Formation of bile pigments

Yellow pigments are the products of the decomposition of hemoglobin and other chromoproteins - myoglobin, cytochromes and heme-containing enzymes. The bile pigments include bilirubin and urobilin bodies - urobilinoids.

Under physiological conditions in an adult human body, 1-2 × 10 ⁸ erythrocytes are destroyed in one hour . The released hemoglobin is destroyed by the protein part (globin) and the part containing iron (heme). The heme iron is included in the total iron exchange and is again used. The iron-free porphyrin part of the heme undergoes catabolism, which mainly occurs in the reticuloendothelial cells of the liver, spleen, and bone marrow. Metabolism of heme is carried out by a complex enzyme system - hemoxygenase. By the time heme comes from the heme proteins into the hemoxygenase system, it is converted to hemin (oxidized iron). Hemin, as a result of a series of successive oxidation-reduction reactions, is metabolized to biliverdin, which, being reduced by the action of biliverdin reductase, turns into bilirubin.

Further metabolism of bilirubin mainly occurs in the liver. Bilirubin is poorly soluble in plasma and water, therefore, to enter the liver, it specifically binds to albumin. In connection with albumin, bilirubin is delivered to the liver. In the liver, there is a transition of bilirubin from albumin to the sinusoidal surface of hepatocytes with the participation of a saturated transfer system. This system has a very large capacity and, even in pathological conditions, does not limit the metabolic rate of bilirubin. In the future, the metabolism of bilirubin consists of three processes:

• absorption by parenchymal cells of the liver;
• conjugation of bilirubin in the smooth endoplasmic reticulum of hepatocytes;
• secretion from the endoplasmic reticulum to bile.

In hepatocytes, polar groups are attached to bilirubin, and it passes into a water-soluble form. The process that ensures the transition of bilirubin from water insoluble to water-soluble form is called conjugation. First, the formation of monoglyukuronide bilirubin (in the endoplasmic reticulum of hepatocytes), and then diglucuronide bilirubin (in the tubules of the hepatocyte membrane) with the enzyme uridine diphosphate glucuronyl transferase.

Bilirubin is secreted into the bile mainly in the form of diglukuro-nid bilirubin. Secretion of conjugated bilirubin in bile occurs against a very high concentration gradient with the participation of active transport mechanisms.

In the bile, conjugated (over 97%) and unconjugated bilirubin enters the small intestine. After bilirubin reaches the ileum and large intestine, the glucuronides are hydrolyzed by specific bacterial enzymes (β-glucuronidases); further intestinal microflora restores pigment with consecutive formation of mesobilirubin and mesobilinogen (urobilinogen). In the ileum and large intestines, a part of the mesobilinogen (urobilinogen) formed is absorbed through the intestinal wall, enters the portal vein and enters the liver, where it is completely digested to dipyrrole, so the normal mesobilinogen (urobilinogen) does not enter the general circulation and urine. If the liver parenchyma is damaged, the process of cleavage of mesobilinogen (urobilinogen) to dipyrrole is broken and urobilinogen passes into the blood and thence into urine. Normally, most of the colorless mesobylinogens formed in the large intestine are oxidized into sterocobilinogen, which in the lower parts of the colon (mainly in the rectum) is oxidized to sterocilin and excreted with feces. Only a small part of the sterkobilinogen (urobilin) is absorbed in the lower parts of the colon into the system of the inferior vena cava and is subsequently excreted by the kidneys with urine. Therefore, in normal 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 sulphate and 10% in complex with other substances.

[1], [2], [3], [4], [5], [6], [7]