oxygen-hemoglobin binding kineticsnanobio.kaist.ac.kr/lectures/bis_371/notes2011/phuong.pdf ·...
TRANSCRIPT
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Thai Le Phuong Anh
OXYGEN-HEMOGLOBIN BINDING KINETICS
Fall 2011 BiS 371 BioFluidics
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Contents
• General concepts : Oxygen-Hemoglobin binding.
• Oxygen-Hemoglobin binding kinetics equations in three approaches.
• Applications
• Discussion & Summary
• References
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General Concepts
The transition from anaerobic to aerobic life in evolution uncovered a rich reservoir of energy.
Oxygen is required in metabolic reactions that produce energy for cells.
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• Ligand-Protein interaction
•Cooperative binding.
Oxygen-Hemoglobin
binding
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Hemoglobin (tetramers) : 2 α chains and 2 β chains. Heme group containing iron.
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Cooperative Oxygen-Hemoglobin Binding
Why oxygen binding to hemoglobin is called as cooperative?
The binding of one oxygen molecules to one heme group facilitates the binding of subsequent oxygen molecules to the other heme group.
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Hill’s equation
n=2.7
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Physical Meaning of the Equation
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What are the kinetics and equilibrium of Oxygen binding to Hemoglobin?
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The sequential oxygenation of the 4 heme groups
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K’1 as a function of Saturation.
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Applications
Clinical diagnoses and therapeutic interventions:
Altered oxygen transport pathways diseases treatment
Efficient blood-gas exchangers design.
Substitutes for blood development.
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Discussion
The oxygen-binding properties of Hemoglobin are markedly affected by :
• pH ( hydrogen ions).
• Carbon dioxide (CO2)
• DPG ( 2,3-diphosphoglycerate)
• Temperature.
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Example : Human exercise
Muscle tissue
Reducing the affinity of oxygen for hemoglobin
Supplying energy
Lung
Increasing the affinity of
hemoglobin for oxygen
Releasing CO2
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Summary
• Cooperative Oxygen-Hemoglobin binding significantly increase the efficiency of Oxygen transportation.
• Cooperative binding can be potentially explained by three approaching models.
• Oxygen-Hemoglobin can be sensitive to some environmental factors.
• Such hemoglobin molecules are characterized by poor oxygen binding, releasing and low solubility leading to the destruction of red blood cells.
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References
• George A.Truskey, Fan Yuan, David F. Katz, Transport Phenomena in Biological systems.2nd ed. 2010, Pearson Prentice Hall.
• Berg, Tymoczko, Stryer, Biochemistry. 6th ed. 2006, Freeman.
• Quentin H.Gibson,”The contribution of the α and β chains to the Kinetics of Oxygen Binding to and Dissociation from Hemoglobin.”Proc.Natl.Acad.Sci.,1973. 70: pp.1-4
• Meldon, J.H.,”Blood-gas equilibria,kinetics and transport.” Chem.Eng.Sci.,1987. 42:pp.199-211.
• George Ilgenfritz,Todd M.Schuster.,”Kinetics of Oxygen binding to human hemoglobin.”J.Biol.Chem.,1972. 249:pp.2959-2973.
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THANK YOU!!!
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