Bile salt export pump

Definition:

Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner. Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts. Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion.

References:

[1]. Liang Wang, et al. Cryo-EM structure of human bile salts exporter ABCB11. Cell Res. 2020 Jul;30(7):623-625. [Content Brief]

[2]. Soichiro Matsushima, et al. Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol. 2008 May;73(5):1474-83. [Content Brief]

[3]. Masaru Hirano, et al. Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther. 2005 Aug;314(2):876-82. [Content Brief]

[4]. Hisamitsu Hayashi, et al. Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hepatology. 2005 Apr;41(4):916-24. [Content Brief]

[5]. Coen C Paulusma, et al. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem. 2009 Apr 10;284(15):9947-54. [Content Brief]

[6]. Hikaru Yabuuchi, et al. Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins. Biopharm Drug Dispos. 2008 Nov;29(8):441-8. [Content Brief]

[7]. Kazuo Imagawa, et al. Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis. J Hum Genet. 2018 May;63(5):569-577. [Content Brief]

[8]. Richard H Ho, et al. Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability. Pharmacogenet Genomics. 2010 Jan;20(1):45-57. [Content Brief]

[9]. Hisamitsu Hayashi, et al. AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function. Hepatology. 2012 Jun;55(6):1889-900. [Content Brief]

[10]. Takuya Kato, et al. Short- and medium-chain fatty acids enhance the cell surface expression and transport capacity of the bile salt export pump (BSEP/ABCB11). Biochim Biophys Acta. 2010 Sep;1801(9):1005-12. [Content Brief]

[11]. Hisamitsu Hayashi, et al. Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep. Biochim Biophys Acta. 2005 Dec 30;1738(1-3):54-62. [Content Brief]

[12]. Christelle Guyot, et al. Differential effects of membrane cholesterol content on the transport activity of multidrug resistance-associated protein 2 (ABCC2) and of the bile salt export pump (ABCB11). Mol Pharmacol. 2014 Jun;85(6):909-20. [Content Brief]

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