๐ซ Respiration: Oxygen Transport & Bohr Dynamics
Respiratory gas exchange couples pulmonary alveolar diffusion with hemoglobin allosteric cooperative binding and systemic tissue delivery.
1. The Sigmoidal Oxygen-Hemoglobin Dissociation Curve
Hemoglobin ($Hb$) is a tetramer of two $alpha$ and two $beta$ globin subunits, each containing a heme prosthetic group with an $Fe^{2+}$ ion. Binding of oxygen to one heme induces a stereochemical quaternary transition from the low-affinity T-state (Tense) to the high-affinity R-state (Relaxed), producing positive cooperativity (Hill coefficient $n_H approx 2.8$).
2. Shifts in the $O_2$ Dissociation Curve (The Bohr Effect)
| Curve Direction | Physiological Triggers | Mechanism & Functional Consequence |
|---|---|---|
| Right Shift (Decreased Affinity / Facilitated $O_2$ Delivery) |
• ↑ $[H^+]$ / ↓ pH (acidosis) • ↑ $P_{CO2}$ (hypercapnia) • ↑ Temperature (fever, exercise) • ↑ 2,3-Bisphosphoglycerate (2,3-BPG) |
Stabilizes the deoxy T-state. At exercising skeletal muscle capillary beds ($P_{O2} approx 20text{ mmHg}$), hemoglobin readily unloads more oxygen to working tissues. $P_{50}$ increases from normal 26.6 mmHg. |
| Left Shift (Increased Affinity / Impaired $O_2$ Unloading) |
• ↓ $[H^+]$ / ↑ pH (alkalosis) • ↓ $P_{CO2}$ (hypocapnia) • ↓ Temperature (hypothermia) • ↓ 2,3-BPG • Fetal Hemoglobin ($HbF$: $alpha_2gamma_2$ binds 2,3-BPG poorly) |
Stabilizes the oxy R-state. Fetal hemoglobin left-shift enables the fetus to extract oxygen from maternal circulation across the placenta. $P_{50}$ decreases. |
3. Carbon Dioxide Transport Forms in Blood
- Dissolved $CO_2$ (~7%): Follows Henry’s law in plasma.
- Carbaminohemoglobin (~23%): $CO_2$ binds reversibly to terminal amino groups of globin polypeptides (forming carbamate residues). Deoxygenation of hemoglobin increases its affinity for $CO_2$ (Haldane Effect).
- Bicarbonate Ion ($HCO_3^-$, ~70%): Inside erythrocytes, $CO_2 + H_2O rightleftharpoons H_2CO_3 rightleftharpoons H^+ + HCO_3^-$ catalyzed by Carbonic Anhydrase (CA-II). $HCO_3^-$ is exported into plasma in exchange for incoming $Cl^-$ via the Band 3 anion exchanger (Chloride Shift / Hamburger Phenomenon).