid and cholesterol homeostasis. Enterohepatic circulation of bile acids is fundamentally composed of two major processes: secretion from the liver and absorption from the intestine. In the hepatocytes, the vectorial transport of bile acids from blood to bile is ensured by Na+ taurocholate co-transporting peptide (NTCP) and organic anion transport polypeptides (OATPs). After binding to a cytosolic bile acid binding protein, bile acids are secreted into the canaliculus via ATP-dependent bile salt excretory pump (BSEP) and multi drug resistant proteins (MRPs). Bile acids are then delivered to the intestinal lumen through bile ducts where they emulsify dietary lipids and cholesterol to facilitate their absorption. Intestinal epithelial cells reabsorb the majority of the secreted bile acids through the apical sodium dependent bile acid transporter (ASBT) and sodium independent organic anion transporting peptide (OATPs). Cytosolic ileal bile acid binding protein (IBABP) mediates the transcellular movement of bile acids to the basolateral membrane across which they exit the cells via organic solute transporters (OST). An essential role of bile acid transporters is evident from the pathology associated with their genetic disruption or dysregulation of their function. Malfunctioning of hepatic and intestinal bile acid transporters is implicated in the pathophysiology of cholestatic liver disease and the depletion of circulating pool of bile acids, respectively. Extensive efforts have been recently made to enhance our understanding of the structure, function and regulation of the bile acid transporters and exploring new potential therapeutics to treat bile acid or cholesterol related diseases. This review will highlight current knowledge about structure, function and molecular characterization of bile acid transporters and discuss the implications of their defects in various hepatic and intestinal disorders.

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ASBT plays a key role in the enterohepatic recycling of bile acids and indirectly contributes to cholesterol homeostasis.
“Recently, it was found that ASBT plays a key role in the enterohepatic recycling of BAs and indirectly contributes to cholesterol homoeostasis (26).”
From Resveratrol Attenuates Trimethylamine- N -Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota (2016) · cites this paper as [26]
The increase in BSH activity might result in a decrease in ileal bile acid content, because ileal bile acid transporters prefer conjugated bile acids to unconjugated bile acids.
“This might also result in the decrease in ileal BA content, because the ileal BA transporters prefer conjugated BAs to unconjugated BAs (26).”
From Resveratrol Attenuates Trimethylamine- N -Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota (2016) · cites this paper as [26]

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Authors: Alrefai, W. A., & Gill, R. K.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Alrefai, Waddah A.
ORCID: Alrefai, Waddah A.
Gill, Ravinder K.
Venue: Pharmaceutical Research
Publisher: Springer Science and Business Media LLC
Published: 2007-04-03
Volume: 24
Issue: 10
Pages: 1803-1823
ISSN: 0724-8741 (ISSN-L)
1573-904X
DOI: 10.1007/s11095-007-9289-1
OpenAlex: W2071450296
Cited by: 500
References: 215
Citations by year: 2026: 20 · 2025: 19 · 2024: 24 · 2023: 21 · 2022: 33 · 2021: 27 · 2020: 23 · 2019: 34 · 2018: 33 · 2017: 24 · 2016: 27 · 2015: 22 · 2014: 28 · 2013: 29 · 2012: 27
FWCI: 2.75
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Pharmaceutical Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK 71596)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: bile acid transporters, enterohepatic circulation, bile acid homeostasis, cholesterol homeostasis, normal tissue complication probability, organic anion transporting polypeptides, bile salt export pump, MRP, ASBT, ileal bile acid binding protein, cholestatic liver disease
MeSH terms: Animals, Bile Acids and Salts, Bile Canaliculi, Bile Ducts, Carrier Proteins, Cholestasis, Enterohepatic Circulation, Epithelial Cells, Humans, Intestinal Mucosa, Kidney Tubules, Proximal, Liver, Membrane Glycoproteins, Protein Conformation, Cell Polarity, ATP-Binding Cassette Transporters, Enterocytes, Hepatocytes, Symporters, Organic Anion Transporters, Sodium-Independent, Organic Anion Transporters, Sodium-Dependent

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Bile Acid Transporters: Structure, Function, Regulation and Pathophysiological Implications

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