HAEMOGLOBIN
DR NILESH KATE
MBBS, MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
At the End of Class
Haemoglobin
Structure, function,
variations
Derivatives, synthesis and
degradation of
hemoglobin.
Anemia – Types with
example, c/f , treatment
Haemoglobin
(C 712 H 1130 O 245 N 214 S 2 Fe) 4
HAEMOGLOBIN
It is a Red pigment
Present in RBC of Blood.
It is a conjugated protein,
& Chromoprotein.
It is made up of Iron and
Protein
It’s molecular weight is
68000.
Disadvantages if haemoglobin
present in plasma.
Increase viscosity.
Increase osmotic
pressure.
Rapid destruction by
reticuloendothelial
system.
Haemoglobinuria
( excretion through
kidney)
Sunday, February 14, 2016
NORMAL VALUES OF
HEMOGLOBIN
The Normal Hb level:
Fetus – 16-18 gm/dl
Newborn – 20-24
gm/dl.
Transfusion from
placenta
Haemoconcentration
NORMAL VALUES OF
HEMOGLOBIN
1 year – 10-12 gm/dl
Males - 14 – 17
gm/100ml
Females- 12 – 15
gm/100ml
Sunday, February 14, 2016
STRUCTURE OF HAEMOGLOBIN.
Iron containing pigment
called Haem attached
with protein – Globin.
Haeme is Iron –
porphyrin complex
called IRON-
PROTOPORPHYRIN IX.
Globin – Protein.
Sunday, February 14, 2016
STRUCTURE OF HAEME
IRON-PROTOPORPHYRIN IX.
IRON
Ferrous form (Fe2+).
Iron attached to
nitrogen atom of each
pyrrole ring.
On iron loose bond for
Oxygen
Carbon monoxide.
Sunday, February 14, 2016
STRUCTURE OF HAEME
IRON-PROTOPORPHYRIN IX.
Porphyrin nucleus.
4 Pyrrole Rings
(Tetrapyrrole)
Bridges – Methine (CH)
Side chains – 8
Methyl (CH3) - 4
Vinyl (CH.CH2) - 2
Propionic acid - 2
(CH2.CH2.COOH)
Sunday, February 14, 2016
Structure of Globin.
Made up of 4
polypeptide chains.
Globin is HbA
2 alpha chains ( ) –
141 amino acids
2 Beta chains ( ) – 146
amino acids.
Sunday, February 14, 2016
Attachment of Haeme to
Globin.
4 units of Haeme
attached to 1 unit of
Globin.
So 1 Haemoglobin
molecules contains 4
Iron Atoms which
carry 4 molecules of
oxygen.
Sunday, February 14, 2016
Synthesis of Hemoglobin
i) 2 succinyl – CoA + 2 glysine Pyrrole
ii) 4 Pyrrole Protoporphyrin IX
iii) Protoporphyrin IX + Fe2+ Heme
iv) Heme + Polypeptide Hemoglobin chain (α or β)
v) 2 α chains + 2 β chains Haemoglobin A.
Succinyl-CoA Glycine
Pyridoxal phosphate
αAmino -β-ketoadipic acid
ALA synthetase
α amino-δ-Laevulinic acid
ALA dehydrogenase.
Porphobilinogen
Protoporphyrin IX
ferrous
Haem globin
haemoglobin
Sunday, February 14, 2016
Factors controlling
Haemoglobin formation.
Role Of Proteins – First class proteins provide
amino acids.
Most imp – food of animal origin, liver, spleen,
kidney & heart
Intermediate value – muscles
Least – cereals, dairy products, veg & fruits.
Sunday, February 14, 2016
ROLE OF IRON.
Important for formation of Haeme part of
Haemoglobin.
Sources of iron – Dietary iron
Other sources – Iron released from degradation of
RBC.
Sunday, February 14, 2016
Role of other metals
Copper – Promotes Role of vitamins.
Absorption, Mobilization Vit B12, Folic acid help in
& Utilization of iron. synthesis of nucleic acid.
& vit C helps in
Cobalt – Increases
absorption of iron from
production of
gut. (Fe3+ to Fe2+)
Erythropoietin.
Role of bile salts.
Calcium – conserve iron Imp for proper
& subsequent utilization. absorption of copper &
nickel.
Sunday, February 14, 2016
Functions of Haemoglobin
Transport oxygen to tissues
Transport Co2 to lungs
Maintains acid base balance ( As a Buffer)
Haemoglobin – Oxygen
Binding.
O2 is attached with
haemoglobin reversibly at
6th covalent bond.
Oxygenation of 1st haem
increases affinity for 2nd
in turn 3rd & 4th.
Reason for O2-Hb
dissociation curve
Sigmoid shape.
Sunday, February 14, 2016
Oxygen – Haemoglobin
Dissociation curve.
As affinity of Hb for O2
falls graph shifted to
right.
As affinity of Hb for O2
rise graph shifted to
left.
H+ ion conc, Pco2
temp & 2,3-DPG
affects shift.
Sunday, February 14, 2016
Shift of Oxygen – Haemoglobin
Dissociation curve.
Shift to left. Shift to right.
Sunday, February 14, 2016
VARIETIES OF HAEMOGLOBIN.
Physiological. Pathological
Adult (Haemoglobinopathies)
Haemoglobin A -- Sickle Cell Haemoglobin.
4 polypeptide chains Hb C
2 α (alpha) & 2 β (Beta) Thallasemia.
Haemoglobin A2 -- 2 α
(alpha) & 2 δ (Delta)
Fetal.
FETAL HAEMOGLOBIN.
Present in fetal RBC &
disappear in 2-3 months
after birth.
Structure
4 polypeptide chains
2 α(alpha) & 2 γ (gamma)
Characteristics.
Affinity for oxygen – more
Resistance to action of alkalies
Life span – less.
Sunday, February 14, 2016
PATHOLOGICAL
(HAEMOGLOBINOPATHIES)
Sickle cell
haemoglobin.(HbS)
Substitution of Valine
for Glutamic Acid at 6th
position in beta chain.
When HbS is reduced (in
low O2 tension)
precipitate into crystals
in RBC changes shape
become Sickle shaped.
Sunday, February 14, 2016
EFFECTS OF SICKLE CELL SHAPE.
Less flexible – blockage
of microcirculation.
Increases blood
viscosity.
More fragile – More
Hemolysis – Anaemia.
Sunday, February 14, 2016
TREATMENT
Drugs – leads to
formation of HbF which
decreases
polymerization of
deoxygenated Hb.
Azacytidine
Hydroxyurea
Bone Marrow
Transplantation.
Sunday, February 14, 2016
Pathological
(Haemoglobinopathies)
Haemoglobin C. Thalassaemia
Defect in synthesis of
Similar to HbS but not polypeptide chain.
associated with Sickling. Types
Major
Other varieties are
Minor
HbE, HbI, HbJ, HbM
Sunday, February 14, 2016
DIFFERENCE IN THALASSAEMIA
MAJOR & MINOR.
β Thalassaemia Major β Thalassaemia Minor.
Less common More common.
Homozygous transmission Heterozygous
Complete absence of beta transmission.
chain synthesis. Partial Absense.
Anemia – moderate to Anemia- mild.
severe HbF – slightly elevated.
HbF – markedly increased Life span – comparatively
Life span – short longer.
Cooley’s Anaemia
Sunday, February 14, 2016
DERIVATIVES OF Hb
1. Hb + O2 HbO2 (Oxyhaemoglobin) Iron in ferrous state)
2. Hb + Cyanide Methaemoglobin Iron in ferric state.
3. Hb + CO2 Carbamino hemoglobin
4. Hb + CO Carboxy hemoglobin
5. Hb + H2S Sulphemoglobin.
6. Hb + Glucose Glycosylated ( attached to terminal
Valine)
FATE OF HAEMOGLOBIN
Tetra pyrrole straight chain with
Globin & Iron
Sunday, February 14, 2016
THANK
YOU
