Genetic defects in hepatocanalicular transport.

Bile is made as the result of active transport of its constituents into the biliary space. Most of this transport occurs across the canalicular membrane, with a further contribution from cholangiocytes. Water moves passively into bile. The major substrates that are transported out of hepatocytes are bile acids, phospholipids, cholesterol, and bilirubin. With the exception of cholesterol, each of these major substrates is now recognized to have its own transport mechanism. In the case of bile acids and phospholipids, the transporters appear to be specific, though the bilirubin transporter is multispecific. Isolated autosomal recessive defects in all three of these transporters have now been identified and have helped to confirm the physiologic role of these proteins. In addition, a secondary defect in bile acid transport has been identified that appears to be due to an abnormality in plasma membrane aminophospholipid distribution.