Haemoglobin Structure and Function

Haemoglobin Structure and Function

• Haemoglobin (Hb) is a protein in red blood cells that carries oxygen.
• Each Hb molecule consists of four polypeptide chains.
• Each polypeptide chain is attached to a heme group.
• An iron atom (Fe²⁺) is at the centre of each heme group.
• Iron binds to oxygen, allowing Hb to transport oxygen.

Co-operative Binding

• Binding of one oxygen molecule to Hb causes a conformational change in the second polypeptide chain.
• Increasing the affinity for the next oxygen molecules to bind.
• The binding of oxygen to Hb is a cooperative process.
• The fourth oxygen molecule has a much higher affinity than the first.
• This cooperative binding allows Hb to efficiently load and unload oxygen in different parts of the body.

Types of Haemoglobin

• Haemoglobin A (HbA): 95-98% in adult blood.
  • Composed of two alpha and two beta polypeptide chains (α₂β₂).
• Haemoglobin A2 (HbA2): 1.5-3% in adult blood.
  • Composed of two alpha and two delta chains (α₂δ₂).
• Foetal haemoglobin (HbF): present at birth, up to 80% of Hb at birth.
  • This haemoglobin has a greater affinity for oxygen than HbA, aiding oxygen transfer from mother to foetus.
  • Composed of two alpha and two gamma chains (α₂γ₂).
• Embryonic haemoglobins (Gower 1 & Gower 2): these are transient forms.

Haemoglobin Breakdown

• Old or damaged red blood cells (RBCs) are broken down by macrophages in the spleen.
• Haemoglobin is broken down into heme and globin.
• Globin is broken down into amino acids and reused.
• Heme is converted to bilirubin, a yellow pigment.
• Bilirubin is transported to the liver and excreted in bile.
• A buildup of bilirubin can cause jaundice (yellowing of the skin and eyes).

Haemoglobin Levels

• The World Health Organization (WHO) defines anaemia as a Hb level below 7.7 mmol/L (13 g/dL) in men, and below 7.4 mmol/L (12 g/dL) in women.
• The number of red blood cells (RBC) and the concentration of haemoglobin in these cells are crucial measurements.

Haemoglobinopathies

• Haemoglobinopathies are inherited disorders that result in abnormal haemoglobin production.
• Approximately 5% of the global population has a globin variant.
• Some types include:
  • Abnormal polypeptide chains (HbC, HbE, HbS).
  • Chains produced in decreased amounts or absent (α or βthalassemia).

Haemoglobin S

• HbS is a type of abnormal haemoglobin.
• Characterized by a single amino acid substitution in the beta chain (valine instead of glutamic acid).
• At low oxygen concentrations, HbS changes into a fibrous material, causing red blood cells to distort in shape (sickling).
• Sickled red blood cells obstruct blood flow, cause intense pain, severe anaemia, and can increase the risk of stroke.

Case Studies

• Provided case studies in the notes depict examples of clinical presentation of haematological conditions based on patient history, physical examination findings, and a full blood count (FBC)

Iron Profile

• Serum ferritin: storage form of iron; low levels may point to iron deficiency.
• Serum iron: amount of iron bounded to transferrin. Levels measured to determine iron deficiency.
• Total Iron Binding Capacity (TIBC): total amount of transferrin, reflecting the capacity available for iron binding.
• Transferrin saturation: percentage of transferrin protein that is occupied by iron.

Explore the intricate structure and essential functions of haemoglobin in this quiz. Learn about the cooperative binding of oxygen and the different types of haemoglobin found in the human body. Test your understanding of how haemoglobin adapts to various physiological conditions.