Unlike myoglobin, which binds oxygen independently, hemoglobin (Hb) exhibits allosteric kinetics. This means the binding of oxygen at one site affects the binding affinity at other sites within the same tetramer.
1. Positive Cooperativity
Hemoglobin is a tetramer (α2 β2). When the first oxygen molecule binds to one heme group, it triggers a conformational change that is transmitted to the other three subunits, increasing their affinity for oxygen.
- T-State (Tense): Deoxyhemoglobin; low affinity for O2.
- R-State (Relaxed): Oxyhemoglobin; high affinity for O2.
The transition from T to R state is the "switch" that drives the rapid loading of oxygen in the lungs.
2. The Sigmoid Dissociation Curve
The relationship between the partial pressure of oxygen (PO2) and the percentage saturation of Hb is represented by a Sigmoidal Curve. This shape is physiologically crucial:
| Region | Kinetics & Effect |
|---|---|
| Steep Portion (20-40 mmHg) | Small changes in PO2 lead to large releases of O2. This occurs at the tissue level. |
| Plateau Region (>70 mmHg) | Hb remains almost fully saturated even if PO2 drops slightly. This occurs in the lungs. |
3. Hill Equation & Coefficient
The degree of cooperativity is measured by the Hill Coefficient (n). For a perfectly non-cooperative protein (like Myoglobin), n = 1. For Hemoglobin, n approx 2.8 to 3.0. This value indicates strong positive cooperativity between the subunits.
The degree of saturation ($Y$) as a function of the partial pressure of oxygen ($P_{O_2}$):
$$Y = \frac{(P_{O_2})^n}{(P_{O_2})^n + (P_{50})^n}$$$n$ (Hill Coefficient): Represents the degree of cooperativity.
$P_{50}$: The partial pressure at which 50% of the sites are saturated.
4. Factors Shifting the Kinetics (Allosteric Effectors)
The affinity can be shifted by metabolic byproducts, described by the Bohr Effect:
- Right Shift (Lower Affinity): Increased CO2, increased acidity (low pH), increased temperature, and increased 2,3-BPG. This helps unload O2 to working muscles.
- Left Shift (Higher Affinity): Decreased CO2, higher pH, and lower temperature. This helps load O2 in the lungs.
Comparative Kinetics: Hb vs. Mb
The difference in oxygen affinity is clearly visible in their dissociation curves. Myoglobin (Mb) acts as a storage reservoir, while Hemoglobin (Hb) acts as a smart delivery system.
| Property | Myoglobin | Hemoglobin |
|---|---|---|
| Kinetics | Non-cooperative | Cooperative (Allosteric) |
| Curve | Hyperbolic | Sigmoidal |
| Hill Coeff (n) | n = 1.0 | n ≈ 2.8 |
Chhatrapati Shahu Ji Maharaj University Kanpur M.Sc. Semester-III 2013 & 2018