Transcript Hemoglobin

Hemoglobin (Hb)
Hb is found in RBCs its main function is to transport O2 to tissues.
Structure: 2 parts : heme + globin
Globin: four globin chains (2 α and 2β).
Heme: Porphyrin ring with central iron. Iron is the site of attachment
with O2.Iron must be in ferrous state to bind oxygen and form
oxy Hb. Ferric state can’t carry oxygen and it form
methemoglobin (MetHb)
There are 4 heme groups each attached to one globin chain. So one Hb
molecule can carry up to 4 O2 molecules and in this case called oxyHb.
(R form). When oxygen is
released into tissues, Hb will
Be deoxy Hb (T form).
Types of Hb:
Hb A or HbA1 (Adult Hb): is the normal Hb in adults represents about
97% of total Hb. it is composed of 2 α and 2 β chains.
HbA2: minor adult Hb, comprised 3% of normal adult Hb. Composed
of 2 α and 2 δ chains
HbF(fetal Hb, α2γ2 Hb): is the main Hb during fetal life and in
newborns then disappear gradually where it is replaced by Hb A shortly
after birth.
It is composed of 2α and 2 γ chains.
Hb F has greater affinity for O2 than HbA so ensure O2 transfer from
maternal circulation to fetus RBCs through placenta (through umbelical
vein).
Note: The overall hemoglobin composition in a normal adult is
approximately 97.5% HbA1, 2% HbA2 and 0.5% HbF.
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.
Such sickled cells
frequently
block
flow of blood in
narrow capillaries
and block blood
supply to tissue
(tissue
anoxia)
causing pain and
cell death.
Note: The life time
of erythrocyte in
sickle cell is less
than
20
days,
compared to 120
days for normal
RBCs.
Patients may be :
Heterozygotes
(HbAS):
There are two copies of the
gene that synthesize β
globin chain. In Hb AS,
mutation occurs only in one
copy of the gene so patients
have some normal Hb A.
These patients have sickle
cell trait with no clinical
symptoms and can have
normal life span.
Or: Homozygotes (Hb SS):
mutation occurs in both
copies of gene that synthesize
β-globin chain with apparent
anemia and its symptoms
2- Hb C disease: Like HbS, Hb C is a mutant Hb in
which glutamic acid in 6th position of β-chain is replaced
by lysine. RBCs will be large oblong and hexagonal.
The heterozygous form (HbAC) is asymptomatic.
The homozygous form (Hb CC) causes anemia, tissue
anoxia and severe pain.
3- Thalassemia: A group of genetic diseases in which a defect occur in
the rate of synthesis of one or more of Hb chains, but the chains are
structurally normal. This due to defect or absence of one or more of
genes responsible for synthesis of α or β chains (see Fig.) leading to
premature death of RBCs.
Types:
β -thalassemia: When synthesis of β chains is decreased or absent.
There are two copies of the gene responsible for
synthesis of β chains. Individuals with β globin gene defects have either :
-β -thalassemia minor (β –thalassemia trait) : when the synthesis of
only one β –globin gene is defective or absent. Those individuals make
some β chains and usually not need specific treatment.
-β -thalassemia major (Cooley anemia): if both genes are defective.
-Babies will be severely anemic during the first or second year of life and
so require regular blood transfusion. Bone marrow replacement is more
safe treatment (why?).
Genes responsible for synthesis of Hb molecule (α and β globin
chains)
-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 copy of the genes is absent
ii- α-thalassemia trait: if two copies of genes are absent
iii- Hb H disease: if 3 copies of genes are absent, 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) which bind O2
but does not deliver it to tissues.
iv- Hydrops fetalis: when all 4 copies of α globin genes are absent. It
causes fetal death (babies with this disorder usually die before or
shortly after birth) because α globin chains are required for synthesis
of Hb F.
The inheritance of alpha thalassemia is complex because each parent
potentially passes two of their four alpha globin genes to the offspring
Myoglobin:
- It
is a heme protein formed of one heme molecule
attached to one globin chain (monomer). It can carry one
molecule of oxygen that is bound to iron (ferrous state)
- it is a monomer globular protein
- its secondary structure contains high proportion (80%)of α
helix. It contains 8 α-helix
- It is found only in red skeletal muscles and cardiac muscle.
It gives their tissues their characteristic red color.
-Myoglobin serves as an intracellular storage site for
oxygen. During periods of oxygen deprivation
oxymyoglobin releases its bound oxygen which is then used
for metabolic purposes within the cell.
-So, It is used to store oxygen rather than transport it.
Clinical significance of myoglobin:
-Myoglobin concentration is increased in blood in:
disease called myocardial infarction
and in case of muscle trauma and myopathies i.e. in any case related to
damage of muscle tissues.
NB: Hb and myoglobin are hemoprotein that have ability to bind
oxygen
Q:
Certain amino acids are not part of primary structure of proteins but
are synthesized after translation by certain modification. In
collagen, which amino acid is not a part of the pimary structure of
the protein?
a) proline
b) glycine
c) hydroxyproline
d) lysine
Question II: Give the name of:
1- Three plasma proteins with transport function
2- A protein with storage function:
3- Globular protein with a quaternary structure:
4- Fibrous protein with a quaternary structure: