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ABCB4/MDR3 in health and disease – at the crossroads of biochemistry and medicine
- 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.
- Subjects :
- 0301 basic medicine
ATP Binding Cassette Transporter, Subfamily B
Clinical Biochemistry
ATP-binding cassette transporter
Cholestasis, Intrahepatic
digestive system
Biochemistry
Bile Acids and Salts
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Phosphatidylcholine
medicine
Animals
Humans
Secretion
Molecular Biology
Chemistry
Cholesterol
Progressive familial intrahepatic cholestasis
Biological Transport
Transporter
ABCB4
medicine.disease
030104 developmental biology
Mutation
Hepatocytes
Phosphatidylcholines
lipids (amino acids, peptides, and proteins)
030211 gastroenterology & hepatology
Cholestasis of pregnancy
Subjects
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