PROTEINS i. FIBROUS PROTEINS Collagen Elastin Keratin ii. GLOBULAR PROTEINS Myoglobin Hemoglobin.
Hemoglobin, an AllostericProtein. Hemoglobin vs Myoglobin Hemoglobin (Hb): - found in red blood...
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Transcript of Hemoglobin, an AllostericProtein. Hemoglobin vs Myoglobin Hemoglobin (Hb): - found in red blood...
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Hemoglobin, anAllostericProtein
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Hemoglobin vs Myoglobin
Hemoglobin (Hb):
- found in red blood cells
- responsible for transport of O2 from
lungs to cellular tissue
- transport of some CO2 and H+ back to lungs
Myoglobin (Mb):
- Located in Muscles
- Aids O2 diffusion to tissue
- Acts as O2 storage reservoir
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Protein
HemeHistidines
MyoglobinBinds O2 in muscles
A complex monomeric proteinwith 1o, 2o and 3o structure
Bundle of 8 a-helicesIn 3o structure
The interior is largelyHydrophobic withVal, Leu, Ile, Phe, Met
Figure 9.3
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Red blood cells (erythrocytes)
Each cell contains approximately 300 million hemoglobin molecules.
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Hemoglobin is tetrameric andcarries oxygen in the blood
A complex tetrameric proteinwith 1o, 2o, 3o and 4o structure
Figure 9.6
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Fe(II)-protoporphyrin IX hemethe pyrrole rings provide 4 of the 6 ligands that bind to the Fe(II).
Heme, a Prosthetic Group in myoglobin and hemoglobin
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The reversible binding of oxygen to heme
Oxymyoglobin has six ligands boundDeoxymyoglobin has five ligands bound
Proximal His
Distal His
Same for oxy- and deoxyhemoglobin
Myoglobin is monomeric and binds O2 in muscles
Heme
Histidines
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Oxygen binding curves of hemoglobin and myoglobin
Y = Fractional oxygen saturation of myoglobinMb = Concentration of myoglobin molecules without bound oxygenMbO2 = Concentration of myoglobin molecules with bound oxygenMb + MbO2 = total concentration of myoglobin molecules
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Equilibrium reversible binding of OxygenFigure 9.1
Mb + O2 MbO2
Hb + 4 O2 Hb(O2)4
O2 binding to Mbhas a hyperbolic curve
O2 binding to Hbhas a sigmoidal curve
The larger value of pO2 at Y=0.5 means lower affinity for oxygenO2 binding to Hb
must be cooperative pO2(0.5) = 2.8 torr (Mb)pO2(0.5) = 26 torr (Hb)
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Cooperatively helps to release O2 at location of tissue cells
Both Mb and Hbare saturated with O2
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Cooperatively helps to release O2 at location of tissue cells
At the tissue cells 93% of Mb is MbO2, BUT only ~32%of Hb binding sites have O2 bound
What causes this binding cooperatively??
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Oxygen binding induces protein conformational changesFigure 9.4
Blue = HbRed = HbO2
The Fe2+ is pulled into theplane of the heme porphyrin
Movement of the proximal His induces a change in the a subunitCausing a change in the b unit
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Oxygen binding induces protein conformational changesFigure 9.7
Grey structure
Red structure
This in turn changes the whole quaternary structure
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Oxygen binding induces protein conformational changesFigure 9.8
The binding of the other three subunitsdramatically increases
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Hemoglobin is an allosteric protein
- The binding of O2 can be affected by allosteric interactions or binding of aallosteric effector
- The allosteric effector binds reversibly at a site that is different from thefunctional site (e.g. O2 binding site).
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Binding of 2,3-BPG alters Hb affinity for O2
Less O2 is bound to Hb near tissue cellswith 2,3-BPG bound.
2,3-BPG stabilizes the deoxyHb.
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[H+] and CO2 can bind to Hemoglobin and decrease oxygen affinityThe Bohr Effect
As the pH decreases hemoglobinhas lower affinity for O2.
The buffering of bloodand HbO2 affinity are directly related.
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The drop in pH favors the deoxyHb structure via non-covalent interactions
Drop in pH caused increasein His 146 protonation.
A new hydrogen bond is formed
Figure 9.19
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The presence of CO2 alsoalters O2 binding affinity.
The Bohr effect andCO2 combined areimportant in exertion or exercising.
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Hemoglobin (Hb) & buffering of blood and O2 transportAt Tissue
Tissue cells Plasma Red Blood Cell
C6H12O6 + O2
H2O + CO2 CO2
diffusionCO2 + H2O
Carbonicanhydrase
H2CO3
HCO3- + H+HCO3
-
(buffer)
Cl- Cl-
+ HbO2
H+HbO2 (low affinity)O2 + H+HbO2
(Delivery to cells)
Figure 9.17and 9.21
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Hemoglobin (Hb) & buffering of blood and O2 transportAt Lungs
Lungs Plasma Red Blood Cell
CO2 CO2
diffusion
Carbonicanhydrase
H2CO3 + HbO2 (high affinity)
HCO3- HCO3
-
Cl- Cl-(low affinity)
O2 O2 O2 + H+Hb
H+HbO2
H2O + CO2
exhale out
Acidosis: pH
Alkalosis: pH
Figure 9.17and 9.21
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How is Hemoglobin effected by genetics and environment?
Read about sickle cell anemia and malaria and geese livingnear Mt. Everest: Clinical Ins. Pg 147
Fetal RBC have greater O2 affinity than Maternal RBC….why?Clinical Ins. Pg 146
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Assignment
Read Chapter 9Read Chapter 10