Myoglobin and Hemoglobin: Structure and Function

Myoglobin and Hemoglobin

Overview of Hemoglobin Functions

• Transport of H+ and CO2: Hemoglobin not only carries oxygen ($O2$) but also transports H+ ions and carbon dioxide ($CO2$), which are products of cellular respiration.
• Carbonic Anhydrase Role:
  • Catalyzes the reaction:
    CO2 + H2O ⇌ H2CO3 ⇌ H^+ + HCO3^-
  • This reaction helps maintain acid-base balance during gas exchange.

Biological Context

• Influence of Metabolism on pH:
  • Actively metabolizing tissues produce H+, lowering blood pH near tissues compared to lungs.
  • The increased concentration of H+ enhances the release of oxygen from hemoglobin (Hb).

Bohr Effect

• Definition: Describes how lower pH and higher carbon dioxide concentration lead to decreased affinity of hemoglobin for oxygen, promoting oxygen delivery to tissues.
• Mechanism:
  • H+ ions bind to hemoglobin, stabilizing the T (tense) state of the molecule, which leads to the release of bound $O_2$.
  • Protonation of His146 in the Hb stabilizes the T state by forming a salt bridge with Asp94.
• Importance: The difference in pH between lung and metabolizing tissues ensures efficient oxygen transport.

Influence of pH on Oxygen Binding

• Versus pH:
  • High pH (low H+) indicates a greater affinity of hemoglobin for oxygen, promoting O2 binding.
  • Low pH (high H+) decreases affinity, facilitating oxygen release.
• Transition between States: The transition from T to R (relaxed) state is influenced by protonation and oxygen binding.

Carbon Dioxide Export from Metabolism

• CO2 Transport:
  • Approximately 15-20% of $CO_2$ is exported in the form of carbamate bound to hemoglobin; this process yields protons that contribute to the Bohr effect.
  • The remaining $CO2$ exists as bicarbonate ($HCO3^-$), which is formed by the action of carbonic anhydrase.

2,3-Bisphosphoglycerate's (BPG) Role

• Allosteric Regulation:
  • BPG decreases hemoglobin's affinity for $O_2$ by binding to the T state, stabilizing it.
  • The reaction:
    BPG + O2 ⇌ HbO2 + BPG
  • BPG binds in the central cavity between the beta subunits of deoxyhemoglobin, facilitating oxygen release.

Effects of Fetal and Adult Hemoglobin

• Fetal Hemoglobin (HbF):
  • Composed of α2γ2 which has a lower affinity for BPG but a higher affinity for oxygen than normal adult hemoglobin (α2β2).
• Adaptation to High Altitude:
  • Increased levels of BPG at high altitudes decrease hemoglobin's affinity for $O_2$, thus enhancing oxygen delivery to tissues under hypoxic conditions.

Mutations Affecting Hemoglobin Structure and Function

• Examples of Hemoglobin Variants:
  • Variants named after locations of discovery, affecting binding properties which can lead to disorders such as Methemoglobinemia and Sickle Cell Anemia.
• Sickle Cell Anemia:
  • Caused by a single amino acid substitution (Glu6 to Val6) in beta chains, leading to a polymerization of deoxygenated hemoglobin and sickling of red blood cells.
  • Provides some resistance to malaria in heterozygous individuals despite serious implications in homozygous cases.

Key Concepts and Comparisons

• Normal vs. Sickle Cell Hemoglobin:
  • Normal hemoglobin remains soluble while sickle cell hemoglobin becomes insoluble upon deoxygenation, causing aggregates.

Exam Preparation Notes

• Be sure to understand the mechanisms of the Bohr effect, the role of BPG, and the physiological functions of hemoglobin and myoglobin. Practice potential exam questions regarding the effects of pH, the transport functions of hemoglobin, and the implications of specific mutations.