Bile acid metabolism Genetic		Much has been learned in the past 10-15 years about the physiology of the hepatocyte. There are specific transporter proteins that are responsible for the uptake and excretion functions of the hepatocyte. Uptake of various substances into the hepatocyte from sinusoidal blood occurs at the basolateral surface of the hepatocyte. Three uptake transporters have been identified: NTCP - the Na/taurocholate cotransporting polypeptide. This is the primary mediator of uptake of conjugated bile acids. OATPs - organic anion transporting polypeptide family. This group of proteins are responsible for the bidirectional transport of many substances including bilirubin, bile acids, drugs and hormones. MRP3 - multidrug resistance protein 3. This protein transports bile acids and conjugated bilirubin out of the hepatocyte into the sinusoids. This becomes important in cholestasis where there is impaired excretion of the substances into the bile and allows their passage out of the liver cell into the sinusoids, leading to their increased serum levels. Several transporters active at the apical surface of the hepatocyte involved in excretion have also been identified: BSEP - the bile salt export pump. This is the primary transporter responsible for bile acid export into the bile. It uses ATP to transport bile acids against the very high concentration gradient found at the canalicular membrane. The concentration of bile acids in bile is almost 1000 times that in the hepatocyte. MRP2 - multidrug resistance protein 2. This protein is responsible for most of the BAIF across the canalicular membrane. MRP2 transports glutathione and conjugates of drugs, toxins, bile acids and bilirubin into bile. MDR3 - multidrug resistance protein 3. Same name, different protein. This transporter is responsible for secretion of phospholipids into bile. FIC1 - familial intrahepatic cholestasis 1. This transporter is not well understood, but may be responsible for the transport of highly hydrophobic bile acids into bile. ABCG5 and ABCG8 - these 2 ATP binding cassette proteins are the primary biliary cholesterol transporters. Cholangiocytes, which line the bile ducts, secrete water and chloride into the bile. The transporter responsible for this is CFTR - the cystic fibrosis transmembrane regulator. Return to top of page