Lecture Note
Hemoglobin. Syntethis, structure and function
-
University:
American Career College -
Course:
NURS112 | Fundamentals of Nursing Academic year:
2019
-
Views:
483
Pages:
29
Author:
BetaRiku
Introduction
•
•
The hemoglobin are red globular
proteins which have a molecular
weight of about 64,500 and comprise
almost one third of the weight of a red
cell. Their primary function is the
carriage of oxygen from the lungs to
the tissues.
Over 500 different haemoglobin
variants have been described but all
share the same basic structure of four
globin polypeptide chains each with
haem group. Functional haemoglobin
composed of two pairs of dissimilar
globins. Why we need HG?
Solubility of O2 in blood is •
too low (0.0001M) under
physiological conditions)
to carry sufficient
amounts of O2 for
metabolic needs
Whole blood, contains150 •
g of Hb /L, can carry O2 at
concentrations as high as
0.01M,about the same as
in air RED Blood Cells and Hemoglobin
Red Blood Cells (RBC) or Erythrocyte
Male: 4.5-5.5 million
Female: 4.2-4.8 million
Hemoglobin:
Male: 12-16 g/dL
Female: 11.5-15.0 g/dL
It is estimated 5% of the word’s total population, carries
a hemoglobin mutation and that over 350 000 children
are born each year with a serious disorder of
hemoglobin structure Chromosomal Arrangement for
Hemoglobin Genes Adult haemoblobin
Hb A
Hb A2
Hb F
structure
a2b2
a2d2
a2g2
Normal %
96-98 %
1.5-3.2 %
0.5-0.8 % Quaternary structure of Haemoglobin
The quaternary structure of haemoglobin
has four
subunits arranged tetrahedrally. In adult
haemoglobin- (HbA), there are different
contact
areas:
•
•
•
α1β1 and α2 β 2 which confirms
stability of the molecule.
α1 β2 and α2 β1 which
confirms solubility of the
molecule.
α1 α2 and β1 β2 which are
weak bonds to permit
oxygenation and deoxygenation. Hemoproteins
Hemoglobin •
Myoglobin •
Cytochromes •
Catalase •
Peroxidases •
C
D
B
A Heme Binding
Oxygen
N
N
Fe
N
N
Histidine Hemoglobin and Myoglobin Oxygen
Saturation and Allosteric Regulation
T
R Normal Hemoglobin Function
•
•
•
•
When fully saturated, each gram of
hemoglobin binds 1.34 ml of oxygen.
The degree of saturation is related to
the oxygen tension (pO2), which
normally ranges from 100 mm Hg in
arterial blood to about 35 mm Hg in
veins.
The relation between oxygen tension
and hemoglobin oxygen saturation is
described by the oxygen-dissociation
curve of hemoglobin.
The characteristics of this curve are
related in part to properties of
hemoglobin itself and in part to the
environment within the erythrocyte,
including pH, temperature, ionic
strength, and concentration of
phosphorylated compounds,
especially 2,3-diphosphoglycerate
(2,3-DPG). Normal Hemoglobin Function
• Oxygen affinity of hemoglobin is generally expressed in
terms of the oxygen tension at which 50% saturation
occurs.
• When measured in whole erythrocytes, this value
averages 27.1 mm Hg in normal, nonsmoking males and
27.5 mm Hg in normal, nonsmoking females.
• When oxygen affinity is increased, the dissociation
curve is shifted Leftward, and the value is reduced.
• Conversely, with decreased oxygen affinity, the curve is
shifted to the right. Bohr Effect On Hemoglobin
Saturation
Hb -4O2 + nH+ → HbH+ + 4 O2
Increase in CO2,
Decrease in pH
Both Shift O2
Saturation Curve
to the right
Amino terminal α-amino group +
CO2 R-NH-COO- (Carbamate) Structural Basis of The Bohr Effect
1- His 146 on the ß chain is
positively charged, and can
participate in an ionic
interaction with Asp 94,
which stabilizes the T state
2- Carbon dioxide can react with the
positively charged amino termini to
form negatively charged Carbamate
groups that form ionic interactions
which also stabilize the T state Inspiration and Expiration in Lung Effects of 2,3bisphosphoglycerate
A single molecule of 2,3-BPG binds to a
positively charged cavity formed by the
β-chains of deoxyhemoglobin
2,3- BPG
High Altitude
COPD
Chronic hypoxia
Chronic anemia Fetal Hemoglobin Oxygen Saturation
Serine 143
↓ Hb-oxygen dissociation curve
Right shift (easy oxygen delivery)
High 2,3-DPG
High H+
High CO2
HbS
Left shift (give up oxygen less readily)
Low 2,3-DPG
HbF Derivatives of Hemoglobin
Oxyhemoglobin
Deoxyhemoglobin
Methemoglobin
Carbonylhemoglobin (HbCO)
Carbaminohemoglobin (HbCO2)
Glycohemoglobin (HbA1c)
Glucose residues attached predominantly to the NH2
groups of the N-terminal valines of the β-globin chains Mutations in hemoglobin (hemoglobinopathies:
1- Sickle cell anemia (Hb S disease):
It is a genetic disorder of blood caused by mutation in β-globin chain resulting in the
formation of Hb S. The mutation occurs in 6th position of β-chain where glutamic acid
is replaced by valine (non polar). Valine residues aggregate together by hydrophobic
interactions leading to precipitation of Hb within RBCs. RBCs assume sickle-shaped
leading to fragility of their walls and high rate of hemolysis. Sickle Cell Hemoglobin
Normal RBC
Sickle RBC Selective Advantage of HBS Heterozygote Classification of Thalassemia
chromosome 16
ß-Thalassemia
Homozygote for severe ߺThalassemia require life-long
treatment with blood
transfusion and iron
chelation therapy -α-thalassemia: in which synthesis of α globin chain
is defective or
absent. There are four
copies of gene responsible for synthesis of α globin
chains so patients may have:
i - Silent carrier of α-thalassemia with no
symptoms:
if one gene is defective
ii- α-thalassemia trait: if two genes are defective.
iii- Hb H disease: if 3 α globin genes are defective,
with mild to moderate anemia. The produced Hb will
be β4 which is called HB H. Oxygen delivery to
tissues will be blocked because Hb H (β4 ) has high
affinity to O2 and not deliver it to tissues.
iv- Hydrops fetalis: when all 4 α globin genes are
defective. It causes fetal death because α globin
chains are required for synthesis of Hb F.
Hemoglobin. Syntethis, structure and function
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