Abstract
This is a brief review of the regulatory mechanisms and abnormalities of bilirubin transport and metabolism in hepatocytes. The induction and suppression of hepatocyte transporters by nuclear receptors are outlined. A linkage has been recognized between UGT1A1 polymorphism (UGT1A1*6) that causes Gilbert's syndrome and UGT1A polymorphisms (UGT1A6*2 and UGT1A7*3) that cause disturbance of drug glucuronide conjugation and high incidence of lung cancer. Defects of MRP2 in the Dubin-Johnson syndrome and of GST-alpha in the Rotor's syndrome also indicate disturbance in the metabolism of anionic drugs. Hepatic enzymes and transporters are also reduced in acquired hepatobiliary disorders that cause jaundice; thus, occurrence of abnormalities in the metabolism of anionic drugs should be also taken into consideration in acquired hepatobiliary diseases with jaundice.
