Download Lecture 3 HAEMOGLOBIN

HAEMOGLOBIN
Normal iron metabolism:
 The primary function of the RBC is oxygen and CO2 transport.
 In order to achieve this function, they contain the specialized
protein, HAEMOGLOBIN. Each red cell contains approximately
640 million haemoglobin molecules.
 Each haemoglobin molecule is composed of Iron (Haem) and
globin (protein portion).
 Each globin part consists of four polypeptide chains ά 2 ß 2.
 The normal adult contains three types of haemoglobin: Hb A, Hb
F and Hb A2.
 Iron is absorbed by duodenum and jejunim
 Average total body iron content 3500-4000 mg.
 Approximately 2/3 found in hemoglobin,
 Iron is also stored in RE cells (BM, Spleen and liver) as
hemosiderin and ferratin.
 Also iron found in myglobin and myeloperoxidase and in certain
electron transfer.
 Iron is more stable in ferric state (Fe+++) than in ferrous state
(Fe++).
 The main function of the RBCs is to carry O2 to the tissues and to
return carbon dioxide to the lungs.
Normal Haemoglobins in adult blood.
Structure
Normal (%)
Hb A
α2ß2
96-98
Hb F
α2 γ2
0.5-0.8
5
Hb A2
α2 δ2
1.5-3.2
The major switch from fetal to adult haemoglobin occurs 3-6 months
after birth. 65% of Hb is synthesized in the erythroblast and 35 % at the
reticulocyte stage. Haem synthesis occurs largely in the mitochondria by
a series of biochemical reactions commencing with the condensation of
glycine and succinyle co-enzyme A under the action of the key ratelimiting enzyme Gamma aminolevulinic acid synthetase (ð ALA
synthetase). Vitamin B6 is an essential cofactor in the reaction.
Haemoglobin structure:
 The hemoglobin molecule is a tetramer composed of four globin
chains, each of which contains a haem ring.
 Haem consists of a protoporphyrin ring into which a ferrous iron
atom has been inserted.
 The initial reaction in the haem synthesis pathway is the
combination of glycine and succinyl coenzyme A (CoA) to form
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alpha -aminolevulinic acid (ALA), which is catalyzed by the
enzyme aminolevulinic acid synthetase (ALA synthetase).
 Vitamin B6 is an essential cofactor in the reaction.
 The final step in the pathway is insertion of the ferrous iron atom
into protoporphyrin.
 Defects in various enzymes in the haem synthesis pathway cause
many diseases.
Normal adult red cell values:
Male
Female.
Haemoglobin (g/dl)
13.5-17.5
11.5-15.5
Haematocrite (PVC) %
40-52
36-48
Red cell count (x10 12/l)
4.5-6.5
3.9-5.6
Mean cell haemoglobin (MCH pg)
27-34
Mean cell volume (MCV fl)
80- 95
Mean cell haemoglobin concentration 30-35
(MCHC g/dl)
Reticulocyte count %
0.5-2
Absolute Values (Red cell indices):
PCV% x 10
--------------
1- mean cell volume =
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RBC count.
2- mean cell haemoglobin =
Hb (g/dl) x 10
-----------------RBC count.
3- mean cell haemoglobin concentration =
Hb (g/dl) x 100
------------------RBC count.
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