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ABCB4/MDR3 in health and disease – at the crossroads of biochemistry and medicine

Authors :
Lutz Schmitt
Tim Kroll
Martin Prescher
Source :
Biological Chemistry. 400:1245-1259
Publication Year :
2019
Publisher :
Walter de Gruyter GmbH, 2019.

Abstract

Several ABC transporters of the human liver are responsible for the secretion of bile salts, lipids and cholesterol. Their interplay protects the biliary tree from the harsh detergent activity of bile salts. Among these transporters, ABCB4 is essential for the translocation of phosphatidylcholine (PC) lipids from the inner to the outer leaflet of the canalicular membrane of hepatocytes. ABCB4 deficiency can result in altered PC to bile salt ratios, which led to intrahepatic cholestasis of pregnancy, low phospholipid associated cholelithiasis, drug induced liver injury or even progressive familial intrahepatic cholestasis type 3. Although PC lipids only account for 30–40% of the lipids in the canalicular membrane, 95% of all phospholipids in bile are PC lipids. We discuss this discrepancy in the light of PC synthesis and bile salts favoring certain lipids. Nevertheless, the in vivo extraction of PC lipids from the outer leaflet of the canalicular membrane by bile salts should be considered as a separate step in bile formation. Therefore, methods to characterize disease causing ABCB4 mutations should be considered carefully, but such an analysis represents a crucial point in understanding the currently unknown transport mechanism of this ABC transporter.

Details

ISSN :
14374315 and 14316730
Volume :
400
Database :
OpenAIRE
Journal :
Biological Chemistry
Accession number :
edsair.doi.dedup.....b439808ae38ddf035b29830bb74bc134
Full Text :
https://doi.org/10.1515/hsz-2018-0441