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HB Synthesis

Haemoglobin is composed of haem and globin proteins. It is synthesized in developing red blood cells through coordinated processes. Haem synthesis occurs in mitochondria and involves enzymes converting glycine and succinyl-CoA into haem, with iron at the center. Globin synthesis occurs via genetic control of polypeptide chains. Haem and globin combine to form haemoglobin tetramers. Normal adult haemoglobin is HbA, with small amounts of HbF and HbA2. Red blood cells are broken down after 120 days, releasing iron, bilirubin from haem, and amino acids from globin, which are recycled in the body. Abnormalities can be quantitative from reduced globin production or qualitative from

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126 views21 pages

HB Synthesis

Haemoglobin is composed of haem and globin proteins. It is synthesized in developing red blood cells through coordinated processes. Haem synthesis occurs in mitochondria and involves enzymes converting glycine and succinyl-CoA into haem, with iron at the center. Globin synthesis occurs via genetic control of polypeptide chains. Haem and globin combine to form haemoglobin tetramers. Normal adult haemoglobin is HbA, with small amounts of HbF and HbA2. Red blood cells are broken down after 120 days, releasing iron, bilirubin from haem, and amino acids from globin, which are recycled in the body. Abnormalities can be quantitative from reduced globin production or qualitative from

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Putri
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Haemoglobin synthesis &

catabolism
Dr. Suhair Abbas Ahmed

Haemoglobin synthesis
The haemoglobins are red globular proteins,
which have a molecular weight of about
68,000 and comprise almost one third of
the weight of a red cell.
The haemoglobin is composed of haem and
globin.

Haemoglobin synthesis
The main function of red cells is to carry O 2
to the tissues and to return carbon dioxide
(CO2) from tissues to the lungs.
In order to achieve this gaseous exchange
the red cells contain the specialized protein
haemoglobin.
Each red cell contains approximately 640
million Hb molecules.

Haemoglobin synthesis
65% of the Hb is synthesized in the erythroblasts,
and 35% at the reticulocyte stage.
Haem synthesis occurs largely in the
mitochondria.
Globin synthesis occurs in the polyribosomes.
Although haem and globin synthesis occur
separately within developing red cell precursors,
their rates of synthesis are carefully coordinated to
ensure optimal efficiency of Hb assembly.

Globin synthesis
The various globins that combine with haem to
form Hb are all single chain polypeptides.
The synthesis of these globins is under genetic
control.
Humans normally carry eight functional globin
chains, arranged in two, duplicated gene clusters:
the -like cluster (, , and globin genes) on the
short arm of chromosome 11 and the -like cluster
( and globin genes) on the short arm of
chromosome 16.

Ontogeny of globin synthesis


Globin synthesis is first detected in the primitive
erythroid precursors of the yolk sac at about 3
weeks gestation.
Embyonic :
Haemoglobin Gower I ( 22)
Haemoglobin Portland ( 22)
Haemoglobin Gower II (2)
Fetal : HbF (22), HbA (22)
Adult : HbA, HbA2 ( 22), HbF.

Haemoglobin
Normal adult blood also contains small
quantities of two other haemoglobins, Hb-F
and Hb-A2. These also contain chains but
with and chains respectively instead of .
The major switch from fetal to adult
haemoglobin occurs 3-6 months after birth.

Haemoglobin
Each molecule of
normal adult
haemoglobin (Hb-A)
consists of four
polypeptide chains
, each with its own
haem group.

Normal Hb in adult blood


Hb A

Hb A2

Hb F

structure

22

22

22

Normal %

96-98 %

1.5-3.2 %

0.5-0.8 %

Haemoglobin synthesis
Haem
synthesis
starts with
the
condensati
on of
glycine and
succinyl
coenzyme
A under the
action of a
rate limiting
enzyme aminolaevu
linic acid
synthase.
-ALA will
be formed.
Pyridoxal
phosphate
(vit. B6) is a
coenzyme
for this
reaction.

Haemoglobin synthesis
A series of biochemical
reactions will follow.
Two molecules of -ALA
condense to form a pyrrole
called porphobilinogen
(PBG)
Four PBG condense to
form a tetrapyrrole
uroporphyrinogen III.
UPG III is then converted
to coproporphyrinogen.

Haemoglobin synthesis
CPG then changes to
protoporphyrin which
ultimately combines with
iron in the ferrous state
(Fe2+) to form haem.
Iron is brought to the
developing red cells by a
carrier protein ( transferrin)
which attaches to special
binding sites on the
surface of these cells.
Transferrin releases iron
and returns back to
circulation.

Haemoglobin synthesis
Each molecule of
haem combines with a
globin chain.
A tetramer of four
globin chains each
with its own haem
group in a pocket is
formed to make up a
haemoglobin molecule.

Haemoglobin structure
Haem consists of a
protoporphyrin ring with an
iron atom at its centre.
The protoporphyrin ring
consists of four pyrrole
groups which are united by
methane bridges (=C-).
The hydrogen atoms in the
pyrrole groups are
replaced by four methylene
(CH3-), two vinyl (-C=CH2)
and two propionic acid (CH2-CH2-COOH) groups.

Haemoglobin catabolism
*normal red cell destruction*
Red cell destruction usually occurs after a mean
life span of 120 days.
The cells are removed extravascularly by
macrophages of the reticuloendothelial system
(RES), specially in the bone marrow but also in the
liver and spleen.
Red cell metabolism gradually deteriorates as
enzymes are degraded and not replaced, until the
cells become non viable, but the exact reason why
the red cells die is obscure.

Haemoglobin catabolism
*normal red cell destruction*
The breakdown of red cells liberates
1- iron for recirculation via plasma transferrin
to marrow erythroblasts
2- protoporphyrin which is broken down to
bilirubin.
3- globins which are converted to amino
acids.

Normal red cell destruction


- The bilirubin circulates to the liver where it is
conjugated to glucuronides which are
excreted into the gut via bile and converted
to stercobilinogen and stercobilin(excreted
in faeces).
- Stercobilinogen and stercobilin are partly
reabsorbed and excreted in urine as
urobilinogen and urobilin.

Normal red cell destruction


A small fraction of protoporphyrin is
converted to carbon monoxide (CO) and
excreted via the lungs.
Globin chains are broken down to amino
acids which are reutilized for general protein
synthesis in the body.

Normal red cell breakdown


haemoglobin
haem
iron

transferrin
erythroblast

Urobilin(ogen)
Urine

globin
protoporphyrin

CO
Expired air

Amino acids

Bilirubin
(free)
Liver
conjugation
Bilirubin glucuronides
Stercobilin(ogen)
faeces

Haemoglobin abnormalities
There are mainly two types of abnormalities,
these are :
Quantitative abnormalities: where there is
reduction in the production of certain types
of globins e.g. thalassaemia
thalassaemia
Qualitative abnormalities: where there is
production of abnormal haemoglobin e.g.
sickle cell anaemia.

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