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under the supervision of
Dr.YASSER AZIMASSISTANT PROFESSOR
DEPT.OF APPLIED CHEMISTRY,AMUYaseer.azim@gmail.com
ABU DARDAAbudarda.ms@amu.ac.inTEAMLEADER ZHCET-AMU
Myoglobin
Oxygen transport by Hb
Hemoglobin
Oxygen binding site
Co- opretivity Effect
Bohr Effect
Royal Mirage
Heme Protein
Heme protein
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ABOUT HEME1. Fe2+ + Protoporphyrin IX = HEME
2. Mb and Hb are “heme” proteins.
3. Bound to the protein permanently, either covalently or noncovalently bound or both.
4. Porphyrins are colored.
– Iron porphyrin gives red color to blood.
– Magnesium porphyrin gives green color
to plants.
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STRUCTURE OF HEMEPROTIEN
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SYNTHESIS OF HEME
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DEGRADATION OF HEME
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BIOLOGICAL FUNCTIONS OF HEMEPROTIEN
• Oxygen transport & store –Mb,Hb
• Catalysis- peroxidases, cytochrome c oxidase
• Electron transfer- cytochrome a, cytochrome
b, cytochrome c.
• Defense- catalase.
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DISORDERS
• Porphyria
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hemoglobinROYAL MIRAGE
• Hemoglobin is the basic metalloprotein that is present in
the red blood cells which are responsible for carrying
oxygen.
• Hb + 4O2 HbO8
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→
→
FUNCTION OF RBC
The main function of red blood cells-
Transfer of O2 from lungs to tissues.
Transfer of CO2 from tissues to lungs.
Each red blood cells has 640 million molecules
of Hb
Haemoglobin protien constituting 1/3 of the red blood
cells.
Molar mass of Hb-64500
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SYNTHESIS OF HEMOGLOBIN(Hb)Two Parts
HaemGlobin
HEAMo PROSTHETIC GROUP
o CONTAINING Fe+2 ION
GLOBINo HEME CONTAINING PROTEINS
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Hemoglobin is found exclusively in RBCs.
Its main function is to transport oxygen from lungs to the tissues
& carbon dioxide & hydrogen protons from tissues to lungs.
LUNGS TISSUES
Function of hemoglobin
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O2
CO2
→→
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Tetramer complex
Contain four globin molecules
Each globin contains 1 heme
Fe+2 ion in centre of heme
Fe+2 is known as feroheme
Anaemia symptoms
Loss of energy
Leg cramps
Difficulty concentrating
Rapid heart beat
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o Seafood
o Eggs
o Dried fruits
o Fruits
o Chocolate
o Meat
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OXYGEN TRANSPORT BY HAEMOGLOBIN
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Complex Protein containing HAEM (Iron)
1 molecule of Haem combines with 4 molecules of
Oxygen to form OXYHAEMOGLOBIN
Hb + 4O 2 → HbO8
Haemoglobin Oxygen Oxyhaemoglobin
The reaction is Reversible
→
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At lungs there is low (carbon dioxide) so Hb has a
greater affinity for Oxygen- so picks up more
Oxyhaemoglobin releases its oxygen where it is most
needed :to the actively respiring tissues
At the Tissues there is high (carbon dioxide) this reduces
Hb affinity for oxygen so it gives it up
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Oxygen dissociation curve of Oxyhaemoglobin
The curve shows that:
at relatively low oxygen concentrations there is uncombined haemoglobin in the blood and little or no oxyhaemoglobin, e.g. in body tissue
at relatively high oxygen concentrations there is little or no uncombinedhaemoglobin in the blood; it is in the form of oxyhaemoglobin, e.g. in the lungs
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1. Deoxygenated blood is transferred from heart to lungs
2. CO2 in blood is exchanged for O2 in lungs
3. The oxygenated blood is then carried by Haemoglobin from lungs to heart
4. Heart pumps out the oxygenated blood to arteries towards tissues
5. This Oxygen in blood is exchanged for CO2 in tissues
6. The deoxygenated blood is finally transferred to heart
The Circulatory system
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myoglobin
History facts
• First protein to have its three-dimensional structure
• In 1958, John Kendrew and associates successfully
determined the structure of myoglobin by high-
resolution X-ray crystallography.
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WHAT IS MYOGLOBIN?
• Myoglobin is an iron- and oxygen-binding protein
found in the muscle tissue of vertebrates in general
and in almost all mammals.
• Molecular weight-16,700 Daltons.
• Number of residues- 153
• Number of Polypeptide Chains-1
• Myoglobin forms pigments responsible for making
meat red.
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Structure & functions:
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• Myoglobin (Mb) is a single-chain globular protein
of 153 or 154 amino acids.
• Containing a heme (iron-containing porphyrin)
prosthetic group in the center.
• It has eight alpha helices and a hydrophobic core.ROYAL MIRAGE
Functions:• Stores oxygen in muscles.
• During starving condition it release oxygen to the
body tissues.
• Myoglobin forms pigments responsible for making
meat red.
• High concentrations of myoglobin in muscle cells
allow organisms to hold their breaths longer.
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Role in disease:
• Rhabdomyolysis
• Acute renal failure
• It is a sensitive marker for muscle injury.
• it is a potential marker for heart attack in patients
with chest pain.
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OXYGEN BINDING SITE
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WHAT IS OXYGEN BINDING?
• Binding of Oxygen ( O2) to Heme proteins i.e., haemoglobin, myoglobin & hemocyanin etc.
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HAEMOGLOBIN & MYOGLOBIN• Haemoglobin & myoglobin are oxygen transporter and
storage proteins.
• Haemoglobin is tetrameric while Myoglobin is
monomeric.
• Hb: two α chains of 141 residues & two β chains of 146
residues.
• Hb: Molecular weight- 64,000 daltons.
• Mb: 153 amino acids, Molecular weight-17,700 daltons.
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• Fe in the heme group is the site for oxygen binding.
• Hb forms a reversible bond with the Oxygen.
• When Oxygen binds Ferrous state ( Fe+2) changes to Ferric state (Fe +3).
• Single Hb unit can bind 4 Oxygen molecule.
• Binding of Oxygen with Hb is called cooperative binding.
HOW OXYGEN BINDS WITH HEMOGLOBIN?
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• Its binding is similar to hemoglobin.
• Fe in Mb is in ferrous state- that binds oxygen.
• Oxidation of Fe yields 3+ charge i.e., ferric state-
metmyoglobin does not bind oxygen.
• One Mb unit can bind only one Oxygen molecule.
• Its binding is called non-cooperative binding.
BINDING OF OXYGEN WITH MYOGLOBIN
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• Hb undergoes a conformational changes on binding
Oxygen.
• Two major conformation of Hb-
R (relaxed) and T( tense) state.
• T- state is more stable (deoxyhemoglobin).
• Binding O2 to hemoglobin subunit in T-state triggers
a change in conformation to R-state.
CONFORMATIONAL CHANGES IN Hb
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• Heme group is non-planar in deoxygenated state.
• Oxygen binding pulls the Fe into the heme plane.
• Fe pulls its His F8 ligand along with it.
• In oxygenated state, heme group is planar.
• The F helix moves when oxygen binds.
• Total movement of Fe is 0.029 nm-0.29 Å.
GEOMETRICAL CHANGES
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Cooperativity of Haemoglobin
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What is cooperativity effect?
The phenomenon where the addition of oxygen to one Hemegroup facilites its addition to the other Heme groups of Haemoglobin is known as Cooperativity Effect
The cooperativity of O2 binding to Haemoglobin influences how much of the blood O2 is delivered to any particular tissue
This property is called an OXYGEN DISSOCIATION CURVE
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Shows the amount of O2 that is
bound to Haemoglobin (Y-axis)
as a function of partial pressure
of O2 in the blood plasma (X-
axis)
Because of the cooperativity
this dissociation curve is
S-shaped.
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• Successive oxygenation reactions of haemoglobin are as follows:
Hb + O2 𝑯𝒃𝒐𝟐Hbo2 + O2 Hb(O2)2
Hb(O2)2 Hb(02)3
Hb(O2)3 + O2 Hb(O2)4
Overall rate constant
K = [𝑯𝒃 𝑶
𝟐 𝟒]
𝑯𝒃 𝟎𝟐𝒏 ; K = Binding constant & n = Hill constant
Value n=4 represents MAXIMUM COOPERATIVITY EFFECT
Binding constant of oxyhaemoglobin
K1
K2
K3
K4
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→→→
→→→→→
Explanation of Cooperativity Effect
In deoxyhaemoglobin,the heme group is out of the plane and
iron is in +2 oxidation state and in high spin
Oxygen binds to the heme group through vacant sixth
coordination site and iron is in +3 oxidation state and in
low spin
These changes in the heme unit due to its coordination with
O2 trigger the cooperativity phenomenon
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Bohr effect
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About Christian Bohr
Christian Harald Lauritz Peter Emil Bohr
• 1880 MS from University of Leipzig
•1886 Prof. university
of Copenhagen
•1891 Dead space
•1903 Bohr effect
•Danish physiologist
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•The effect of pH and CO2
concentration on the binding and
release of oxygen by hemoglobin
•Lowering the pH
•Raising the partial pressure of co2
•The release of O2 from oxyhemoglobin
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BOHR EFFECT
Frac
tio
nal
sat
ura
tio
n
Oxygen partial pressure
At lower pH, His 146 is protonated which favours
the deoxyHBconformation thereby
leading to release of O2
Carbamate ROYAL MIRAGE
O2O2
O2O2O2
O2O2
O2
Raising partial pressure of carbon dioxide
Lowering pH
Oxyhemoglobin Deoxyhemoglobin
Peripheral tissues
O2
2H+ + 2HCO3- 2H2CO3
2CO2 + 2H2O
Carbonic anhydrase
2CO2 + 2H2O
Exhaled
Carbonic anhydrase
2HCO3- + 2H+
4O2
Lungs
2H2CO3
Hb + 4O2
Hb + 2H+
(buffer)
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