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The formation of bile pigments
Last reviewed: 04.07.2025
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Bile pigments are the breakdown products of hemoglobin and other chromoproteins - myoglobin, cytochromes and heme-containing enzymes. Bile pigments include bilirubin and urobilin bodies - urobilinoids.
Under physiological conditions, 1-2×10 8 erythrocytes are destroyed in an adult human body per hour. The hemoglobin released in this process is broken down into a protein part (globin) and a part containing iron (heme). The iron of heme is included in the general iron metabolism and is used again. The iron-free porphyrin part of heme is subject to catabolism, which mainly occurs in the reticuloendothelial cells of the liver, spleen and bone marrow. Heme metabolism is carried out by a complex enzyme system - heme oxygenase. By the time heme enters the heme oxygenase system from heme proteins, it is converted into hemin (iron is oxidized). Hemin, as a result of a number of successive oxidation-reduction reactions, is metabolized into biliverdin, which, being reduced by biliverdin reductase, is converted into bilirubin.
Further metabolism of bilirubin occurs mainly in the liver. Bilirubin is poorly soluble in plasma and water, therefore, in order to enter the liver, it specifically binds to albumin. Bilirubin is delivered to the liver in connection with albumin. In the liver, bilirubin is transferred from albumin to the sinusoidal surface of hepatocytes with the participation of a saturable transfer system. This system has a very large capacity and even in pathological conditions does not limit the rate of bilirubin metabolism. Subsequently, bilirubin metabolism consists of three processes:
- absorption by liver parenchymal cells;
- conjugation of bilirubin in the smooth endoplasmic reticulum of hepatocytes;
- secretion from the endoplasmic reticulum into bile.
In hepatocytes, polar groups are attached to bilirubin, and it becomes water-soluble. The process that ensures the transition of bilirubin from a water-insoluble to a water-soluble form is called conjugation. First, bilirubin monoglucuronide is formed (in the endoplasmic reticulum of hepatocytes), and then bilirubin diglucuronide (in the canaliculi of the hepatocyte membrane) with the participation of the enzyme uridine diphosphate glucuronyl transferase.
Bilirubin is secreted into bile primarily as bilirubin diglucuronide. Secretion of conjugated bilirubin into bile occurs against a very high concentration gradient with the participation of active transport mechanisms.
Conjugated (over 97%) and unconjugated bilirubin enters the small intestine as part of the bile. After bilirubin reaches the ileum and colon, glucuronides are hydrolyzed by specific bacterial enzymes (β-glucuronidases); then the intestinal microflora restores the pigment with the sequential formation of mesobilirubin and mesobilinogen (urobilinogen). In the ileum and colon, part of the resulting mesobilinogen (urobilinogen) is absorbed through the intestinal wall, enters the portal vein and enters the liver, where it is completely broken down to dipyrroles, so normally mesobilinogen (urobilinogen) does not enter the general circulation and urine. When the liver parenchyma is damaged, the process of breaking down mesobilinogen (urobilinogen) into dipyrroles is disrupted and urobilinogen passes into the blood and from there into the urine. Normally, most of the colorless mesobilinogens formed in the large intestine are oxidized into stercobilinogen, which in the lower parts of the large intestine (mainly in the rectum) is oxidized to stercobilin and excreted with feces. Only a small part of stercobilinogen (urobilin) is absorbed in the lower parts of the large intestine into the inferior vena cava system and is subsequently excreted by the kidneys with urine. Consequently, normally human urine contains traces of urobilin, but not urobilinogen.
The combination of bilirubin with glucuronic acid is not the only way to neutralize it. In adults, 15% of bilirubin contained in bile is in the form of sulfate and 10% in a complex with other substances.
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