Hemoglobin (Hb) is the protein in red blood cells (RBCs) responsible for carrying oxygen from the lungs to the body’s tissues. The average lifespan of an RBC is approximately 120 days. When these cells become old or damaged, the body initiates a precise process to dismantle and recycle hemoglobin components. This systematic breakdown conserves valuable materials and prepares waste products for safe elimination.
Initial Isolation: Separating Hemoglobin Components
Aged red blood cells are consumed by specialized immune cells called macrophages, primarily situated within the reticuloendothelial system (spleen, liver, and bone marrow). Inside the macrophage, hemoglobin is separated into its two primary constituents: the protein component globin and the iron-containing prosthetic group heme.
The globin portion, composed of four polypeptide chains, is rapidly broken down into amino acids. These free amino acids are released back into the body’s pool for reuse in the synthesis of new proteins. This process isolates the heme group, which is destined for the complex chemical breakdown pathway.
The First Transformation: From Heme to Unconjugated Bilirubin
The heme group remains within the macrophage for a two-step enzymatic conversion. Heme Oxygenase (HO) acts on the cyclic heme structure to open the ring. This oxidation releases the iron atom and produces the green pigment Biliverdin.
The released iron atom binds to transport proteins like transferrin and is carried to the bone marrow for new red blood cell production. Biliverdin is then acted upon by Biliverdin Reductase, converting the pigment into the yellow pigment known as Unconjugated Bilirubin.
Unconjugated bilirubin is highly hydrophobic and lipid-soluble, meaning it does not dissolve easily in water. Since it cannot be freely transported in the bloodstream or easily excreted, it requires further processing for safe transport and elimination.
Liver Processing: Conjugation and Transport
Because unconjugated bilirubin is hydrophobic, it cannot travel independently. It is promptly bound to the plasma protein Albumin, which safely escorts it through the circulation toward the liver.
In the liver, hepatocytes take up the unconjugated bilirubin for conjugation. The enzyme Uridine Glucuronyl Transferase (UGT) catalyzes a reaction that attaches one or two molecules of glucuronic acid. This process results in the formation of Conjugated Bilirubin (Bilirubin Mono- or Diglucuronide).
The addition of glucuronic acid makes the conjugated form water-soluble (hydrophilic), which is required for safe excretion. Conjugated bilirubin is actively secreted by the hepatocytes into the bile canaliculi. This molecule is a primary component of bile, which is released into the small intestine.
Final Excretion Pathways and End Products
Conjugated bilirubin travels with the bile into the small intestine. In the lower gastrointestinal tract, gut bacteria remove the glucuronic acid molecules and reduce the bilirubin. This conversion creates a colorless intermediate compound called Urobilinogen.
Urobilinogen follows one of two final excretion routes. The majority remains in the intestine, where bacterial flora convert it into Stercobilin. This brown pigment is excreted in the stool, giving feces its characteristic coloration.
A smaller fraction (10 to 20 percent) is reabsorbed into the bloodstream. Most returns to the liver for re-excretion in the bile, a cycle known as the enterohepatic circulation. A small amount bypasses the liver, travels to the kidneys, and is converted into the yellow pigment Urobilin, which is excreted in the urine.