Bilirubin formation begins with the breakdown of aged or damaged red blood cells in the spleen. Hemoglobin is split into heme and globin. Heme is further degraded by heme oxygenase to biliverdin, which is then reduced to bilirubin. This unconjugated bilirubin is transported to the liver bound to albumin, where it is conjugated with glucuronic acid by the enzyme UDP-glucuronosyltransferase, making it water-soluble.