Bilirubin is produced in the macrophage-monocyte system by the breakdown of hemoglobin to biliverdin and then bilirubin.
When old red blood cells are destroyed by tissue macrophages, the globin portion of the hemoglobin molecule is split off,and the heme is converted to biliverdin. The enzyme involved is a subtype of hemeoxygenase and CO is formed in the process. CO is an intercellular messenger, like NO. In humans, most of the biliverdin is converted to bilirubin and excreted in the bile. The iron from the heme is reused for hemoglobin synthesis. Exposure of the skin to light converts bilirubin to lumirubin,which has a shorter half-life than bilirubin. Phototherapy (exposuretolight) is of value in treating infants with jaundice due to hemolysis. Iron is essential for hemoglobin synthesis; if blood is lost from the body and the iron deficiency is not corrected, iron deficiency anemia results.
BILIRUBIN METABOLISM &EXCRETION
Most of the bilirubin in the body is formed by the breakdown of hemoglobin. The bilirubin is bound to albumin in the circulation. Most of it is tightly bound, but some of vit can dissociate in the liver, and free bilirubin enter sliver cells via a member of the organic anion transporting polypeptide(OATP)family, and then becomes bound to cytoplasmic proteins .It is next conjugated to glucuronicacidin a reaction catalyzed by the enzyme glucuronyl transferase (UDPglucuronosyltransferase). This enzyme is located primarily in the smooth endoplasmic reticulum. Each bilirubin molecule reacts with two uridine diphosphoglucuronicacid(UDPGA) molecules to form bilirubindiglucuronide. Thisglucuronide,which is more water -soluble than the free bilirubin,is then transported against a concentration gradient most likely by an active transporter known as multidrugresistance protein-2(MRP-2)into the bile canaliculi. A small amount of the bilirubin glucuronide escapes into the blood, where it is bound less tightly to albumin than is free bilirubin, and is excreted in the urine. Thus, the total plasma bilirubin normally includes free bilirubin plus a small amount of conjugated bilirubin. Most of the bilirubin glucuronide passes via the bile ducts to the intestine.
The intestinal mucosa is relatively impermeable to conjugated bilirubin but is permeable to unconjugated bilirubin and to urobilinogens, a series of colorless derivatives of bilirubin formed by the action of bacteria in the intestine. Consequently, some of the bile pigments and urobilinogens are reabsorbed in the portal circulation. Some of the reabsorbed substances are again excreted by the liver (enterohepaticcirculation), but small amounts of urobilinogens enter the general circulation and are excreted in the urine.
Hyperbilirubinemia is a condition in which there is a build up of bilirubin in the blood, causing yellow discoloration of the eyes and skin, called jaundice.