Hemoglobin — structure & primary function

• Definition: Hemoglobin (Hb) is the red blood cell protein that transports O₂ and helps carry CO₂/H⁺.
• Structure: Tetrameric protein \(\alpha_2\beta_2\) (adult Hb); each subunit binds one O₂ at an iron center \(Fe^{2+}\).
• Other bindings: CO₂ forms carbaminohemoglobin; H⁺ is buffered by Hb; \(2,3\)-BPG binds Hb and lowers O₂ affinity.
• \(2,3\)-BPG: Produced in RBCs from glycolysis intermediates; increases with chronic hypoxia and promotes O₂ unloading.

Oxygen–hemoglobin dissociation curve (O₂–Hb curve)

• Shape & cooperativity: Sigmoidal curve due to cooperative O₂ binding across subunits; small PO₂ changes near physiological range cause large saturation changes.
• Right shift (promotes O₂ unloading): Caused by ↓pH (↑H⁺), ↑temperature, ↑CO₂, and ↑\(2,3\)-BPG; clinically means tissues get more O₂.
• Left shift (promotes O₂ loading): Caused by ↑pH, ↓temperature, ↓CO₂, ↓\(2,3\)-BPG, and presence of HbF; increases Hb O₂ affinity and reduces tissue unloading.
• Bohr effect: Local ↑CO₂ and H⁺ in tissues lower Hb affinity for O₂ (right shift), aiding O₂ release where needed.
• Haldane effect: In the lungs, O₂ binding to Hb reduces Hb affinity for CO₂ and H⁺, facilitating CO₂ release.

Fetal hemoglobin (HbF)

• Composition: \(\alpha_2\gamma_2\).
• Functional consequences: Higher O₂ affinity (left-shifted curve) because the γ subunits bind \(2,3\)-BPG poorly, promoting O₂ transfer from maternal blood to fetus.
• Clinical note: Hydroxyurea can induce HbF production and is used to treat sickle cell disease.

Myoglobin

• Role: O₂ storage in muscle; provides reserve in hypoxia.
• Properties: Single O₂ binding site (no cooperativity) and higher O₂ affinity than Hb (left-shifted), so it extracts O₂ from blood at low PO₂.

Key practical points for students

• Remember the major factors shifting the O₂–Hb curve: pH, temperature, CO₂, and \(2,3\)-BPG.
• Right shift = easier unloading to tissues; left shift = tighter O₂ binding (less unloading).
• Distinguish Bohr (CO₂/H⁺ effect on O₂ binding) from Haldane (O₂ effect on CO₂ binding).
• Hb composition matters: adult Hb \(\alpha_2\beta_2\), fetal Hb \(\alpha_2\gamma_2\), myoglobin single subunit.

Quick summary bullets

• Hb structure: \(\alpha_2\beta_2\), O₂ binds \(Fe^{2+}\).
• \(2,3\)-BPG lowers O₂ affinity; increases in chronic hypoxia.
• Bohr effect (tissues): ↑CO₂/H⁺ → right shift; Haldane (lungs): O₂ binding → CO₂ release.
• HbF: \(\alpha_2\gamma_2\), higher affinity; therapeutic induction by hydroxyurea.
• Myoglobin: single site, high affinity O₂ store.