Metabolism - Conjugation
Bilirubin metabolism
Conjugation
Bilirubin excretion into bile demands conversion of the lipid-soluble unconjugated bilirubin to a more water-soluble form. In the normal adult, conjugation with glucuronide accounts for the disposal of 90% of all bilirubin. Ligandin may assist in delivering bilirubin to the endoplasmic reticulum (ER), the site of conjugation. Within the ER, bilirubin UDP-glucuronyl transferase (BUG-T) catalyzes the transfer of glucuronic acid (GA) from UDP-GA to bilirubin. The UDP-GA is ultimately derived from glucose. The products of the reaction are bilirubin monoglucuronide (BMG) and diglucuronide (BDG). In the adult, 80% of bilirubin is excreted into the bile as BDG; in the newborn it is predominantly as BMG.The total capacity of BUG-T to conjugate bilirubin is estimated to be 100 times the normal bilirubin load presented to the liver; therefore only a decrease in enzyme activity to 1% or less of normal would result in unconjugated hyperbilirubinemia. Many studies have demonstrated such a decrease in hepatic BUG-T activity in newborns. BUG-T activity at 17-30 weeks gestation is about 0.1% of adult levels and only increases to 1% at 30-40 weeks. Normal adult levels are not reached until 14 weeks after birth. Conjugation is therefore the rate-limiting step in bilirubin metabolism in newborns.Conditions associated with decreased UDP-GA, such as ethanol intake, infants of diabetic mothers and fasting can also lead to decreased glucuronide conjugation.Return to top of page