Core Concepts: Bilirubin Metabolism

Abstract

Bilirubin is formed in the reticuloendothelial system as the end product of heme catabolism through a series of oxidation-reduction reactions. The predominant bilirubin isomer in humans is IX-alpha (Z,Z), which, because of its lipophilic nature, can cross phospholipid membranes. In fetal life, this characteristic permits passage of bilirubin through the placenta into the maternal organism for excretion. Postpartum, this same characteristic enables passage of bilirubin across the blood-brain barrier, which is why clinicians worry about jaundice in newborns. Bilirubin is transported in serum bound to albumin. When the bilirubin-albumin complex reaches the liver, bilirubin is transferred into the hepatocytes, where it is bound to ligandin. The next step, which occurs inside the hepatocyte, is binding of bilirubin to glucuronic acid (conjugation) through the enzyme uridine diphosphate glucuronyl transferase (UDPGT). Both ligandin and UDPGT have very low concentrations and activities in the fetus, but activity increases greatly after birth. However, during the time required to increase these enzyme activities, bilirubin accumulates. An important factor in this process is increased bilirubin production through the breakdown of fetal erythrocytes. Once conjugated in the liver, bilirubin is excreted into the bile and transported through the gut with food and further broken down, contributing to the color of stool. Deconjugation and reabsorption of bilirubin can occur in the bowel, a process known as enterohepatic circulation. Increased enterohepatic circulation is believed to contribute to prolonged jaundice in some newborns and may be partially responsible for human milk-associated jaundice. Some of the steps in bilirubin metabolism can be influenced by drugs or feeding.