Heme catabolism and bilirubin metabolism

1. Erythrocytes/ Red blood cells are produced in the bone marrow through erythropoiesis.
Stem cells in the bone marrow will give rise to early erythroblasts and eventually to
reticulocytes.
2. Then, reticulocytes will form erythrocytes. Both reticulocytes and erythrocytes have no
nucleus. They are anucleated cells.
3. The erythrocytes function is to circulate around our body and carry oxygen around. The
oxygen is bound to haemoglobin in the red blood cells. These erythrocytes circulate in
our body for about 120 days until they eventually get old.
4. When these cells get old or are damaged, cells known as macrophages, which are
phagocytes, located in the spleen and bone marrow will engulf these old erythrocytes
and degrade them.
5. When the erythrocytes are degraded, they will release haemoglobin molecules, which
will then be broken down into the heme and the globin.
6. Globin is an essential protein. It will be broken down into amino acids, which then
reenter the blood and are reused for erythropoiesis again.
7. Heme is broken down into unconjugated bilirubin and iron.
8. The iron will reenter the circulation and is reused for erythropoiesis again.
9. The unconjugated bilirubin however is not recycled and it needs to be removed from the
body since it is toxic. The unconjugated bilirubin that is produced has a yellowishorange colour and is actually lipid soluble. Thus, it requires a protein to carry it around
in the blood. The protein that carries the unconjugated bilirubin around is called
albumin.
10. Albumin will carry unconjugated bilirubin to the liver for further metabolism.
11. In the liver, there are own macrophages known as Kupffer cells, which will break down
old/damaged erythrocytes into heme and globin.
12. Globin will be reused into erythropoiesis and heme will be broken down into iron and
unconjugated bilirubin.
13. The iron will be reused for erythropoiesis again while the unconjugated bilirubin will be
further metabolized in the liver.
14. In the liver, the unconjugated bilirubin (lipid soluble) will be converted to conjugated
bilirubin with the addition of glucoronic acid, through conjugation process.

15. The conjugated bilirubin is now water soluble. The conjugated bilirubin can now be
excreted by the liver into bile.
16. Bile which contains conjugated bilirubin, bile salts and others will be excreted into the
small intestine through common bile duct.
17. When the conjugated bilirubin is in the small intestine, it will travel to the large intestine
or colon.
18. Towards the end of small intestine or a section called as ileum, or in the beginning of the
large intestine, the conjugated bilirubin will be converted by the intestinal bacteria to
urobilinogen, by removing the glucoronic acid through hydrolysis reduction reaction.
19. The urobilinogen is also lipid soluble. It is 10%-15% reabsorbed by the blood and bound
to albumin; and the remaining 85%-90% is quickly oxidized by other intestinal bacteria
into stercobilin, which has a brown colour pigment, and be excreted from body, giving
feces its brown colour.
20. The 10%-15% of reabsorbed stercobilin is carried by albumin back to liver through
portal system (blood).
21. About 5% of this urobilinogen will participate in interior hepatic urobilinogen cycle, in
which it is taken up by liver and resecreted into bile again.
22. The remaining/other 5% of urobilinogen is transported by blood to kidney, where it is
converted to yellow urobilin, and excreted, giving urine its yellow colour.
** The conjugated bilirubin is excreted together with bile. The bile is stored in gall
bladder, and secreted to small intestine during digestion of lipid.
** The unconjugated bilirubin is lipid soluble; and the conjugated bilirubin is water
soluble.