Lecture on Hemoglobin and Myoglobin

Overview

• Hemoglobin and Myoglobin: Two oxygen-binding proteins.
  • Hemoglobin: Found in blood, functions as an oxygen transporter.
  • Myoglobin: Abundant in skeletal and cardiac muscle, functions as an oxygen store.

Structure

• Myoglobin:
  • Globular protein made of a single polypeptide chain (153 amino acids).
• Hemoglobin:
  • Also a globular protein, spherical, tetrameric structure.
  • Composed of four polypeptide chains (alpha-2, beta-2 type):
    • Two identical alpha chains (141 amino acids each).
    • Two identical beta chains (146 amino acids each).

Polypeptide Chains

• Both myoglobin and hemoglobin polypeptide chains consist of eight alpha-helix sections (A to H).
• Connecting regions named after their connecting helices (e.g., AB region, BC region).
• Amino acids in each helix are numbered (e.g., Histidine F8).

Prosthetic Group

• Heme Group: Prosthetic group in both myoglobin and hemoglobin.
  • Composed of a protoporphyrin ring and central iron atom.
  • Iron can interact with six ligands:
    • Four from nitrogen atoms of pyrroles in the porphyrin ring.
    • Fifth from the imidazole side chain of histidine F8.
    • Sixth ligand is oxygen, tilted at 60 degrees.

Oxygen Binding and Conformational Changes

• Iron Binding:
  • Iron initially 0.055 nm above the porphyrin plane.
  • Binding of oxygen draws iron into the plane (0.026 nm above).
  • Triggers conformational changes:
    • In hemoglobin, increases affinity for adjacent heme groups.

Hemoglobin Structure and Interactions

• Composed of two dimeric halves (alpha-1, beta-1 and alpha-2, beta-2 pairs).
• Types of Contacts:
  • Packing contacts: Do not shift during conformational changes.
  • Sliding contacts: Shift during conformational changes.

Conformational States

• Two states: T (Tense) and R (Relaxed).
  • T Form:
    • Oxygen binds to alpha chains only due to steric hindrance.
  • R Form:
    • Hemoglobin stabilized in this conformation after oxygen binds.

Myoglobin vs. Hemoglobin

• Myoglobin:
  • Binds oxygen and becomes oxymyoglobin.
  • Releases oxygen during extreme oxygen deprivation.
• Hemoglobin:
  • Cooperative binding of oxygen.
  • Sigmoid binding curve (as opposed to hyperbolic):
    • Cooperativity enhances oxygen binding at one subunit causing increased oxygen affinity at others.

Oxygen Binding Efficiency

• Partial Pressure:
  • Lungs: 100 Torr (98% hemoglobin bound to oxygen).
  • Tissues: 40 Torr (68% hemoglobin releases oxygen).
• Efficiency:
  • Cooperative binding makes hemoglobin 1.8 times more efficient than if it displayed hyperbolic behavior.

Conclusion

• Hemoglobin's cooperative binding significantly enhances its oxygen transport capability.