Hemoglobin and Myoglobin Lecture Notes

Overview of Protein Structure

• Proteins are made from amino acids.
• Folding: Primary -> Secondary (α-helices & β-sheets) -> Tertiary -> Quaternary structure.

Introduction to Hemoglobin and Myoglobin

• Chosen because they were the first protein structures determined and are well-studied.
• Function: Oxygen carriers.

Hemoglobin

• Location: Transport molecule for oxygen in the blood.
• Structure: Tetrameric protein with 4 subunits: 2 α and 2 β.
  • Each subunit has a heme group and iron.
• Oxyhemoglobin: Hemoglobin bound with oxygen.
• Deoxyhemoglobin: Hemoglobin without oxygen.

Myoglobin

• Location: Oxygen storage in tissues.
• Structure: Monomeric protein, stops at the tertiary structure.
  • Contains 8 α-helices and a heme group.
• Function: Binds and stores oxygen, released when oxygen levels are low.

Heme Group

• Composition: Has an iron (Fe2+) atom bound to four nitrogens.
• Oxygen Binding: Oxygen binds to iron, stabilized by hydrogen bonding with histidine residues.
  • Proximal histidine: Binds to iron.
  • Distal histidine: Stabilizes bound oxygen through hydrogen bonds.

Structural Similarities

• Comparison: Myoglobin structure is similar to the α1 subunit of hemoglobin.

Oxygen Binding Curves

Myoglobin

• Curve: Hyperbolic.
• Affinity: Binds tightly to oxygen until it’s very low.

Hemoglobin

• Curve: Sigmoidal (S-shaped).
• Affinity: High at high oxygen concentration, decreases at low concentrations.

Functional Implications

• Hemoglobin: Transports oxygen; binds in lungs (high O2) and releases it in tissues (low O2).
• Myoglobin: Stores oxygen; releases it only during low oxygen conditions.

Positive Cooperativity

• Definition: One O2 binding increases affinity for another O2 to bind.
• T (Tense) form: Deoxyhemoglobin, low O2 affinity.
• R (Relaxed) form: Oxyhemoglobin, high O2 affinity.
  • Conformational Changes: Binding of O2 causes hemoglobin to shift from T to R form, increasing O2 affinity.

Allosteric Interactions

• Definition: Molecules bind to protein and modulate activity.
• Oxygen: Key allosteric regulator for hemoglobin.
• Others: 2,3-Bisphosphoglycerate (2,3-BPG), CO2, and H+.

pH and CO2

• Carbon Dioxide: CO2 + H2O ↔ HCO3- + H+
• Bohr Effect: Lower pH (higher H+) decreases O2 affinity, shifting the hemoglobin curve.

2,3-Bisphosphoglycerate (2,3-BPG)

• Function: Reduces hemoglobin's O2 affinity by stabilizing the T form.
• Differences: Fetal hemoglobin has a lower affinity for 2,3-BPG.

Carbon Monoxide Poisoning

• Binding: CO binds to hemoglobin with high affinity, forming carboxyhemoglobin.
• Effect: Shifts hemoglobin binding curve, reduces O2 release to tissues.
  • Consequence: Tissues may suffer from O2 deprivation despite adequate O2 transport.