Genetic defects in hepatobiliary transport

Biochim Biophys Acta. 2002 Mar 16;1586(2):129-45. doi: 10.1016/s0925-4439(01)00103-x.

Abstract

Bile formation, the exocrine function of the liver, represents a process that is unique to the hepatocyte as a polarized epithelial cell. The generation of bile flow is an osmotic process and largely depends on solute secretion by primary active transporters in the apical membrane of the hepatocyte. In recent years an impressive progress has been made in the discovery of these proteins, most of which belong to the family of ABC transporters. The number of identified ABC transporter genes has been exponentially increasing and the mammalian subfamily now counts at least 52. This development has been of crucial importance for the elucidation of the mechanism of bile formation, and it is therefore not surprising that the development in this field has run in parallel with the discovery of the ABC genes. With the identification of these transporter genes, the background of a number of inherited diseases, which are caused by mutations in these solute pumps, has now been elucidated. We now know that at least six primary active transporters are involved in canalicular secretion of biliary components (MDR1, MDR3, BSEP, MRP2, BCRP and FIC1). Four of these transporter genes are associated with inherited diseases. In this minireview we will shortly describe our present understanding of bile formation and the associated inherited defects.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Bile Acids and Salts / metabolism
  • Bile Canaliculi / metabolism*
  • Cholestasis, Extrahepatic / complications
  • Cholestasis, Extrahepatic / genetics
  • Cholestasis, Extrahepatic / metabolism
  • Cholestasis, Intrahepatic / complications
  • Cholestasis, Intrahepatic / genetics
  • Cholestasis, Intrahepatic / metabolism
  • Cholesterol / blood
  • Female
  • Humans
  • Jaundice, Chronic Idiopathic / genetics
  • Jaundice, Chronic Idiopathic / metabolism
  • Lipid Metabolism
  • Mutation
  • Pregnancy
  • Pregnancy Complications / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Bile Acids and Salts
  • Cholesterol