Bilirubin metabolism: Applied physiology

Bilirubin is the breakdown product of the haem moiety of haemoglobin and other haemoproteins. Because of internal hydrogen bonding, bilirubin is water-insoluble and requires enzyme-mediated glucuronidation in the liver for biliary excretion. In normal circumstances, plasma bilirubin is mostly unconjugated and is tightly bound to circulating albumin. It is taken up by hepatocytes by facilitated diffusion, stored in hepatocytes bound to glutathione-S-transferases and conjugated to glucuronides by microsomal UGT1A1. Bilirubin glucuronides are actively transported into the bile canaliculi by the ATP-utilizing pump MRP2. Bilirubin is degraded in the intestine by bacteria into urobilinogens, which are partly excreted in the urine. Increased production, reduced uptake and low glucuronidation capacity can increase plasma unconjugated bilirubin levels. In cases of inherited or acquired deficiencies of bilirubin storage or excretion, both conjugated and unconjugated bilirubin accumulate in the plasma. Conjugated bilirubin is less tightly bound to albumin and is excreted in the urine. The capacities of the various steps of bilirubin throughput are finely balanced, and the expression of the gene products mediating these steps is coordinated by nuclear receptors.