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Unformatted text preview: Haemoglobin synthesis &
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
Haemoglobin The main function of red cells is to carry O2
to the tissues and to return carbon dioxide
(CO2) from tissues to the lungs.
(CO In order to achieve this gaseous exchange
the red cells contain the specialized protein
haemoglobin. Each red cell contains approximately 640
million Hb molecules.
million Haemoglobin synthesis
Haemoglobin 65% of the Hb is synthesized in the erythroblasts,
and 35% at the reticulocyte stage.
and 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.
ensure Globin synthesis
Globin The various globins that combine with haem to
form Hb are all single chain polypeptides.
form The synthesis of these globins is under genetic
control. Humans normally carry eight functional globin
chains, arranged in two, duplicated gene clusters:
the β-like cluster (β, γ , δ and ε globin genes) on
the short arm of chromosome 11 and the α-like
cluster (α and ζ globin genes) on the short arm of
chromosome Ontogeny of globin synthesis
Globin synthesis is first detected in the primitive
erythroid precursors of the yolk sac at about 3
weeks’ Embyonic :
Haemoglobin Gower I ( ζ2ε2)
Haemoglobin Portland ( ζ2γ 2)
Haemoglobin Gower II (α2ε2 )
Haemoglobin Fetal : HbF (α2γ 2), HbA (α2β2) Adult : HbA, HbA2 ( α2δ2), HbF.
Adult Haemoglobin Each molecule of
consists of four
α2 β2 , each with its own
Haemoglobin Normal adult blood also contains small
quantities of two other haemoglobins, Hb-F
and Hb-A2. These also contain chains but
with γ and chains respectively instead of β. The major switch from fetal to adult
haemoglobin occurs 3-6 months after birth.
haemoglobin Normal Hb in adult blood
Hb A Hb A2 Hb F structure 2β2 22 2γ 2 Normal % 96-98 % 1.5-3.2 % 0.5-0.8 % Haemoglobin synthesis
Haemoglobin Haem synthesis starts with
the condensation of
glycine and succinyl
coenzyme A under the
action of a rate limiting
acid δ-ALA will be formed. Pyridoxal phosphate (vit.
B6) iis a coenzyme for this
reaction. Haemoglobin synthesis
Haemoglobin A series of biochemical
reactions will follow.
reactions Two molecules of δ-ALA
condense to form a pyrrole
(PBG) Four PBG condense to
form a tetrapyrrole
uroporphyrinogen UPG III is then converted
to coproporphyrinogen. Haemoglobin synthesis
Haemoglobin CPG then changes to
ultimately combines with
iron in the ferrous state
(Fe2+) to form haem.
(Fe 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.
surface Transferrin releases iron
and returns back to
circulation. Haemoglobin synthesis
Haemoglobin Each molecule of
haem combines with a
globin A tetramer of four
globin chains each
with its own haem
group in a pocket is
formed to make up a
haemoglobin Haemoglobin structure
Haemoglobin Haem consists of a
protoporphyrin ring with an
iron atom at its centre.
iron The protoporphyrin ring
consists of four pyrrole
groups which are united by
methane bridges (=C-).
methane The hydrogen atoms in the
pyrrole groups are
replaced by four
methylene (CH3-), two
vinyl (-C=CH2) and two
propionic acid (-CH2-CH2propionic
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.
liver 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
1to marrow erythroblasts
2- protoporphyrin which is broken down to
3- globins which are converted to amino
3acids. 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
- Stercobilinogen and stercobilin are partly
reabsorbed and excreted in urine as
urobilinogen and urobilin.
urobilinogen Normal red cell destruction
Normal A small fraction of protoporphyrin is
converted to carbon monoxide (CO) and
excreted via the lungs.
excreted Globin chains are broken down to amino
acids which are reutilized for general protein
synthesis in the body.
synthesis Normal red cell breakdown
Expired air Amino acids Bilirubin
faeces Haemoglobin abnormalities
There are mainly two types of abnormalities,
these are :
these Quantitative abnormalities: where there is
reduction in the production of certain types
of globins e.g. α thalassaemia
thalassaemia Qualitative abnormalities: where there is
production of abnormal haemoglobin e.g.
sickle cell anaemia.
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- Fall '11