The following points highlight the two main heads of catabolism. The heads are: 1. Conversion of Hemoglobin to Bile Pigments 2. Metabolism of Bile Pigments.
Catabolism: Head # 1.
Conversion of Hemoglobin to Bile Pigments:
a. About 8 grams of hemoglobin is broken down each day in the normal adult and this amount contains 27 mg of iron. The protoporphyrin yields about 300 mg of bilirubin.
b. When hemoglobin is catabolized in the body, the protein portion globin is reutilized either as such or in the form of its constituent amino acids, and the iron enters ferritin “Pool” for reuse.
c. The porphyrin portion is broken down mainly in the reticuloendothelial cells of the liver, spleen and bone marrow.
d. First, it involves the opening of the porphyrin ring between pyrrole residue 1 and II and elimination of the alpha methylene carbon as carbon monoxide (CO). The iron is still present.
e. Such a green conjugated protein formed by the oxidation of hemoglobin by oxygen in presence of ascorbic acid is said to be choleglobin.
f. Then biliverdin is converted to bilirubin by bilirubin reductase in the presence of NAD+ or NAD+.
Normally, there are only slight traces of biliverdin in human bile but the colour is very intense. Watson (1969) states that biliverdin jaundice is largely limited to (i) biliary obstruction as a result of carcinoma, (ii) Severe parenchymal liver disease as in advanced cirrhosis of the liver.
The amounts of biliverdin in the serum are very small in obstructive jaundice caused by the presence of a stone in the common bile duct. No biliverdin occurs in the serum in hemolytic jaundice.
Catabolism: Head # 2.
Metabolism of Bile Pigments:
a. The normal concentration of bilirubin in human plasma is 0.3-1.1 mg/dl. One gram of hemoglobin yields 35 mg of bilirubin which is carried in loose association with albumin of the plasma by systemic circulation.
b. Then it is carried to the liver. UDP-glucose is converted to UDP-glucuronic acid by UDP-glucose dehydrogenase.
c. In liver cell, UDP glucuronic acid conjugates with bilirubin by the enzyme UDP- glucuronyl transferase. As a result, there is formation of bilirubin monoglucuronide and UDP.
d. Bilirubin monoglucuronide reacts with UDP-glucuronic acid to form bilirubin diglucuronide and UDP by the help of the above-mentioned enzyme.
e. Mono and di-glucuronides of bilirubin are called conjugated bilirubin’s. Conjugated bilirubin can pass through glomerular filter and appear in urine (bilirubinuria). But unconjugated bilirubin cannot pass through glomerular filter. Glucuronyl transferase activity is inhibited by certain drugs e.g.,—novobiocin, pregnancy etc.
f. In the lower portions of the intestinal tract, the cecum and the colon, the bilirubin is released from the conjugate and is then reduced by enzyme systems present in the intestinal tract, mainly derived from anaerobic bacteria in the cecum.
g. Progressive hydrogenation takes place to produce a series of intermediary compounds, beginning with mesobilirubinogen which is oxidized with the loss of hydrogen to coloured compounds. The end product is colourless L-stercobilinogen (L-urobilinogen).
Auto-oxidation in the presence of air produces stercobilin (L-urobilin), an orange-yellow pigment which gives the normal colour of the feces. Stercobilin is strongly levorotatory.
h. A portion of the urobilinogen is reabsorbed from the intestine into the blood and enters into gall bladder by enterohepatic circulation.
i. Some of this is excreted by the kidney and appears in the urine in the concentration of 0-2.4 mg/day. The unabsorbed urobilinogen is excreted in the stool (40-280 mg/day). On exposure to oxygen, urobilinogen is oxidized to urobilin which gives the darkening of stools.