(08) Hemoglobin 3

Overview of Hemoglobin Function

• Focus: How hemoglobin's O2 affinity changes during transport between lungs and body.

• Learning Objectives:

  • Explain decrease in O2 affinity in the body.

  • Summarize effects of pH, PCO2, temperature, and 2,3-BPG on hemoglobin structure.

  • Explain inefficiency of human hemoglobin at high altitudes.

Oxygen-Hemoglobin Dissociation Curve

• Sigmoidal curve illustrates how effectively hemoglobin loads oxygen in the lungs.

• In the body, typical PO2 leads to only 20-30% oxygen release from hemoglobin, indicating limited transport effectiveness.

Factors Influencing Hemoglobin Affinity

Increased PCO2

• Higher CO2 levels lead to:

  • Right-shift of dissociation curve (lower affinity for oxygen).

  • Easier oxygen release in high CO2 environments.

Decreased pH

• Lower pH (more acidic) results from:

  • Greater proton concentration.

  • Right-shift of the curve, promoting oxygen release.

Increased Temperature

• Higher temperatures (as in active muscles) encourage:

  • Right-shift in Hb-oxygen binding curve.

  • Facilitation of oxygen release due to lower affinity.

Comparative Conditions: Lungs vs. Body

• In Lungs:

  • Lower PCO2, higher pH (due to CO2 exhalation).

  • Higher affinity for oxygen (left-shift of the curve).

• In Body:

  • Higher PCO2, lower pH, higher temperature.

  • Lower affinity for oxygen (right-shift of the curve).

• Overall, hemoglobin transitions from high affinity (lungs) to low affinity (body), promoting efficient gas exchange.

Role of 2,3-BPG

• Byproduct of glycolysis in red blood cells that influences long-term oxygen affinity.

• Adjustments to 2,3-BPG levels occur slowly (days).

• At altitudes (2000-3000 meters), increased 2,3-BPG helps improve hemoglobin function over time.

Molecular Mechanisms Affecting Hemoglobin Structure

Influence of 2,3-BPG

• Binds at the center of hemoglobin subunits:

  • Stabilizes the tense (T) state of hemoglobin, leading to reduced oxygen affinity.

Influence of PCO2

• CO2 binds to N-terminal of subunits:

  • Forms carbamate, releasing protons, increasing affinity for the tense state.

Influence of pH

• Protons interact with specific amino acids (histidine 146), leading to:

  • Stabilization of interactions between subunits, promoting low affinity (tense state).

Conclusion: Structural Changes to Function

• Charged molecules (CO2, protons, 2,3-BPG) alter hemoglobin's structure significantly, affecting oxygen transport efficiency.

• Single amino acid changes in hemoglobin can have drastic effects on functionality, particularly the positioning of charged vs. hydrophobic amino acids.