Heme Chemistry

Heme Chemistry
Hemoproteins:
– They are proteins containing iron in the form of
heme.
– Heme is formed of ferrous iron attached to
protoporphyrin ring.
– Heme is a ferrous (FeII or Fe2+) protoporphyrin IX
(III).
– Hemoproteins include: hemoglobin, myoglobin,
cytochromes, catalase, peroxidase, nitric oxide
synthase and tryptophan pyrrolase.
 Hemoglobin
• Site: red blood cells,
• Function: is to transport oxygen
from the lungs to every tissue in the
body and remove CO2 from them.
 Structure of hemoglobin:
• Hemoglobin is a conjugated protein formed
of heme attached to globin protein.
• – The globin part of the normal adult
hemoglobin (HbA) is a tetramer, i.e. formed
of 4 polypeptide chains, two α-chains and
two β chains (α2β2).
• – Each polypeptide chain holds a heme
group, i.e. 4 heme groups and 4
polypeptide chains per one hemoglobin
molecule.
• – Hb/oxy-Hb system acts as buffer in RBCs
for H2CO3.
 Types of normal human hemoglobin:
1.HbA1: It is the commonest normal adult hemoglobin, formed of two α- and two
β chains (α2, β2).
2.HbA2: It is minor adult hemoglobin, formed of two α- and two δ chains (α2, δ2).
3.HbA3: It is an altered form of HbA1, present in old RBCs.
4.HbF: It is a human fetal hemoglobin, formed of two α- and two γ chains (α2 γ2).
5.Embryonic Hb: It is present in the first three months of intrauterine life, formed
of two α- and two ε-chains (α2ε2).
6.HbA1c: It is a glycosylated Hb and measuring its level in blood is considered a
good test for follow up of diabetic patients.
 Derivatives of hemoglobin:
1. Oxy-Hb: Oxygen binds to Hb without oxidation of ferrous (Fe++) to
ferric (Fe+++).
2. Carbamino-Hb: CO2 binds to Hb.
3. Carboxy-Hb: Carbon monoxide binds to Hb.
4. Met-Hb: The ferrous (Fe++) is converted to ferric (Fe+++) due to
oxidizing agents. N.B. both oxy-Hb and carbamino-Hb are normal
derivatives of hemoglobin.
 Abnormal types of hemoglobin
• 1. HbS: – It is a genetic disease caused by replacement of the
glutamic acid at position 6 of βchain by valine. This causes sickle-cell
anemia. In this disease, the RBCs are sickled in shape and their life
span is decreased.
• 2. HbM: – It is a genetic disease caused by replacement of the
proximal or distal histidine of α- or β-chains by tyrosine. There is a
marked decrease in oxygen binding capacity and the patient suffers
from hypoxia .
• 3. HbC: – It is a genetic disease caused by replacement of glutamic
acid at position 6 of βchain by lysine. This produces reduction of the
life span of RBCs and mild, chronic hemolytic anemia.
4. α-Thalassemias:
• The synthesis of α-globin chains is absent or decreased.
• As each individual contains four copies of the α-globin gene, there are
several levels of α-globin chain deficiencies:
 Silent carrier: If one gene is defective, no physical manifestations.
 α-Thalassemia trait: if two genes are defective; suffer from mild anemia.
 α-Thalassemia major: if three genes are defective; suffer from moderate
to severe anemia.
 Homzygous α-thalassemia: The four genes are defective; usually die
intrauterine or shortly after birth (hydrops fetalis).
5. β-Thalassemias:
– The synthesis of β-globin chains is absent or decreased whereas α-globin
chain synthesis is normal.

There are only two copies of the β-globin gene.

Therefore, individuals have either

β-thalassemia trait (β-thalassemia minor) if they have only one defective β-
globin gene,
or β-thalassemia major if both genes are defective. The fetus appears normal
at birth because the HbF is formed at a normal rate (manifestations of
hemolytic anemia appears later after birth).
 Immune System
• If you inoculate a foreign substance into an animal, then after a few weeks
a protein will probably appear in the blood, this protein will bind
selectively to the foreign substance that provoked its appearance. – The
protein produced is known as antibody or immunoglobulin (Ig), and the
substance that provoked its production is called an antigen.
 Immune response:
• A. The primary response: – If an antigen
enters the blood, antibodies specific for this
antigen will appear in the blood, these
antibodies are IgM, which will reach a peak
within a week, then start to decline and be
replaced by IgG.

• B. The secondary response: – If a booster

dose of the antigen is given, a rapid and
massive increase in the amount of IgG occur
and persist for extended period.
 Structure of Immunoglobulin
• A typical antibody is a Y-shaped molecule consisting of two identical light
chains and two identical heavy chains linked by disulfide bonds. Each
• Light chain and each heavy chain has a variable region (V) and a constant
region (C).
• The variable region, which is at the prongs of the Y, binds to the antigen.
• The constant region, towards the stem of the Y, activates phagocytes and
complement, the parts of the immune system that destroy antibody-bound
antigen.
 Immunoglobulin classes:
1. Immunoglobulin G (IgG):
the most abundant Ig in blood,
the main one in 2ry immune response.
the only Ig that can cross the human placenta from mother to fetus, giving
passive protection to the baby for the first few months of its life.
2. Immunoglobulin A (IgM):
– The main in secretions:
 in
GIT,
respiratory tract,
colostrum and
 milk.
– The body makes more of it than any other Ig class, but most of what is made
is quickly excreted, rather than remain in the blood.
3. Immunoglobulin M (IgM):
It is largely confined to blood

the first 1ry immune response and the first to disappear again.
4. Immunoglobulin E (IgE):
– It occurs on the surface of mast cells and triggers inflammatory reactions
when it detects antigens.
5. Immunoglobulin D (IgD):
– It occurs on the surface of the precursors of antibody-forming cells (B
cells), where
it may act as a receptor by which the cell recognizes antigen.

In B cells, the function of IgD is to signal the B cells to be activated. By being

activated, B cells are ready to take part in the defense of the body as part of
the immune system. During B cell differentiation, IgM is the exclusive
isotype expressed by immature B cells.