Bile pigments and bile salts

Catabolism of heme:

When hemoglobin is destroyed in the body, the protein portion, globin, may be reutilized either as such or in the form of its constituent amino acids, and the iron of heme enters the iron pool, also for re-use. However, the iron free porphyrin portion of heme is degraded, mainly in the reticuloendothelial cells of the liver, spleen and bone marrow.

The catabolism of heme from all the heme proteins appears to be carried out in the microsomal fraction of the reticuloendothelial cells by a complex enzyme system called heme oxygenase. By the time the heme of heme proteins reaches the heme oxygenase system, the iron has usually been oxidized to the ferric form, constituting hemin and may be loosely bound to albumin as methemalbumin. The hemin is reduced to heme with NADPH, and with aid of more NADPH, oxygen is added to the a-methenyl bridge between pyrroles I and II of the porphyrin. The ferrous iron is again oxidized to the ferric form. With the further addition of oxygen, ferric ion is released, carbon monoxide is produced and an equimolar quantity of biliverdin IX-a results from the splitting of the tetrapyrrole ring. The heme itself participates in this reaction as a catalyst. In birds and amphibian, the green biliverdin IX-a is excreted; in mammals, a soluble enzyme called biliverdin reductase reduces the methenyl bridge between pyrrole III and pyrrole IV to a methylene group to produce bilirubin IX-a, a yellow pigment (The major pigment in human bile).

Combination of bilirubin with plasma proteins, albumin forms hemobilirubin (plasma bilirubin, unconjugated or indirect bilirubin).Hemobilirubin is then carried to the liver where it leaves the albumin fraction and bilirubin is conjugated to glucuronic acid to form cholebilirubin (direct or conjugated bilirubin) which is excreted with bile into the intestine.

Bilirubin is reduced under the effect of intestinal flora to form sterchobilinogen which is converted into sterchobilin by auto oxidation. Part of the sterchbilinogen is re-absorbed from the intestine to be excreted by the kidney into urine (urobiliogen). Urobilinogen by auto oxidation in urine is converted to urobilin. Another part of sterchobilinogen is excreted in bile after reabsorption.

N.B. Cholebilirubin (direct or conjugated): is of a small molecular weight and so when increased in blood it can pass through the renal glomeruli to be excreted in urine. The urine in such conditions will be deep brown in color. Plasma bilirubin (hemobilirubin or unconjugated): is of a large molecular weight and if increased in blood it will not appear in urine.