Hemoglobin Structure and Types

Hemoglobin

• A red pigment found within red blood cells (RBCs)
• Molecular weight of about 65,000
• Concentration varies based on sex and age
  • Males: 14-18 g/dl
  • Females: 12-16 g/dl
  • Neonates: 14-20 g/dl

Hemoglobin Structure

• Composed of two parts:
  • Heme: A porphyrin ring with iron in its reduced state. Synthesized from glycine and succinyl-CoA.
  • Globin: Four polypeptide chains (α, β, γ, δ)
• Each subunit of hemoglobin contains one heme and one polypeptide chain.
• Hb = 4 heme + 4 polypeptide chains

Oxyhemoglobin and Deoxyhemoglobin

• Oxyhemoglobin: Hemoglobin bound to oxygen. Typically appears pink.
• Deoxyhemoglobin: Hemoglobin without oxygen. Typically appears blue.

Types of Normal Hemoglobin

• Hb A: Most common type in adults. Composed of 2 α and 2 β chains, forming 98% of total hemoglobin.
• Hb A2: Present in adults. Composed of 2 α and 2 δ chains, forming 2% of total hemoglobin.
• Hb F: Hemoglobin found in fetuses. Composed of 2 α and 2 γ chains. Has a higher affinity for oxygen compared to Hb A.

Red Blood Cell Turnover

• Life span of an RBC: 120 days.
• Destruction occurs primarily in the spleen, liver, and bone marrow.

Reactions of Hemoglobin

• Hemoglobin + O₂ → Oxyhemoglobin
• Hemoglobin – O₂ → Deoxyhemoglobin
• Hemoglobin + glucose → Glycosylated hemoglobin (Hb A1c)
• Hb A1c is important for monitoring diabetes in patients.

Abnormal Hemoglobin Variants

• Abnormalities primarily affect the globin part of the molecule.
• Hemoglobin S: Glutamic acid at position 6 of the β chain is replaced by valine.
  • This change results in reduced solubility and easy precipitation, especially in low oxygen environments.
  • Precipitation causes red cells to sickle, shortening their lifespan.
  • Severity depends on whether one or both β chains are affected:
    • One chain: Sickle cell trait (mild)
    • Two chains: Sickle cell anemia (severe)
  • Hb S is prevalent in Africa, especially in Western Sudan.

Thalassaemia

• Absence of a whole chain (either α or β).
• α Thalassaemia: One or two α chains are missing.
• β Thalassaemia: One or two β chains are missing.
• Thalassemia is common in the Mediterranean region.

Red Blood Cell Breakdown

• Red blood cells are destroyed after approximately 120 days.
• Hemoglobin is released during breakdown.
• The cell membrane is digested by phagocytes.

Fate of Hemoglobin

• Splits into heme and globin.
• Globin is broken down into amino acids, which can be reused for protein synthesis.
• Heme:
  • Iron is recycled by transferrin and used in new hemoglobin synthesis.
  • Porphyrin is converted to biliverdin.

Bilirubin

• Biliverdin is converted to bilirubin, a yellow pigment not soluble in water.
• Excretion of bilirubin:
  • Bilirubin becomes soluble through conjugation with glucuronic acid in the liver.
  • Conjugated bilirubin enters the small intestine through bile.

Intestinal Bilirubin Metabolism

• In the intestine, conjugated bilirubin is converted into urobilinogen (stercobilinogen).
• Most urobilinogen is reabsorbed in the terminal ileum.
• The remaining urobilinogen is excreted in feces, giving it its natural color.

Absorbed Urobilinogen

• Water-soluble
• Transported to the liver and re-excreted through bile.
• Can be filtered by the kidneys and excreted in urine.

Enterohepatic Circulation

• The recycling of bilirubin between the liver and the intestines.

Jaundice

• A condition characterized by yellowing of the skin and whites of the eyes.
• Caused by a buildup of bilirubin in the blood.
• Normal bilirubin levels:
  • Adult: 0.2-1.0 mg/dL
  • Neonates (first few days): 2.0-6.0 mg/dL
  • Levels above this can indicated liver disease or impaired bilirubin breakdown.

Explore the fascinating world of hemoglobin, the red pigment in red blood cells. This quiz covers its molecular structure, types, and differences between oxyhemoglobin and deoxyhemoglobin, along with its concentration variations. Test your knowledge on this critical component of human physiology.