HEMOGLOBIN

Hemoglobin is a tetramers composed of pairs of two polypeptide sub units. It transports O2 to

tissues and returns CO2 and protons to the lungs. The primary, secondary, and tertiary structures are
same as myoglobin. It is compose of heme and globin. Heme prosthetic group of hemoglobin, it has a
porphyrin part (organic part) and mediates reversible binding of oxygen by hemoglobin. Globin is the
protein part which surrounds and protects the heme.

It has more than 1 subunit – quaternary structure: 2 alpha and 2 beta subunits, cooperativity
exhibited in binding and release of O2. Alpha subunits 141 residues and Beta subunits has 146 residues.
Subunit composition of the principal hemoglobins: a2B2 (HbA; normal adult hemoglobin), a2y2 (HbF:
fetal hemoglobin), a2S2 (HbS; sickle cell hemoglobin) and a2δ2 (HbA2; minor adult hemoglobin).

Hemoglobin Synthesis
Hemoglobin synthesis requires the
coordinated production of heme and globin.
Synthesis of hemoglobin begins in the
proerythroblasts and continues even into the
reticulocyte stage of red blood cells. The
process begins in the mitochondrion with the
condensation of succinyl-CoA, then binds with
glycine to form a pyrrole molecule. In turn, four
pyrroles combine to form protoporphyrin IX,
which then combines with iron to form the
heme molecule. Finally, each heme molecule
combines with a long polypeptide chain, a
globin synthesized by ribosomes.
Two distinct globin chains, each with its
individual heme molecule, combine to form
hemoglobin. One of the chains is designated
alpha. The second chain is called non-alpha.
With the exception of the very first weeks of
embryogenesis, one of the globin chains is
always alpha. A number of variables influence
the nature of the non-alpha chain in the
hemoglobin molecule. The fetus has a distinct
non-alpha chain called gamma. After birth, a
different non-alpha globin chain, called beta, a
pairs with the alpha chain. The combination of
two alpha chains and two non-alpha chains
produces a complete hemoglobin molecule.
In relation, to the hemoglobin synthesis, it is important to know that iron is delivered by
a specific transport protein, transferrin, to the membrane of the immature cell. Iron in the ferric
form is affixed to the cell membrane, and the transferrin is released back to the plasma. Most
of the iron entering the cell is committed to hemoglobin synthesis and proceeds to the
mitochondrion, where it is inserted into the protoporphyrin ring to form heme. Thus, without
iron or if there is deficiency of iron there will be a problem in formation of heme wherein heme
is an another important component of hemoglobin.
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the
number of red blood cells or the amount of hemoglobin in the blood. Iron-deficiency anemia is usually
caused by blood loss, insufficient dietary intake, or poor absorption of iron from food. Sources of
blood loss can include heavy periods, childbirth, uterine fibroids, stomach ulcers. It can be diagnose
through blood test.

HbS :SICKLE CELL HEMOGLOBIN

Sickle-cell disease (SCD) is a group of blood disorders typically inherited from a person's parents.

The most common type is known as sickle-cell anemia (SCA). It results in an abnormality in the oxygen-
carrying protein haemoglobin (haemoglobin S) found in red blood cells. This leads to a rigid, sickle-like shape
under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A
number of health problems may develop, such as attacks of pain ("sickle-cell crisis"), anemia, swelling in the
hands and feet, bacterial infections, and stroke. Long term pain may develop as people get older. The average
life expectancy in the developed world is 40 to 60 years.

Sickle-cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene,
one from each parent. This gene occurs in chromosome 11. Several subtypes exist, depending on the
exact mutation in each hemoglobin gene. An attack can be set off by temperature changes,
stress, dehydration, and high altitude. A person with a single abnormal copy does not usually have symptoms
and is said to have sickle-cell trait. Such people are also referred to as carriers. Diagnosis is by a blood
test and some countries test all babies at birth for the disease. Diagnosis is also possible during pregnancy.
Symptoms of sickle cell anemia includes:

 excessive fatigue or irritability, from anemia

 fussiness, in babies
 bedwetting, from associated kidney problems
 jaundice, which is yellowing of the eyes and skin
 swelling and pain in hands and feet
 frequent infections
 pain in the chest, back, arms, or legs
 Hbs formation

THALASSEMIA

- Is a group of autosomal recessive genetic disorder characterized by a decreased or absent in the

synthesis of globin chain, leading to anemia and microcytosis.

CAUSE OF THALASSEMIA

Thalassemia autosomal genetic disorder where there is a defect in the genes that help in the
control of production of alpha-globin and beta-globin chain which are protein that constitutes
hemoglobin.

Thalassemia has 2 types depending on which of the globin chain are defective. Alpha
thalassemia is due to the deletion or mutation of the HBA1 and HBA2 gene in chromosome 16, which
leads to the decline in the production of alpha globin chain. Beta Thalassemia on the other hand is the
deletion or mutation of the HBB gene in chromosome 11 which consequently lead to the decrease in
production of beta-globin chains.

The 2 types of thalassemia can be further subdivided into subtypes depending on its genotype.
Alpha thalassemia is divided into 4 subtypes and Beta thalassemia into 3.

Table 1.
Types of Thalassemia Genotype
Alpha Thalassemia
- Silent Carrier (aa/a-)
- Alpha Thalassemia
Minor
 CIS Form (--/aa)
 TRANS Form (a-/a-)
 - Hemoglobin H (-a/--)
Disease
- Hemoglobin Bart (--/--)
Disease
Beta Thalassemia
) OR (B/ B0)
+¿¿
- Beta Thalassemia (B/ B
Minor
- Beta Thalassemia ( B0 /B +¿¿)
Intermedia
+¿ ¿
- Beta Thalassemia ( B+¿/ B ¿
) OR ( B0 /B 0)
Major

Clinical Manifestation differs depending on how many globin chains are mutated or deleted. In
Alpha Thalassemia if 3 of the genes (Silent Carriers) are present and not mutated this results to no
clinical manifestation. Mild microcytic anemia can be seen if there are only 2 of the alpha globin gene
present. Hemolytic anemia, splenomegaly, variable bone changes and iron overload is seen on
Hemoglobin H disease, which only has 1 globin gene. Hydrops Fetalis is the result if there is no alpha
globin gene present and can be seen in Hemoglobin Bart Disease.

Beta Thalassemia symptoms also varies depending on how many are mutated and the severity
of mutation. In B-Thalassemia Minor experience of minimal anemia can be observed but no treatment is
indicated. For B-Thalassemia Intermedia severe heterozygote can be a spectrum, most often does not
require chronic transfusion. For severe mutation like in B-Thalassemia Major also called Cooley’s Anemia
there is complete lack of beta protein in the hemoglobin that causes life-threatening anemia that
requires regular blood transfusion and extensive ongoing medical care.