Reaction: Defective ABCB4 does not transport PC from plasma membrane to extracellular region
- in pathway: Defective ABCB4 causes PFIC3, ICP3 and GBD1
Multidrug resistance protein 3 (ATP-binding cassette sub-family B member 4, ABCB4 aka MDR3) mediates the ATP-dependent export of organic anions, phospholipids and drugs from hepatocytes into the canalicular lumen in the presence of bile salts, especially the export of phospholipids such as phosphatidylcholine (PC). Biliary phospholipids associate with bile salts and cholesterol in mixed micelles, thereby reducing the detergent activity and cytotoxicity of bile salts and preventing cholesterol crystallisation. Thus, ABCB4 plays a crucial role in bile formation and lipid homeostasis.
Defects in ABCB4 result in a wide spectrum of cholestasis phenotypes, from progressive familial intrahepatic cholestasis 3 (PFIC3; MIM:602347), intrahepatic cholestasis of pregnancy 3 (ICP3; MIM:614972) to gallbladder disease 1 (GBD1; MIM:600803). Mutations causing PFIC3 include R957*, Y403H and V571Dfs*16 (de Vree et al. 1998, Degiorgio et al. 2007, Jacquemin et al. 1999). Mutations causing ICP3 include A546D, R144* and R590Q (Dixon et al. 2000, Bacq et al. 2009, Ziol et al. 2008). Mutations causing GBD1 include T175V, P1161S and R545G (Rosmorduc et al. 2001, Ziol et al. 2008).
Defects in ABCB4 result in a wide spectrum of cholestasis phenotypes, from progressive familial intrahepatic cholestasis 3 (PFIC3; MIM:602347), intrahepatic cholestasis of pregnancy 3 (ICP3; MIM:614972) to gallbladder disease 1 (GBD1; MIM:600803). Mutations causing PFIC3 include R957*, Y403H and V571Dfs*16 (de Vree et al. 1998, Degiorgio et al. 2007, Jacquemin et al. 1999). Mutations causing ICP3 include A546D, R144* and R590Q (Dixon et al. 2000, Bacq et al. 2009, Ziol et al. 2008). Mutations causing GBD1 include T175V, P1161S and R545G (Rosmorduc et al. 2001, Ziol et al. 2008).
Reaction - small molecule participants:
H2O [cytosol]
PC [plasma membrane]
ATP [cytosol]
Reactome.org reaction link: R-HSA-5678749
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Reaction input - small molecules:
water
1,2-diacyl-sn-glycero-3-phosphocholine
ATP(4-)
Reaction output - small molecules:
Reactome.org link: R-HSA-5678749