Iron and Hemoglobin

• Iron in Hemoglobin

  • Essential for heme group functionality.

  • Iron exists in two oxidation states, particularly Fe2+.

• Structure

  • The heme group binds to oxygen and is influenced by surrounding carboxyl groups.

  • Proximity of positively charged groups aids in binding.

Myoglobin and Oxygen Binding

• Basics of Myoglobin

  • Myoglobin structure can be summarized in images to convey key concepts quickly.

  • Students are encouraged to actively engage with material, summarizing subjects from lectures.

• Concepts of Binding

  • Kd (Dissociation constant):

    • Kd indicates the affinity of binding.

    • Low Kd = high affinity for oxygen; high Kd = low affinity.

• Saturation

  • Defined as the ratio of myoglobin molecules bound to oxygen relative to the total amount of myoglobin present.

Hemoglobin vs. Myoglobin

• Overview

  • Hemoglobin consists of four subunits resembling myoglobin.

  • Distinct oxygen binding curves exist between hemoglobin and myoglobin.

• Allosteric Regulation

  • Factors like pH and CO2 concentration shift hemoglobin's saturation curve:

    • Decreased pH/ increased CO2 -> releases more oxygen.

  • Oxygen delivery is prolific in active tissues where CO2 is generated.

Mechanism of Hemoglobin Oxygen Binding

• Structural Changes

  • Binding of oxygen changes the structure of hemoglobin:

    • Iron position shifts, which pulls associated histidine and alters the subunit's conformation.

    • This alteration transmits through the protein, enriching overall oxygen binding.

• Animation Studies

  • Visual aids can demonstrate structural shifts when oxygen binds hemoglobin, enhancing understanding.

Cooperative Binding

• Sigmoidal Binding Curve

  • Illustrates cooperativity within hemoglobin subunits.

  • Positive cooperativity arises via structural changes that enhance binding.

• Bohr Effect

  • Increased CO2 and lower pH decrease oxygen affinity, promoting oxygen release where it’s needed.

Role of 2,3-BPG

• Mechanism of Action

  • 2,3-bisphosphoglycerate (2,3-BPG) binds hemoglobin, reducing oxygen affinity dramatically.

  • Important in preserving oxygen release to tissues under varying oxygen tension.

• Physiological Relevance

  • Elevation of 2,3-BPG occurs at high altitudes and during pregnancy, influencing oxygen transport efficiency.

Summary of Hemoglobin Functionality

• Oxygen Transport Dynamics

  • Hemoglobin transports oxygen from lungs to tissues, adjusting affinity dynamically based on physiological conditions.

• Energetics

  • CO2 and lactic acid from active tissues compete for protonation behavior, relevant to cellular respiration and energy metabolism.

Allosteric Effects in Proteins

• General Concept

  • Allosteric binding significantly governs protein behavior and interactions, critical in metabolic pathways.

• Examples

  • Oxygen and proton binding affects hemoglobin's conformation and function, essential in biochemistry and physiology.