HEMOGLOBIN AND MYOGLOBIN BIOCHEMISTRY

Introduction to Hemoglobin and Myoglobin

  • Both are oxygen-binding proteins.

  • Hemoglobin is found in blood; myoglobin is found in skeletal and cardiac muscle.

  • Different functions:

    • Hemoglobin: Oxygen transporter.

    • Myoglobin: Oxygen store.

Structural Characteristics

Myoglobin

  • Type: Globular protein.

  • Polypeptide Chain: 153 amino acids long.

  • Structure:

    • Composed of eight alpha helix sections (denoted A2H).

    • Amino acids in helices numbered (e.g., histidine F8).

Hemoglobin

  • Type: Globular protein (roughly spherical).

  • Polypeptide Chains: Tetramer composed of four chains (2 alpha + 2 beta).

    • Alpha Chains: 141 amino acids long.

    • Beta Chains: 146 amino acids long.

  • Each subunit of hemoglobin is similar to myoglobin's polypeptide chain.

Prosthetic Group

  • Common Prosthetic Group: Heme group (in both myoglobin and hemoglobin).

  • Composition:

    • Made up of a porphyrin ring and a central iron atom.

    • Each subunit of hemoglobin and myoglobin contains one heme group, located between E and F helices.

Binding Mechanism

  • The iron in the heme group binds to oxygen:

    • Iron Interactions: Can interact with six ligands.

      • Four from nitrogen atoms of the porphyrin ring.

      • Fifth from the imidazole side chain of histidine F8.

      • Sixth when oxygen is bound (tilted at 60 degrees).

  • Conformational change upon oxygen binding:

    • Iron shifts into the plane of the porphyrin ring, reducing distance above the plane from 0.055 nm to 0.026 nm.

    • Histidine F8 moves with the iron, triggering changes in hemoglobin's structure.

Hemoglobin Structure and Function

  • Four subunits form two dimeric halves: alpha1 beta1 and alpha2 beta2.

  • Subunit Interaction:

    • Alpha and beta subunits interact but do not interact with other similar subunits.

  • Types of Contacts:

    • Packing Contacts: No shift during conformational changes.

    • Sliding Contacts: Shift during these changes.

  • States of Hemoglobin:

    • T (Tense) Form: Oxygen only accessible to alpha chains.

    • R (Relaxed) Form: Allows oxygen binding to beta chains; interchain salt links and hydrogen bonds stabilize T form, broken in R form.

Myoglobin and Oxygen Release

  • Myoglobin becomes oxy-myoglobin upon binding oxygen and releases it during extreme oxygen deprivation (e.g., exercise).

Binding Curve Characteristics

  • Myoglobin shows classic Michaelis-Menten saturation behavior; hemoglobin shows a sigmoid-shaped curve.

  • Cooperativity:

    • Oxygen binding to one subunit enhances binding to others.

Hemoglobin Efficiency in Oxygen Delivery

  • In lungs:

    • Partial pressure of oxygen ~100 Torr, 98% bound to hemoglobin.

  • In capillaries:

    • Partial pressure of oxygen ~40 Torr, only 6% bound.

  • Difference due to Cooperativity:

    • 92% efficiency in delivering oxygen vs. potential 51% if interaction were hyperbolic.

Conclusion

  • Hemoglobin is approximately 1.8 times more efficient at oxygen delivery than it would be without cooperativity.