Hemoglobin Structure and Types

Hemoglobin Structure and Types

• Red blood cells contain hundreds of thousands of hemoglobin molecules, responsible for transporting oxygen.
• Oxygen binds to heme, a component within the hemoglobin molecule.

Hemoglobin Structure

• Hemoglobin (Hb) is a spherical molecule comprising four peptide subunits (globins), forming a quaternary structure.
• Adult hemoglobin (Hb A) is a tetramer, composed of two alpha (α) and two beta (β) globins.
• Each globin subunit contains one heme group with a central iron (Fe²⁺) ion.

Heme Structure

• Heme is a Fe-porphyrin compound.
• Porphyrins are cyclic compounds formed by fusing four pyrrole rings linked by methenyl bridges (=CH-).
• The pyrrole rings are labeled I, II, III, and IV, and bridges as alpha, beta, gamma, and delta.
• The presence of an iron atom makes heme a ferroprotoporphyrin.

Hemoglobin Derivatives

• Hemoglobin readily reacts with other substances.
• Oxyhemoglobin: An unstable and reversible compound where iron remains in the ferrous (Fe²⁺) state.
• Reduced/Deoxygenated hemoglobin: Oxygen is released from oxyhemoglobin.
• Carbaminohemoglobin: Binds with carbon dioxide.
• Carboxyhemoglobin: Binds with carbon monoxide (CO); CO has a much higher affinity for hemoglobin than oxygen.
• Methemoglobin: Iron is oxidized to ferric (Fe³⁺), preventing the reversible binding of oxygen.
• Glycosylated hemoglobin (HbA1c): Glucose attaches to terminal valine in the beta (β) chains; elevated levels indicate diabetes mellitus.

Physiological Varieties of Hemoglobin

• Fetal hemoglobin (HbF): Found in fetal red blood cells, it has a higher affinity for oxygen than adult hemoglobin; it disappears within 2-3 months after birth
• Its globin part consists of two alpha (α) and two gamma (γ) polypeptide chains in place of two beta (β) chains.

Hemoglobin Functions

• Transport of Respiratory Gases: Carries oxygen from lungs to tissues, and carbon dioxide from tissues to lungs.
• Major Blood Buffer: Hemoglobin's histidine residues contribute substantially to blood pH regulation
• Other Functions: Changes in hemoglobin structure can lead to various disorders (e.g., sickle cell anemia, thalassemia, methemoglobinemia).

Hemoglobin Synthesis-Factors Controlling

• Role of Proteins: Amino acids from protein sources are required for globin synthesis. Low protein intake hinders globin regeneration
• Role of Iron: Essential for heme synthesis. Iron recycled from old red blood cells is also reused.
• Role of other Metals (e.g,, Copper): Required for proper iron absorption and mobilization.

Fate of Hemoglobin

• Hemoglobin is broken down, releasing globin and iron components.
• Release of amino acids for reuse and bilirubin that is metabolized. The Iron is stored as ferritin or transferred to the bone marrow for reuse.

Myoglobin

• Myoglobin (Mb) is a monomeric oxygen-binding hemoprotein found in heart and skeletal muscle, serving as an oxygen reservoir. It has a single polypeptide chain with a heme moiety.

Hemoglobin Structure-Quaternary Structure

• There are two alternate conformations of Hemoglobin's Quaternary Structure
• The T-State (Tense): Has low affinity for oxygen; deoxy state
• The R-State (Relaxed): Has higher affinity for oxygen; oxy state
• These conformations shift based on oxygen binding and allosteric factors.

Structure of Globin

• Globin is made of four polypeptide chains: two alpha (α) chains and two beta (β) chains
• Each alpha chain contains 141 amino acids, each beta chain contains 146 amino acids
• Normal adult hemoglobin A is written as α₂β₂.

Red Blood Cell (RBC) Lifespan

• The average lifespan of red blood cells is about 120 days.
• Conditions that reduce lifespan include hereditary and extracorpuscular defects, as well as deficits in red blood cell enzymes.

Organs Involved in Heme Synthesis

• The variable organs involved in heme synthesis include reticuloendothelial cells, typically found in various sites like the liver

Hemoglobin Levels

• Normal hemoglobin levels (g/dL): Male 14-18; Female 12-15.5
• Levels can vary based on age and physiological state (e.g., pregnancy).