Lecture Notes on Allosteric Effectors of Hemoglobin

Introduction

• Hemoglobin is an allosteric protein
  • Has two receptor sites: one for ligand (oxygen) and one for allosteric effectors
  • Allosteric effectors induce conformational changes affecting ligand affinity
    • Positive effectors increase affinity
    • Negative effectors decrease affinity
• Oxygen is the ligand for hemoglobin
  • Positive allosteric effectors stabilize the relaxed (R) state with higher oxygen affinity
  • Negative allosteric effectors stabilize the tense (T) state with lower oxygen affinity

Types of Allosteric Effectors

1. Homotropic Effectors

   • The ligand acts as an effector (e.g., oxygen)
   • Binding of oxygen at one site increases affinity at other sites
   • Oxygen is a positive homotropic effector

2. Heterotropic Effectors

   • Effectors different from the ligand (e.g., protons, CO2, 2,3-BPG)
   • Typically decrease oxygen affinity (negative effectors)

Heterotropic Effectors of Hemoglobin

Protons (H+)

• Released by actively metabolizing tissues
• Bind to hemoglobin, stabilizing the T state
• Protonation of histidine forms ionic bonds with aspartate, enhancing the T state
• Low pH (acidosis) decreases oxygen affinity, shifting the oxygen saturation curve to the right

Carbon Dioxide (CO2)

• 70% hydrates to form carbonic acid and bicarbonate, promoting H+ binding
• 20% forms carbaminohemoglobin at the amino termini of hemoglobin
• Stabilizes the T state
• High CO2 levels decrease oxygen affinity, shifting the curve to the right (Bohr effect)

2,3-Bisphosphoglycerate (2,3-BPG)

• Synthesized in red blood cells from glycolytic intermediates
• Binds to deoxyhemoglobin, stabilizing the T state
• Increased production under low oxygen conditions (e.g., high altitude)
• High 2,3-BPG decreases oxygen affinity, shifting the curve to the right

Summary

• Heterotropic effectors (H+, CO2, 2,3-BPG) decrease hemoglobin's affinity for oxygen
• Conditions that shift the hemoglobin saturation curve to the right include:
  • High H+ concentration (acidosis)
  • High CO2 levels
  • High 2,3-BPG levels
• Rightward shifts are physiologically beneficial as they enhance oxygen delivery to tissues

Conclusion

• Understand how different conditions and effectors influence hemoglobin’s oxygen affinity
• Rightward shifts indicate decreased affinity and enhanced oxygen delivery

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• For further details, refer to previous materials on hemoglobin conformations and structural rules.