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Thai Le Phuong Anh OXYGEN-HEMOGLOBIN BINDING KINETICS Fall 2011 BiS 371 BioFluidics 1

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  • Thai Le Phuong Anh

    OXYGEN-HEMOGLOBIN BINDING KINETICS

    Fall 2011 BiS 371 BioFluidics

    1

  • Contents

    • General concepts : Oxygen-Hemoglobin binding.

    • Oxygen-Hemoglobin binding kinetics equations in three approaches.

    • Applications

    • Discussion & Summary

    • References

    2

  • 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.

    3

  • 4

  • • Ligand-Protein interaction

    •Cooperative binding.

    Oxygen-Hemoglobin

    binding

    5

  • Hemoglobin (tetramers) : 2 α chains and 2 β chains. Heme group containing iron.

    6

  • 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.

    7

  • Hill’s equation

    n=2.7

    8

  • Physical Meaning of the Equation

    What are the kinetics and equilibrium of Oxygen binding to Hemoglobin?

    9

  • The sequential oxygenation of the 4 heme groups

    10

  • K’1 as a function of Saturation.

    • •

    11

  • Applications

    Clinical diagnoses and therapeutic interventions:

    Altered oxygen transport pathways diseases treatment

    Efficient blood-gas exchangers design.

    Substitutes for blood development.

    12

  • Discussion

    The oxygen-binding properties of Hemoglobin are markedly affected by :

    • pH ( hydrogen ions).

    • Carbon dioxide (CO2)

    • DPG ( 2,3-diphosphoglycerate)

    • Temperature.

    13

  • Example : Human exercise

    Muscle tissue

    Reducing the affinity of oxygen for hemoglobin

    Supplying energy

    Lung

    Increasing the affinity of

    hemoglobin for oxygen

    Releasing CO2

    14

  • 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.

    15

  • 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.

    16

  • THANK YOU!!!

    17