Overview of Haemoglobins
Haemoglobin is a vital protein found in red blood cells that is responsible for transporting oxygen from the lungs to tissues and facilitating the return of carbon dioxide from tissues to the lungs for exhalation. It plays a critical role in maintaining tissue oxygenation and overall metabolic function.
Structure of Haemoglobin
- Haemoglobin is a tetrameric protein composed of four subunits:
- Each subunit contains a heme group and a globin chain.
- Heme group: A porphyrin ring with an iron (Fe2+) ion at its centre, capable of binding one molecule of oxygen (O2).
- Globin chains: Polypeptide chains that provide structural support and help regulate oxygen binding and release.
- The most common form of haemoglobin in adults is Haemoglobin A (HbA), composed of two alpha (α) and two beta (β) globin chains (α2β2).
Types of Haemoglobin
- Haemoglobin A (HbA):
- Composed of two alpha and two beta chains (α2β2).
- Accounts for approximately 97% of adult haemoglobin.
- Haemoglobin A2 (HbA2):
- Composed of two alpha and two delta chains (α2δ2).
- Accounts for about 2-3% of adult haemoglobin.
- Haemoglobin F (HbF) (Fetal Haemoglobin):
- Composed of two alpha and two gamma chains (α2γ2).
- Predominant form of haemoglobin in the fetus and newborns, with a higher affinity for oxygen than adult haemoglobin.
- Gradually replaced by HbA after birth.
- Abnormal Haemoglobins:
- Haemoglobin S (HbS): Associated with sickle cell disease, resulting from a mutation in the beta chain.
- Haemoglobin C (HbC): Results from a different mutation in the beta chain, leading to haemoglobin C disease.
- Thalassemias: Genetic disorders characterized by reduced or absent production of one of the globin chains.
Function of Haemoglobin
- Oxygen Transport:
- Haemoglobin binds oxygen in the lungs, where oxygen concentration is high, forming oxyhaemoglobin (HbO2).
- Oxygen is released in tissues where oxygen concentration is low, facilitating cellular respiration.
- Carbon Dioxide Transport:
- Haemoglobin helps transport carbon dioxide (CO2) from tissues to the lungs for exhalation.
- CO2 binds to the amino groups of the globin chains, forming carbaminohaemoglobin.
- Buffering:
- Haemoglobin acts as a buffer by binding hydrogen ions (H+) and helping maintain blood pH within a narrow range.
Oxygen-Haemoglobin Dissociation Curve
- The oxygen-haemoglobin dissociation curve is a sigmoidal graph that describes the relationship between the partial pressure of oxygen (pO2) and haemoglobin saturation with oxygen.
- Right Shift:
- Indicates decreased affinity of haemoglobin for oxygen, facilitating oxygen release to tissues.
- Caused by increased CO2, increased H+ (lower pH), increased temperature, and increased 2,3-bisphosphoglycerate (2,3-BPG).
- Left Shift:
- Indicates increased affinity of haemoglobin for oxygen, facilitating oxygen binding in the lungs.
- Caused by decreased CO2, decreased H+ (higher pH), decreased temperature, and decreased 2,3-BPG.
Clinical Relevance
- Anaemias:
- Conditions characterized by a decrease in the number of red blood cells or haemoglobin, leading to reduced oxygen-carrying capacity.
- Causes include nutritional deficiencies (iron, vitamin B12, folate), genetic disorders (thalassemias, sickle cell disease), and chronic diseases.
- Haemoglobinopathies:
- Genetic disorders affecting the structure or production of haemoglobin, such as sickle cell disease and thalassemias.
- Lead to various clinical complications, including anaemia, pain, and organ damage.
- Carbon Monoxide Poisoning:
- Carbon monoxide (CO) binds to haemoglobin with a much higher affinity than oxygen, forming carboxyhaemoglobin and reducing oxygen delivery to tissues.
- Symptoms include headache, dizziness, confusion, and, in severe cases, death.
- Methaemoglobinemia:
- A condition where iron in the heme group is oxidized to Fe3+, forming methaemoglobin, which cannot bind oxygen effectively.
- Causes include genetic mutations, exposure to certain drugs or chemicals, and nitrate-contaminated water.
Summary
Haemoglobin is an essential protein in red blood cells, responsible for oxygen and carbon dioxide transport, as well as buffering blood pH. It has a complex structure that allows it to perform these functions effectively. Variations in haemoglobin structure and function can lead to various clinical conditions, highlighting its critical role in human physiology and health.