Download Haemoglobin (Roll no. 22

•Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red
blood cells of vertebrates.
•Hemoglobin transports oxygen from the lungs or gills to the rest of the body, such
as to the muscles, where it releases the oxygen for cell use.
•It also has a variety of other roles of gas transport and effect-modulation which
vary from species to species, and are quite diverse in some invertebrates.
• Haemoglobin contains a haem group that has an iron atom at its centre. When
the iron is bound to oxygen, the haem group is red in colour (oxyhameoglobin),
and when it lacks oxygen (deoxygenated form) it is blue-red.
Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is
synthesized in a series of steps in the mitochondria and the cytosol of immature
red blood cells, while the globin protein parts are synthesized by ribosomes in the
cytosol. Production of Hb continues in the cell throughout its early development
from the proerythroblast to the reticulocyte.
• Haemoglobin
molecule is an assembly of four globular protein
subunits. Each subunit is composed of a protein chain tightly
associated with a non-protein heme group. Each protein chain
arranges into a set of alpha-helix , structural segments connected
together in a globin fold arrangement. This folding pattern contains
a pocket which strongly binds the heme group.
• A heme group consists of an iron (Fe) ion (charged atom) held in a
heterocyclic ring, known as a porphyrin. The iron ion, which is the
site of oxygen binding, coordinates with the four nitrogens in the
center of the ring, which all lie in one plane. The iron is also bound
strongly to the globular protein via the imidazole ring of the
histidine residue below the porphyrin ring. A sixth position can
reversibly bind oxygen, completing the octahedral group of six
ligands.
• In adult humans, the most common hemoglobin type is a tetramer (which
contains 4 subunit proteins) called hemoglobin A, consisting of two α and two β
subunits non-covalently bound, each made of 141 and 146 amino acid residues,
respectively. This is denoted as α2β2. Hemoglobin A is the most intensively studied
of the hemoglobin molecule.
• The four polypeptide chains are bound to each other by salt bridges, hydrogen
bonds, and hydrophobic interactions. There are two kinds of contacts between the
α and β chains: α1β1 and α2β2.
• Hemoglobin F is an immature form of Hb is composed of 2 α and 2 γ
chains.
• Its life span is about 2 weeks.
• It has more affinity towards o2 than HbA. This is due to the fact that it
does not interact
with 2,3,-DPG (it lowers the o2 binding capacity of
haemoglobin).
• It is less resistant to alkali denaturation.
: Hemoglobin A2 is a normal variant of hemoglobin A that consists
of two alpha and two delta chains and is found in small quantity in
normal human blood.
it is a form of hemoglobin, in which the iron in the heme group
is in the Fe3+ state, not the Fe2+ of normal hemoglobin. Methemoglobin
cannot carry oxygen.
a 2 bs 2
A variant form of hemoglobin found in people with sickle
cell anemia. There is a variation in the β-chain gene, causing a change
in the properties of hemoblobin which results in sickling of red blood cells.
• The oxygen molecule binds to Hb as a neutral ligand(ligand binding) and hence
the process is known as oxygenation and not oxidation as the oxidation state of Fe
remains +2.
• When oxygen binds to the iron center, it causes contraction of the iron atom, and
causes it to move back into the center of the porphyrin ring plane . At the same
time, the porphyrin ring plane itself is pushed away from the oxygen and toward
the imidizole side chain of the histidine residue interacting at the other pole of
the iron. This causes a tug on the peptide strand which tends to open up heme
units in the remainder of the molecule, so that there is more room for oxygen
molecules to bind at their heme sites.
• Hence, when one subunit protein in hemoglobin becomes oxygenated, this
induces a conformational or structural change in the whole complex, causing the
other subunits to gain an increased affinity for oxygen. As a consequence, the
oxygen binding curve of hemoglobin is sigmoidal, or S-shaped, as opposed to the
normal hyperbolic curve associated with noncooperative binding.
Binding and release of ligands induces a conformational (structural) change in
hemoglobin. Here, the binding and release of oxygen illustrates the structural
differences between oxy- and deoxyhemoglobin, respectively. Only one of the four
heme groups is shown.
• Decrease of hemoglobin, with or without an absolute decrease of red blood cells,
leads to symptoms of anemia. As absence of iron decreases heme synthesis, red
blood cells in iron deficiency anemia are hypochromic (lacking the red
hemoglobin pigment) and microcytic (smaller than normal).
• Sickle Cell Anemia: Sickle cell anemia, also known as sickle cell disease, is
caused by a point mutation in the b globin gene. As a result of this mutation,
valine is inserted into the 6th position in the b globin chain instead of glutamic
acid . The hemoglobin sticks together when it delivers oxygen to the body’s
tissues. These clumps of hemoglobin are like liquid fibers. They cause the red
blood cells to become stiff and shaped like a sickle.
• Thalassemia: it is an inherited autosomal recessive blood disease. In
thalassemia, the genetic defect results in reduced rate of synthesis of one of the
globin chains that make up hemoglobin. Reduced synthesis of one of the globin
chains can cause the formation of abnormal hemoglobin molecules, and this in
turn causes the anemia which is the characteristic presenting symptom of the
thalassemias.