Urobilinogen is a colorless compound found in trace amounts in urine. It represents the final stage of a metabolic process that begins with the breakdown of red blood cells. While its presence is normal, urobilinogen levels provide important information about the health and function of the liver and bile flow. The molecule transforms from a fat-soluble compound into a water-soluble substance the body can safely excrete.
The Starting Point: Heme Metabolism
The process begins in the reticuloendothelial system, where macrophages in the spleen and liver clear old red blood cells. Hemoglobin is broken down into globin, which is recycled, and heme. The heme group undergoes a two-step enzymatic reaction. Heme is first converted into the green pigment biliverdin, releasing carbon monoxide and iron. Biliverdin is then reduced to form unconjugated bilirubin, an orange-yellow pigment. Because this unconjugated form is lipid-soluble and water-insoluble, it must bind to albumin for transport through the bloodstream to the liver.
Bilirubin Processing in the Liver
When unconjugated bilirubin arrives at the liver, hepatocytes take it up from the bloodstream. Inside the hepatocyte, the enzyme UGT1A1 catalyzes conjugation. This process attaches glucuronic acid molecules to the bilirubin. The resulting product is conjugated bilirubin, which is water-soluble (“direct”) and does not require albumin for transport. The liver then secretes the conjugated bilirubin into the bile canaliculi, which leads to the small intestine.
The Creation of Urobilinogen in the Gut
Conjugated bilirubin travels with the bile into the small intestine and then reaches the large intestine. There, anaerobic bacteria use enzymes like bilirubin reductase to deconjugate and reduce it into urobilinogen. Most urobilinogen remains in the large intestine and is oxidized into stercobilin, a brown pigment that colors the feces. However, 10 to 20 percent of the urobilinogen produced is reabsorbed from the colon back into the bloodstream via the portal circulation, which leads directly to the liver.
Excretion by the Kidneys
The reabsorbed urobilinogen travels back to the liver via the portal vein. Most of it is re-extracted by hepatocytes and re-secreted into the bile as part of the enterohepatic circulation. A small amount bypasses the liver and enters the systemic circulation, where it is delivered to the kidneys. The kidneys filter this trace amount out of the blood and excrete it in the urine; the presence of 0.1 to 1.0 mg/dL is considered a normal finding. Once excreted, the colorless urobilinogen oxidizes upon exposure to air, forming urobilin, the yellow pigment that contributes to the normal color of urine.