Presentation Notes on
Hemoglobin Life Cycle / Span/ Fate and Breakdown Products & Pathway for
Medical Biology Students in word/ .ppt/ .pdf Format
FATE OF HEMOGLOBIN
As
stated previously, when the erythrocytes (RBC) become old, they rupture, mostly
in spleen (as well as in the liver and bone marrow). The Hb, is liberated from
the ruptured RBC and phagocytozed by the phagocytes of reticulo
endothelialsystem.Within the phagocytes, the tetrapyrrole ring is opened up,
that is, the haem is converted into a compound where the four pyrrole rings lie
side by side.The iron is still attached with the tetrapyrrole straight chain
compound and probably the globin also remains attached with it. Subsequently
both globin and iron are removed. The tetrapyrrole straight chain compound thus
formed (free from iron and globin) is called biliverdin.
Biliverdin
is oxidized to form bilirubin. All
these changes occur within the phagocyte of the reticuloendothelial
system.'Bilirubin now comes out of the phagocyte and, in the plasma, combines
with albumin and is transported in, the plasma as bilirubin-albumin complex.
This complex is frequently called "free bilirubin" by the clinicians
and clinical biochemists.
The free bilirubin ultimately
enters the liver and here the albumin is removed from the free bilirubin and
most of the 'bilirubin is conjugated with glucuronic acid (a derivative of
glucose), to form bilirubin glucuronides, which is water soluble. A small
amount of bilirubin is conjugated with sulphate radicals to form bilirubin
sulphate. The conjugated water soluble bilirubin is called "conjugated
bilirubin".
The
conjugated bilirubin is discharged into the biliary canaliculi and gets mixed up with bile. This is the main
coloring matter of the bile.Via the bile, the conjugated bilirubin ultimately
enters the duodenum. In the intestine, when it comes in contact with the
intestinal bacteria, bilirubin glucuronide is hydrolyzed by bacterial enzymes
and non-conjugated bilirubin, which also is, unfortunately, called free
bilirubin, is formed (unfortunate, because the term 'free', can create a
confusion; whether it means bilirubin albumin complex or it is bilirubin
obtained by unconjugation of the glucuronides). This free bilirubin is reduced
to form urobilinogens and sterco bilinogens. Part of the urobilinogens and
stercobilinogens are absorbed by blood which then circulate in the blood and
is excreted via the urine. The rest (ie. that part which was not absorbed from
the gut) is excreted via stool. Golden yellow color of the stool is due to
these pigments (stercobilinogen), and if the stool be kept exposed to the sun
and air, the color becomes blackish because of oxidation of these pigments.
The
conjugation (with glucuronic acid) of bilirubin in liver is catalyzed by the
enzyme glucurony ltransferase.Many drugs, especially some steroids compete with
bilirubin for conjugating with glucuronic acid. Unless bilirubin conjugates
with glucuronic acid it cannot be excreted via bile. So excessive use of these
drugs often lead to accummulation of "free bilirubin" in the plasma
(jaundice).
All
conditions which produce excessive erythrocyte destruction, eg., malaria,
mismatched blood transfusion, erythroblastosis fetalis, bites by some types of
poisonous snakes, thus lead to excessive "free bilirubin' (ie, bilirubin-albumin
complex) formation, and jaundice, clinically called,hemolytic jaundice,
develops. But the urine' does not contain free bilintbin in hemolytic jaundice,
as the compound (ie, bilintbin-albumin complex) cannot pass the renal filter
(owing to its big size). Instead, the urine contains excessive urobilinogen.
The normal bilirubin concentration of plasma is between 0:5 to 1.0 mg/100 ml,
which rises greatly in hemolytic jaundice.
Download Notes / Presentation on Hemoglobin Breakdown
Download Notes / Presentation on Hemoglobin Breakdown
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