Hemoglobin and Myoglobin Functions Quiz

Oxygen-Carrying Proteins

• Hemoglobin is the most abundant protein in red blood cells, efficiently transporting oxygen from the lungs to tissues and carbon dioxide and hydrogen ions back to the lungs.
• Myoglobin is found in muscle, providing a reserve oxygen supply when needed.
• Both proteins bind oxygen due to a prosthetic group called heme (or haem).

The Heme Group

• Heme consists of a complex organic ring structure (protoporphyrin) with a single iron atom in its ferrous (Fe²⁺) state.
• The iron atom can be in either ferrous (Fe²⁺) or ferric (Fe³⁺) oxidation state; only the ferrous state binds oxygen.

Oxygen Binding to Heme

• The iron ion forms two additional bonds on each side of the heme plane, called the 5^th and 6^th coordination sites.
• The 5^th site is bound by the imidazole ring of a histidine residue (proximal histidine).
• Oxygen binds at the 6^th coordination site.
• Oxygen binding alters hemoglobin's magnetic properties, which is used in fMRI.

Myoglobin Structure

• Myoglobin is a single polypeptide chain.
• His E7 is the distal His.
• His F8 is the proximal His.

Ligand Binding Principles

• The reversible binding of a protein (P) to a ligand (L) can be described by a simple equilibrium expression: P + L ⇌ PL
• The reaction has an equilibrium constant (K_a).
  • K_a = [PL] / ([P] [L]) = [PL]/([P] [L])

Fraction of Ligand Binding Sites Occupied

• The fraction (θ) is the number of ligand binding sites on the protein that are occupied by ligand.
  • θ = [PL]/([PL] + [P]) = K_a[L] / ([L] + K_a)

Oxygen Binding to Myoglobin

• The partial pressure of oxygen (pO₂) is used to determine the amount of myoglobin that binds to oxygen at various levels in the fractional saturation (θ)
  • θ = pO₂ / (pO₂ + P₅₀)
• P₅₀ is the partial pressure of oxygen at which the protein is half saturated

Myoglobin vs. Hemoglobin

• Myoglobin (Mb) and hemoglobin (Hb) are closely related proteins with nearly identical oxygen-binding structures.
• Mb exists as a single polypeptide, while Hb has four polypeptide chains (two α-subunits and two β-subunits).
• Both have significant sequence and structural homology.

Hemoglobin Subunits Form Tetramers

• Hemoglobin subunits interact to create a quaternary structure.
• Myoglobin structure differences lead to monomers vs hemoglobin tetramers.

Oxygen Binding to Hemoglobin

• The oxygen binding curve for hemoglobin is sigmoidal in shape.
• The binding of oxygen at one site increases the likelihood that oxygen will bind at other sites.
• Oxygen unloading at one site facilitates oxygen unloading at other sites (cooperativity).
• The allosteric effect of hemoglobin is caused by differing interactions between the 4 globin chains and their oxygen binding sites.

Cooperative binding/Bohr effect (for Hemoglobin)

• Binding and release of O₂ in Hb is affected by pH and CO₂.
• High CO₂ levels decrease blood pH, and the binding of CO₂ to protein amino groups facilitates oxygen release in tissues.
• This CO₂ mediated effect on oxygen affinity is called the Bohr effect.

Oxygen Binding to Hb - 2,3-BPG

• 2,3-BPG (2,3-bisphosphoglycerate) greatly reduces Hb's affinity for oxygen.
• 2,3-BPG is important for adaptations in high-altitude conditions and hypoxia.
• The concentration of 2,3-BPG in red blood cells increases in people suffering from hypoxia.

Fetal Hemoglobin

• Fetal hemoglobin (HbF) has a higher affinity for oxygen than adult hemoglobin (HbA).
• The difference in amino acid sequence in the fetal globin chains helps maintain oxygen delivery from mother to child.

Temporal Expressions of Globin Chains

• The production of different hemoglobin types shifts throughout a child's development.

Hemoglobinopathies

• Hemoglobinopathies are a group of inherited disorders that affect hemoglobin production or structure.
• Sickle-cell anemia results from the aggregation of mutated deoxyhemoglobin molecules, often caused by a point mutation leading to a hydrophobic region on the protein.
• Thalassemia is an inherited disease caused by a loss or substantial reduction of a specific hemoglobin chain, leading to a lack of functional hemoglobin.

Summary of Key Concepts

• Understand the differences and similarities between myoglobin and hemoglobin.
• Learn how carbon monoxide (CO), carbon dioxide (CO₂), and 2,3-BPG affect the oxygen-binding capacity of hemoglobin.
• Be prepared to analyze oxygen-binding curves regarding affinity, P₅₀, and oxygen release.
• Understand the Bohr effect and the influence of pH and CO₂.
• Grasp how 2,3-BPG regulates oxygen binding and its relevance in physiological adaptations.
• Understand the functional and structural differences between fetal and adult hemoglobin.
• Note the different hemoglobin expression patterns during development.