(07) Hemoglobin 2

Introduction

• Topic: Mechanisms of cooperative binding in hemoglobin

• Learning Objectives:

  • Connect molecular changes during O2 binding to cooperative O2-binding properties of hemoglobin.

  • Explain the advantage of the sigmoidal shape of the oxygen-hemoglobin dissociation curve.

Structure of Hemoglobin

• Hemoglobin Composition:

  • Four subunits: 2 alpha subunits and 2 beta subunits (shown in blue).

  • Each subunit contains a heme group (green structures 1-4) for oxygen binding.

  • Overall capacity: Each hemoglobin can bind four O2 molecules.

• Significance of Hemoglobin:

  • Best-studied protein; easily isolated from red blood cells.

  • Model protein for understanding protein structure and function.

Oxygen Transport Characteristics

• Requirements of an Oxygen Transporter:

  • High Affinity in Lungs: Effective binding to oxygen when oxygen levels are high.

  • Low Affinity in Body: Rapid release of stored oxygen where it's needed.

• Role of Sigmoidal Shape:

  • Steep change in oxygen binding at specific partial pressures enhances rapid oxygen release.

  • Basis of cooperative binding mechanism.

Cooperative Binding Mechanism

• Affinity Changes:

  • Hemoglobin with no bound O2 has low oxygen affinity.

  • Binding of the first O2 increases the probability of further O2 binding due to increased affinity.

  • Three O2 binding increases affinity significantly—up to three times higher than the unbound state.

Detailed Structure of the Heme Group

• Heme Structure:

  • Composed of a porphyrin ring (carbons and nitrogens).

  • Iron at the center forms a reversible bond with O2.

• States of Heme Group:

  • Tense State (Bent): No O2 bound; ring configuration causes tension.

  • Relaxed State (Flat): O2 bound; iron is pulled to the center, leading to a straightened configuration.

Changes Induced by Oxygen Binding

• Transition from Tense to Relaxed State:

  • Oxygen binding alters the shape of the heme group, affecting its interaction with globin subunits.

  • Binding changes tertiary and quaternary structures of hemoglobin, facilitating further oxygen binding by increasing accessibility of the other heme groups.

• Importance of Subunit Interaction:

  • The cooperative nature is enhanced by the structure involving four heme groups interacting with their respective subunits.

Oxygen-Hemoglobin Dissociation Curve

• Sigmoidal Shape:

  • Represents binding efficiency at varying partial pressures of oxygen.

  • Effective loading (>95%) near the lung's partial pressures (10-15 kPa).

• Impact of Partial Pressure:

  • Significant release of oxygen occurs when partial pressure drops in the body (specific drops lead to major release).

  • At resting partial pressures of around 5-6 kPa, hemoglobin retains 70-80% of its bound oxygen, thus only releasing 20%, indicating less efficiency in oxygen transport in this range.

Conclusion and Preview

• Upcoming Topics: Solutions to the identified issues in oxygen transport efficiency will be discussed in the next session.

• Thanks for the attention and look forward to the next part.