Bile pigments from hemoglobin

An additional impetus for pyrrole and indole research derives from the recognition of the physiological significance of these ring systems. In the case of pyrroles the early work centered around hemin from hemoglobin and the bile pigments. The structure of chlorophyll was also shown to be pyrrole-derived. The biosynthetic connection between simple pyrroles and the macrocyclic hemin and chlorin have remained of interest up to the present (75ACR201). 

Bile salts help in the breakdown of fat in the intestines and in fat absorption through the intestinal wall. The bile salts are injected into the digestive canal at the duodenum. They are not excreted, but are almost totally absorbed through the walls of the intestine, to be used over and over again. Bile pigments are denved from the hemoglobin of broken-down red blood cells and are excreted with the feces. When the pigments appear in excessive amounts in the blood, the mucous membranes and conjunctiva of the eye become stained a pale yellow , and the patient is said to be jaundiced. 

Heme degradation Bile pigments exist in both the plant and animal kingdoms, and are formed by breakdown of the cyclic tetrapyrrole structure of heme. In animals this pathway is an excretory system by which the heme from the hemoglobin of aging red blood cells, and other hemoproteins, is removed from the body. In the plant kingdom, however, heme is broken down to form bile pigments... 

Swirl 2 g of crushed gallstones in a 25-mL Erlenmeyer flask with 15 mL of 2-butanone on a hot plate for a few minutes until the solid has disintegrated and the cholesterol has dissolved. Filter the solution while hot, taking precautions to warm the stemless funnel prior to the filtration. Its dirty-yellow appearance is from a brown residue of the bile pigment bilirubin, a metabolite of hemoglobin. 

In patients such as Will Sichel who have severe and recurrent episodes of increased red blood cell destruction (hemolytic anemia), greater than normal amounts of the red cell pigment heme must be processed by the liver and spleen. In these organs, heme (derived from hemoglobin) is degraded to bilirubin, which is excreted by the liver in the bile. 

In conclusion, bile pigment metabolism can be divided into at least seven separate steps (1) hemoglobin breakdown in the reticuloendothelial cell (2) transfer of bilirubin from the reticuloendothelial to the hepatic cell by way of the blood (3) conversion of bilirubin to bilirubin glucuronide inside the hepatic cell (4) excretion of conjugated bile in the bile duct (5) urobilinogen formation (6) urobilinogen reabsorption and (7) re-excretion of urobilinogen in feces and urine (see Fig. 6-13). 

In the body the oxidation of the heme derived from hemoglobin takes place at the a-methene link, this specific oxidation being brought about by some steric or enzymic factors as yet unknown. Watson and Schwartz have shown that human fistula bile contains bile pigment related primarily to the a-isomers, indicating that it is the a-methene carbon atom which is split out of the porph3rrin ring. 

Studies of the metabolism of bile pigment in pernicious anemia are relevant. After administration of N -labeled glycine to patients with pernicious anemia in relapse, the labeled bile pigment was too rapidly eliminated to have come from the hemoglobin of mature circulating erythrocytes (London and West, 1950). One possibility—although not the only one—is that newly formed cells are broken down within the marrow before ever reaching the circulation. 

One of the bile pigments which results from the breakdown of hemoglobin. Normally, it is excreted into the intestine with the bile. However, blockage of the biliary tract leads to accumulation of bile in the liver and blood. The buildup of pigment often imparts a yellow color to the skin (a condition called jaundice). Newborn babies are particularly prone to brain damage by elevated blood levels of bilirubin. 

Bile and blood color are due to melanin formed in the body. The two main bile pigments are bilirubin (red) and biliverdin (green). The red blood pigment is hemoglobin, from which the pigments hemosiderin, methemoglobin, bilirubin, and biliverdin are derived. 

In the plasma, bile pigment, heme and hemoglobin are not free but bound to specific proteins. Bilirubin and bilirubin di ucuronide are transported on serum dbumin and also on a specific ai-globulin (316) from R.E. cells of the body to the liver by way of the blood stream. Tlie blood in a human contains 0.2-0.8 mg total bilirubin per 100 ml plasma. 

The liver has a high capacity for removing hemoglobin molecules from the blood stream, and for converting the heme to bile pigments. Kesztjrus... 

Pigments. Bile pigments appear with hepatitis they are derived from the metabolism of hemoglobin (Chapt. IX-5). Uro- and coproporphyrins may enter the skin in cases of poisoning or of genetic defects of the biosynthesis of the hemin pigment. 

It is generally accepted that in normal subjects, most, but not necessarily all, of the bilirubin formed results from the breakdown of hemoglobin in the reticuloendothelial system. The bilirubin is then conjugated in the liver and excreted into the bile as a water-soluble pigment. The capacity of the liver to conjugate bilirubin is limited (W6), so that in cases of overproduction (e.g., hemolytic jaundice) free bilirubin will appear in the plasma. A similar result will be obtained if the ability of the liver to conjugate bilirubin is diminished (e.g., in the newborn infant). On the other hand, if the excretion of the bile is for some reason... 

---